RU2845591C1 - PYRAZOLO [1,5-α]PYRIMIDINE DERIVATIVES HAVING MULTIMODAL ACTIVITY AGAINST PAIN - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to a compound of general formula (I) wherein m is 1, 2, 3 or 4; n is 1 or 2; t is 0 or 1; X is selected from a group consisting of a bond, -[CH₂]_p-, -[CH₂]_pNR_x[CH₂]_q-, -[CH₂]_pO[CH₂]_q-, -[CH₂]_pNR_xC(O)[CH₂]_q- and -[CH₂]_pNR_xCH(CH₃)-; where p is 0, 1, 2, 3 or 4; q is 0, 1, 2, 3 or 4; R_x is selected from the group consisting of hydrogen, unsubstituted C_1-6alkyl and C_1-6alkyl substituted with one or more halogen atoms; R₁ is selected from the group presented in the claims; R₆ is selected from the group of radicals indicated in the claims; R₆' is selected from the group consisting of hydrogen and unsubstituted C_1-6alkyl; alternatively R₆ and R₆' taken together with the nitrogen atom to which they are bonded form the structure given in the claims, wherein said heterocyclyl in the case of substitution is substituted with one or more substituents selected from -R₁₄, -[CH₂]_rOR₁₄, =O, -[CH₂]_rNR₁₄R₁₄', S(O)₂R₁₄, -CN, -C(O)R₁₄ and -C(O)NR₁₄R₁₄'; where R₁₄ and R₁₄' are independently selected from hydrogen and unsubstituted C_1-6alkyl; R₂ is selected from the group consisting of hydrogen, unsubstituted C_1-6alkyl, unsubstituted C_3-7cycloalkyl, unsubstituted C_1-6alkylC_3-7cycloalkyl, halogen and -OR₇; R₇ is selected from the group consisting of hydrogen and unsubstituted C_1-6alkyl; R₃ is selected from the group consisting of hydrogen and unsubstituted C_1-6alkyl; R₄ is selected from the group consisting of structures given in the claims; where the phenyl in R₄ in the case of substitution is substituted with one or more substituents selected from halogen, -R₄₁, -[CH₂]_rOR₄₁, –CN and halogen C_1-6alkyl; where R₄₁ is selected from hydrogen and unsubstituted C_1-6alkyl; where heterocyclyl in R₄ in case of substitution is substituted with one haloC_1-6alkyl; R₅ and R₅' are independently selected from the group consisting of hydrogen, unsubstituted C_1-6alkyl and C_1-6alkyl substituted with one substituent- OH; where r is 0, 1, 2 or 3. Invention also relates to a compound of formula (I), where R₁ is a group given in the claims; where R₁₁ and R₁₁' are independently selected from the structures given in the claims, wherein said heterocyclyl is unsubstituted or substituted with one R₂₁ or -[CH₂]_rNR₂₁R₂₁', where R₂₁ and R₂₁' are independently selected from hydrogen and unsubstituted C_1-6 alkyl; where r is 0, 1, 2 or 3; and X, R₂, R₃, R₄, R₅, R₅', m, n and t are as defined in claim 1. Invention also relates to a method of producing a compound of formula (I), use of compounds of formula (Ia), (Ib), (IIa), (IIb), (IIIa), (IIIb), (IV), (V), (VI), (VII), (VIII), (IX), (X) or (XI) to obtain compounds of formula (I) and a pharmaceutical composition based on a compound of formula (I) having bidirectional binding activity with the subunit α₂δ-1 voltage-dependent calcium channels and with sigma-1 receptor (σ1).

EFFECT: compounds possessing bidirectional inhibiting activity with respect to α₂δ-1 subunit of voltage-dependent calcium channel and σ1-receptor for treating pain.

17 cl, 25 tbl, 253 ex

Description

The present invention relates to compounds having bidirectional pharmacological activity towards both the _α2δ subunit of voltage-dependent calcium channels and the sigma-1 (σ1) receptor. More particularly, the present invention relates to pyrazolo[1,5-a]pyrimidine derivatives having this pharmacological activity, to methods for preparing such compounds, to pharmaceutical compositions containing them, and to their use in therapy, in particular in the treatment of pain.

BACKGROUND OF THE INVENTION

Adequate pain control is an important challenge because currently available treatments in many cases provide only minor improvements, leaving many patients without pain (Turk DC, Wilson HD, Cahana A. Lancet, 2011, 377, 2226-2235). Pain affects a significant proportion of the population with an estimated prevalence of 20%, and its prevalence, particularly in the case of chronic pain, is increasing due to the ageing population. In addition, pain is clearly associated with comorbidities such as depression, anxiety and insomnia, resulting in significant productivity losses and socioeconomic burden (Goldberg DS, McGee SJ, BMC Public Health, 2011, 11, 770). Current pain management options include nonsteroidal anti-inflammatory drugs (NSAIDs), opioid agonists, calcium channel blockers, and antidepressants, but they are suboptimal due to their safety profile. All of them show limited efficacy and a number of secondary effects that hinder their use, especially in chronic conditions.

Voltage-gated calcium channels (VGCCs) are essential for a variety of key functions in the body. Different subtypes of voltage-gated calcium channels have been described (Zamponi et al.; Pharmacol. Rev. 2015, 67, 821–70). VGCCs are assembled by interactions of different subunits, namely α ₁ (Ca _v α ₁ ), β (Ca _v β) α ₂ δ (Ca _v α ₂ δ), and γ (Ca _v γ). The α ₁ subunits are the key pore-forming units of the channel complex, responsible for Ca ²⁺ conduction and mediating Ca ²⁺ uptake. The _α2δ , β, and γ subunits are accessory, although they are critical for channel regulation because they upregulate the expression of _α1 subunits in the plasma membrane and also modulate their function, resulting in functional diversity in different cell types. Based on their physiological and pharmacological properties, VGCC can be divided into low-voltage-activated T-type (Ca _v 3.1, Ca _v 3.2, and Ca _v 3.3) and high-voltage-activated L-type (Ca _v 1.1-Ca _v 1.4), N-type (Ca _v 2.2), P/Q-type (Ca _v 2.1), and R-type (Ca _v 2.3), depending on the Ca _v α subunits that form the channel. All of these five subclasses are found in the central and peripheral nervous systems. Regulation of intracellular calcium by activation of these VGCCs plays an indispensable role in 1) neurotransmitter release, 2) membrane depolarization and hyperpolarization, 3) enzyme activation and deactivation, and 4) gene regulation (Perret and Luo, Neurotherapeutics 2009, 6, 679-92; Zamponi et al., 2015 supra; Neumaier et al., Prog. Neurobiol. 2015, 129, 1-36). A large body of evidence clearly indicates that VGCCs are involved in mediating various disease states, including pain modulation. Drugs interacting with different calcium channel subtypes and subunits have been developed. Current therapeutics include drugs targeting the L-type calcium channel Ca _v 1.2, in particular 1,4-dihydropyridines, which are widely used in the treatment of hypertension. T-type calcium channels (Ca _v 3) are the target of ethosuximide, which is widely used in absence epilepsy. Ziconotide, a peptide blocker of N-type calcium channels (Ca _v 2.2), has been approved for the treatment of intractable pain (Perret and Luo, 2009, supra; Vink and Alewood, Br. J. Pharmacol. 2012, 167, 970–89).

The Ca _v 1 and Ca _v 2 subfamilies contain an accessory subunit, α ₂ δ, which is a therapeutic target for gabapentin-like drugs used in some types of epilepsy and chronic neuropathic pain. There are currently four known α ₂ δ subunits, each encoded by a separate gene, all of which contain splice variants. Each α ₂ δ protein is encoded by a single messenger RNA and is post-translationally cleaved and then cross-linked by disulfide bonds. Four genes encoding α ₂ δ subunits have now been cloned. α ₂ δ-1 was originally cloned from skeletal muscle and has a fairly widespread distribution. Subsequently, α ₂ δ-2 and α ₂ δ-3 subunits were cloned from brain. The most recently identified subunit, α ₂ δ-4, is predominantly non-neuronal. The protein sequence of human α ₂ δ-4 shares 30, 32, and 61% identity with the human α ₂ δ-1, α ₂ δ-2, and α ₂ δ-3 subunits, respectively. The genetic structure of all α ₂ δ subunits is similar. All α ₂ δ subunits are characterized by several splice variants (Davies et al., Trends Pharmacol Sci. 2007, 28, 220-8.; Dolphin AC, Nat Rev Neurosci. 2012, 13, 542-55, Biochim. Biophys. Acta 2013, 1828, 1541-9).

The Ca _v α ₂ δ-1 subunit may play an important role in the development of neuropathic pain (Perret and Luo, 2009, supra; Vink and Alewood, 2012, supra). Biochemical data indicated a significant upregulation of the Ca _v α ₂ δ-1 subunit, but not Ca _v α ₂ δ-2, in the dorsal horn and DRG after nerve injury, which correlates with the development of neuropathic pain. Furthermore, blocking axonal transport of injury-induced DRG Ca _v α ₂ δ-1 subunit to central presynaptic terminals reduces tactile allodynia in nerve-injured animals, indicating that increased amounts of Ca _v α ₂ δ-1 subunit in the DRG mediate neuropathic allodynia.

The Ca _v α ₂ δ-1 subunit (and Ca _v α ₂ δ-2, but not the Ca _v α ₂ δ-3 and Ca _v α ₂ δ-4 subunits) is the binding site for gabapentin, which has antiallodynic/hyperalgesic effects in patients and animal models. Since injury-induced Ca _v α ₂ δ-1 expression correlates with neuropathic pain, its development and maintenance, and various calcium channels are known to mediate synaptic neurotransmission in the spinal cord and neuronal excitability in the DRG, injury-induced upregulation of the Ca _v α ₂ δ-1 subunit may mediate the initiation and maintenance of neuropathic pain by altering the properties and/or distribution of VGCC in a subset of neurons in the DRG and their central terminals and, consequently, modulate excitability and/or synaptic plasticity in the dorsal horn. Intrathecal administration of antisense oligonucleotides against the Ca _v α ₂ δ-1 subunit can block nerve injury-induced Ca _v α ₂ δ-1 upregulation and prevent the onset of allodynia and relieve established allodynia.

As mentioned above, the α ₂ δ subunits of VGCC form a binding site for gabapentin and pregabalin, which are structural derivatives of the inhibitory neurotransmitter GABA, although they do not bind to GABAA, GABAB, or benzodiazepine receptors and do not alter GABA regulation in animal brain preparations. Binding of gabapentin and pregabalin to the Ca _v α ₂ δ subunit results in decreased calcium-dependent release of numerous neurotransmitters, resulting in efficacy and tolerability in the control of neuropathic pain. Gabapentin-like drugs can also reduce excitability by suppressing synaptogenesis (Perret and Luo, 2009, supra; Vink and Alewood, 2012, supra, Zamponi et al., 2015, supra).

The sigma-1 (σ1) receptor was discovered 40 years ago and was initially considered a new subtype of the opioid family. This receptor is expressed both in the endoplasmic reticulum and in the plasma membrane and plays an important role in the regulation of intracellular calcium concentration. The signaling pathway associated with the activation of the σ1 receptor has not been described, although it is believed to perform an amplifying function in the activation of intracellular cascades. In this sense, the σ1 receptor regulates and modulates the activity of numerous voltage-gated ion channels, including Ca2+-, K+-, Na+, Cl-, SK and NMDA channels and the IP3 receptor.

The σ1 receptor is also known to be associated with analgesia, since σ1 receptor agonists antagonize opioid receptor-mediated analgesia, while σ1 receptor antagonists such as haloperidol potentiate it (Chien CC, Pasternak GW. Neurosci. Lett. 1995, 190, 137-9).

Much additional preclinical evidence points to a clear role for the σ1 receptor in pain (Zamanillo D, Romero L, Merlos M, Vela JM. Eur. J. Pharmacol, 2013, 716, 78-93). The creation of σ1 receptor knockout mice, which do not exhibit an obvious phenotype and discriminate sensory stimuli normally, is key in this direction. Under physiological conditions, σ1 receptor knockout mice have been found to respond indistinguishably to mechanical and thermal stimuli from WT mice, but have been shown to be more resistant to the development of pain behavior than WT mice when hypersensitivity is introduced. Consequently, in σ1-receptor knockout mice, capsaicin failed to induce mechanical hypersensitivity, both phases of formalin-induced pain were reduced, and cold and mechanical hypersensitivity were strongly attenuated after partial sciatic nerve ligation or after treatment with paclitaxel, models of neuropathic pain. Many of these effects have been confirmed using σ1-receptor antagonists and have led to the translation of one compound, S1RA, into clinical trials for the treatment of various pain conditions. The S1RA compound produced significant reductions in neuropathic pain and nerve injury anhedonia (i.e., a neuropathic pain state) and, as shown in an operant self-administration model, nerve injury mice, but not sham-operated mice, acquired operant behavior to obtain it (mainly for pain relief), demonstrating that σ1 receptor antagonism alleviates neuropathic pain and also affects some of the comorbidities (i.e., anhedonia, a major symptom in depression) associated with pain states (Romero et al. Br J Pharmacol. 2012, 166, 2289-306).

Polypharmacology is the phenomenon in which a drug binds multiple targets instead of a single target with significant affinity. The effect of polypharmacology on therapy can be positive (effective therapy) and/or negative (side effects). Positive and/or negative effects can be due to binding to the same or different subsets of targets; binding to some targets may have no effect. Multicomponent drugs or multitarget drugs can overcome the problem of toxicity and other side effects associated with high doses of single drugs by counteracting biological compensation, providing a reduced dose of each compound, or accessing environment-specific multitarget mechanisms of action. Because multitarget mechanisms of action require their targets to be accessible for coordinated action, synergy can be expected to occur over a narrower range of cellular phenotypes given the differential expression of drug targets compared to the activity parameters of individual agents. In fact, it has been experimentally demonstrated that synergistic drug combinations are generally more specific for particular cell types than the activity parameters of individual drugs, such selectivity being achieved through differential expression of drug targets in cell types associated with therapeutic, but not toxic, effects (Lehar et al., Nat. Biotechnol. 2009, 27, 659-666).

In the case of chronic pain, which is a multifactorial disease, multitargeted drugs can provide coordinated pharmacological action on multiple targets and signaling pathways that mediate pain signaling. Because they effectively take advantage of biological complexity, multitargeted (or multicomponent) drug approaches are among the most promising approaches to treating multifactorial diseases such as pain (Gilron et al., Lancet Neurol. 2013, 12, 1084–95). In fact, positive synergistic interactions of several compounds, including analgesics, have already been described (Schröder et al., J. Pharmacol. Exp Ther. 2011, 337, 312-20. Erratum in: J. Pharmacol. Exp. Ther. 2012, 342, 232; Zhang et al., Cell Death Dis. 2014, 5:e1138; Gilron et al., 2013, supra).

Given the significant differences in pharmacokinetics, metabolism, and bioavailability, recomposition of drug combinations (multiple drugs) is difficult. Furthermore, two drugs that are generally safe when dosed individually may not be considered safe in combination. In addition to the possibility of adverse drug-drug interactions, if network pharmacology theory suggests that a phenotypic effect can be mediated by multiple targets, then such combined phenotypic perturbation may be beneficial or harmful. A major obstacle to both drug combination strategies is the regulatory requirement to demonstrate that each individual drug is safe alone and in combination (Hopkins et al, Nat. Chem. Biol. 2008, 4, 682-90).

An alternative strategy for multitarget therapy is to develop a single compound with selective polypharmacology (multitarget drug). Many approved drugs have been shown to act on multiple targets. Dosing a single compound may have advantages over a combination of drugs with respect to the respective pharmacokinetics and biodistribution. Indeed, minimal drug exposures due to incompatible pharmacokinetics between the components of a combination therapy may create a window of opportunity at a low dose in which reduced selection pressure may drive drug resistance. With respect to drug approval, obtaining approval of a single compound acting on multiple targets faces significantly lower regulatory hurdles than obtaining approval of a combination of new drugs (Hopkins, 2008, supra).

As described above, the σ1 receptor, as well as the α2δ1 subunit, modulate intracellular calcium concentration and voltage-gated calcium channel activity. There is also robust clinical and preclinical data linking both targets to the treatment of chronic neuropathic pain. Thus, the present application also addresses the benefits of having bidirectional activity on the _α2δ -1 subunit of voltage-gated calcium channels and the σ1 receptor in the same molecule for the treatment of chronic pain.

Pain is multimodal in nature, as multiple mediators, signaling pathways, and molecular mechanisms are involved in virtually all pain conditions. Therefore, monomodal therapies can be complemented by dual mechanisms of action to provide comprehensive pain relief. Combining existing drugs is now common clinical practice, and many efforts are directed toward identifying the best combination of available drugs in clinical trials (Mao J, Gold MS, Backonja MJ Pain, 2011, 12, 157-166).

Accordingly, there is still a need to find compounds that have alternative or improved pharmacological activity in the treatment of pain, that are both effective and exhibit the necessary selectivity, and that have adequate "drug-ability" properties, i.e. adequate pharmaceutical properties related to administration, distribution, metabolism and excretion.

The present inventors have discovered a number of compounds that exhibit primary pharmacological activity on the α ₂ δ subunit, in particular the α ₂ δ-1 subunit of the voltage-dependent calcium channel, or compounds that exhibit bidirectional pharmacological activity on both the α ₂ δ subunit, in particular the α ₂ δ-1 subunit of the voltage-dependent calcium channel, and the σ1 receptor, resulting in an innovative, effective, complementary and alternative solution for the treatment of pain.

Taking into account the existing results of currently available drugs and clinical practices, the present invention provides a solution by combining into one compound binding to two different targets related to pain treatment. This was achieved primarily by providing compounds according to the present invention that bind to both the σ1 receptor and the α ₂ δ subunit, in particular the α ₂ δ-1 subunit, of the voltage-dependent calcium channel.

WO 2018154133 discloses [1,2,4]triazolo[1,5-a]pyrimidinyl derivatives substituted with piperidine, morpholine or piperazine as O-GlcNAc hydrolase inhibitors useful for the treatment of Alzheimer's disease, but does not mention bidirectional activity for the treatment of pain.

BRIEF DESCRIPTION OF THE INVENTION

The present invention identifies a family of structurally distinct pyrazolo[1,5-a]pyrimidine derivatives encompassed by formula (I) that have pharmacological activity at both the _α2δ subunit, in particular the _α2δ -1 subunit, of the voltage-gated calcium channel and the σ1 receptor, thereby solving the above-mentioned problem of identifying alternative or improved methods for treating pain by providing such compounds of action.

The main object of the present invention is to provide a compound having bidirectional activity, binding to the α ₂ δ subunit, in particular the α ₂ δ-1 subunit, of the voltage-dependent calcium channel and the σ1 receptor for use in the treatment of pain.

In a main aspect, the present invention is directed to a compound of general formula (I),

where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', X, m, n and t are defined below in a similar description.

Another object of the present invention relates to various processes for preparing compounds of general formula (I).

Another additional object of the present invention relates to the use of intermediates for the preparation of compounds of general formula (I).

Another object of the present invention is a pharmaceutical composition containing a compound of formula (I).

Finally, the object of the present invention is the use of the compound as a medicine and more particularly for the treatment of pain and pain-related conditions.

DETAILED DESCRIPTION OF THE INVENTION

The present invention is directed to a family of structurally diverse pyrazolo[1,5-a]pyrimidine derivatives that exhibit bidirectional pharmacological activity against both the α ₂ δ subunit, in particular the α ₂ δ-1 subunit, of the voltage-gated calcium channel, and the σ ₁ receptor.

The present invention is directed to compounds having bidirectional activity, binding to the α ₂ δ subunit, in particular the α ₂ δ-1 subunit, of the voltage-dependent calcium channel and the σ ₁ receptor for use in the treatment of pain and related disorders.

Since the present invention is directed to providing a compound or a chemically related series of compounds that function as dual acting ligands for the _α2δ subunit, in particular the _α2δ -1 subunit, the voltage-gated calcium channel and the _σ1 receptor, a preferred embodiment is one in which the compound is characterized by binding to the receptor, expressed as K _i , according to the following scales:

K _i (σ ₁ ) is preferably <1000 nM, more preferably <500 nM, even more preferably <100 nM.

K _i (α ₂ δ-1) is preferably <10000 nM, more preferably <5000 nM, even more preferably <500 nM, or even more preferably <100 nM.

Preferably, if K _i (σ ₁ ) >1000 nM, the following scale was chosen to represent binding to the σ1 receptor:

+ K _i (σ ₁ ) >1000 nM or inhibition ranges from 1% to 50%.

Preferably, if K _i (α ₂ δ-1) >5000 nM, the following scale was chosen to represent the binding of the α ₂ δ-1 subunit of voltage-gated calcium channels:

+ K _i (α ₂ δ-1) >5000 nM or inhibition ranges from 1% to 50%.

The Applicant has unexpectedly discovered that the problem of providing a new effective and alternative solution for the treatment of pain and pain-related disorders can be solved by using an analgesic approach that combines two types of activity in a single drug (i.e. dual-acting ligands that are bifunctional and bind to the σ1 receptor and to the _α2δ subunit, in particular the _α2δ -1 subunit, of the voltage-gated calcium channel).

As described above, the σ1 receptor as well as the α ₂ δ1 subunit modulate intracellular calcium concentration and voltage-dependent calcium channel activity. There is also robust clinical and preclinical evidence linking both targets to the treatment of chronic neuropathic pain. Thus, the present invention also relates to the advantages of having bidirectional activity on the α ₂ δ-1 subunit of voltage-dependent calcium channels and the σ1 receptor in the same molecule for the treatment of pain, i.e. binding to two different targets associated with the treatment of pain.

A dual-acting compound, which is characterized by binding to both the σ ₁ receptor and the α ₂ δ subunit of the voltage-dependent calcium channel, demonstrates extremely significant therapeutic potential by achieving exceptional analgesia.

An additional benefit of using multiple engineered ligands is a low risk of drug-drug interactions compared to drug mixtures or multicomponent drugs, thereby providing simpler pharmacokinetics and less interpatient variability. In addition, this approach may improve patient compliance and expand the therapeutic applicability of single-mode drugs by addressing more complex etiologies.

However, it should be noted that the functions "antagonism" and "agonism" are also subdivided due to their effect into subfunctions such as partial agonism or inverse agonism. Accordingly, the functional groups of compounds should be considered within a relatively wide range.

An antagonist blocks or attenuates agonist-mediated responses. Known functional subgroups are neutral antagonists or inverse agonists.

An agonist increases the activity of a receptor above its baseline level. The known functional subgroups are full agonists or partial agonists.

In its broader aspect, the present invention is directed to compounds of general formula (I),

Where

m is equal to 1, 2, 3, or 4;

n is equal to 1 or 2;

t is equal to 0 or 1;

X is selected from the group consisting of the bond, -[CH ₂ ] _p -, -[CH ₂ ] _p NR _x [CH ₂ ] _q -, -[CH ₂ ] _p O[CH ₂ ] _q -, -[CH ₂ ] _p NR _x C(O)[CH ₂ ] _q - and -[CH ₂ ] _p NR _x CH(CH ₃ )-;

Where

p is 0, 1, 2, 3, or 4;

q is equal to 0, 1, 2, 3, or 4;

R _x is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₁ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy, -OR ₆ , -NR ₆ R ₆ ', -CN, cycloalkyl, aryl and heterocyclyl;

R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, haloalkyl, haloalkoxy; substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylheterocyclyl;

R ₆ ' is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₆ and R ₆ ' taken together with the nitrogen atom to which they are attached form a substituted or unsubstituted heterocyclyl;

R ₂ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, halogen, haloalkyl, haloalkoxy and -OR ₇ ;

R ₇ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₃ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy and -OR ₈ ;

R ₈ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl;

R ₅ and R ₅ ' are independently selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, haloalkyl and haloalkoxy.

Such compounds according to the present invention are optionally present in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or their corresponding salt or their corresponding solvate.

In another embodiment, such compounds according to the present invention are optionally present in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate, or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or a corresponding salt thereof.

Note that "or their corresponding salt" also means "or their corresponding pharmaceutically acceptable salt". This applies to all below-described embodiments and uses of "salt", which is thus equivalent to "pharmaceutically acceptable salt".

In a specific embodiment, the following connection is excluded:

In a specific embodiment, the heterocyclyl in R ₄ is not a thiazole.

In a particular embodiment, the heterocyclyl in R ₄ is a heterocyclyl that does not contain a sulfur atom.

In a particular embodiment, the heterocyclyl in R ₄ is a monocyclic heterocyclyl that does not contain a sulfur atom.

In a particular embodiment, the heterocyclyl in R ₄ is a monocyclic heterocyclyl selected from the group consisting of oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, isothiazole, tetrahydropyran, tetrahydrofuran, morpholine, thiomorpholine, furan, triazole, isoxazole, pyrazole, thiophene, pyrrole, pyrazine, oxopyrrolidine and pyrimidine.

In a particular embodiment, R ₁ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy, -OR ₆ , -NR ₆ R ₆ ', -CN, cycloalkyl, aryl, and heterocyclyl.

In a particular embodiment, R ₂ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkyl cycloalkyl, halogen, haloalkyl, haloalkoxy, and -OR ₇ ;

In a further embodiment, the compound according to the present invention is a compound of general formula (I),

Where

m is equal to 1, 2, 3, or 4;

n is equal to 1 or 2;

t is equal to 0 or 1;

X is selected from the group consisting of the bond, -[CH ₂ ] _p -, -[CH ₂ ] _p NR _x [CH ₂ ] _q -, -[CH ₂ ] _p O[CH ₂ ] _q -, -[CH ₂ ] _p NR _x C(O)[CH ₂ ] _q - and -[CH ₂ ] _p NR _x CH(CH ₃ )-;

Where

p is 0, 1, 2, 3, or 4;

q is equal to 0, 1, 2, 3, or 4;

R _x is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

wherein alkyl, alkenyl or alkynyl in R _X , when substituted, is substituted by one or more substituents selected from halogen, -CN, haloalkyl and haloalkoxy;

R ₁ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy, -OR ₆ , -NR ₆ R ₆ ', -CN, cycloalkyl, aryl and heterocyclyl;

R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, haloalkyl, haloalkoxy; substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylheterocyclyl;

R ₆ ' is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

alternatively, R ₆ and R ₆ ' taken together with the nitrogen atom to which they are attached form a substituted or unsubstituted heterocyclyl;

wherein alkyl, alkenyl or alkynyl in R ₁ when substituted is substituted by one or more substituents selected from -OR ₁₁ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₁ R ₁₁ ';

wherein said cycloalkyl, aryl or heterocyclyl in R ₁ , when substituted, are substituted by one or more substituents selected from halogen, -R ₁₁ , -[CH ₂ ] _r OR ₁₁ , =O, -NO ₂ , -[CH ₂ ] _r NR ₁₁ R ₁₁ ', -NR ₁₁ C(O)R ₁₁ ', -NR ₁₁ S(O) ₂ R ₁₁ ', -S(O) ₂ NR ₁₁ R ₁₁ ', -NR ₁₁ C(O)NR ₁₁ 'R ₁₁ '', -SR ₁₁ , -S(O)R ₁₁ , -S(O) ₂ R ₁₁ , -CN, haloalkyl, haloalkoxy, -C(O)R ₁₁ , -C(O)OR ₁₁ , -C(O)NR ₁₁ R ₁₁ ', -OCH ₂ CH ₂ OR ₁₁ , -NR ₁₁ S(O) ₂ NR ₁₁ 'R ₁₁ '' and -C(CH ₃ ) ₂ OR ₁₁ ;

wherein R ₁₁ , R ₁₁ ' and R ₁₁ '' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;

R ₂ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, halogen, haloalkyl, haloalkoxy and -OR ₇ ;

R ₇ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

wherein alkyl, alkenyl or alkynyl in R ₂ when substituted is substituted by one or more substituents selected from -OR ₂₁ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₂₁ R ₂₁ ';

wherein said cycloalkyl in R ₂ , also in alkylcycloalkyl, in case of substitution is substituted by one or more substituents selected from halogen, -R ₂₁ , -[CH ₂ ] _r OR ₂₁ , =O, -NO ₂ , -[CH ₂ ] _r NR ₂₁ R ₂₁ ', -NR ₂₁ C(O)R ₂₁ ', -NR ₂₁ S(O) ₂ R ₂₁ ', -S(O) ₂ NR ₂₁ R ₂₁ ', -NR ₂₁ C(O)NR ₂₁ 'R ₂₁ '', -SR ₂₁ , -S(O)R ₂₁ , -S(O) ₂ R ₂₁ , -CN, haloalkyl, haloalkoxy, -C(O)R ₂₁ , -C(O)OR ₂₁ , -C(O)NR ₂₁ R ₂₁ ', -OCH ₂ CH ₂ OR ₂₁ , -NR ₂₁ S(O) ₂ NR ₂₁ 'R ₂₁ '' and -C(CH ₃ ) ₂ OR ₂₁ ;

wherein R ₂₁ and R ₂₁ ' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₃ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy and -OR ₈ ;

R ₈ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

wherein alkyl, alkenyl or alkynyl in R ₃ when substituted is substituted by one or more substituents selected from OR ₃₁ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₃₁ R ₃₁ ';

wherein R ₃₁ and R ₃₁ ' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl;

wherein alkyl, alkenyl or alkynyl in R ₄ , when substituted, is substituted by one or more substituents selected from -OR ₄₁ , halogen, -CN, haloalkyl, haloalkoxy, -NR ₄₁ R ₄₁ ';

wherein said cycloalkyl, aryl or heterocyclyl in R4, when substituted, is substituted by one or more substituents selected from halogen, -R ₄₁ , -[CH ₂ ] _r OR ₄₁ , =O, -NO ₂ , -[CH ₂ ] _r NR ₄₁ R ₄₁ ', -NR ₄₁ C(O)R ₄₁ ', -NR ₄₁ S(O) ₂ R ₄₁ ', -S(O) ₂ NR ₄₁ R ₄₁ ', -NR ₄₁ C(O)NR ₄₁ 'R ₄₁ '', -SR ₄₁ , -S(O)R ₄₁ , -S(O) ₂ R ₄₁ , -CN, haloalkyl, haloalkoxy, -C(O)R ₄₁ , -C(O)OR ₄₁ , -C(O)NR ₄₁ R ₄₁ ', -OCH ₂ CH ₂ OR ₄₁ , -NR ₄₁ S(O) ₂ NR ₄₁ 'R ₄₁ '' and -C(CH ₃ ) ₂ OR ₄₁ ;

wherein _R41 , _R41 ' and _R41 '' are independently selected from hydrogen, substituted or unsubstituted _C1-6 alkyl, substituted or unsubstituted _C2-6 alkenyl and substituted or unsubstituted _C2-6 alkynyl; _R5 and _R5 ' are independently selected from the group consisting of hydrogen, substituted or unsubstituted _C1-6 alkyl, substituted or unsubstituted _C2-6 alkenyl, substituted or unsubstituted _C2-6 alkynyl, haloalkyl and haloalkoxy;

wherein alkyl, alkenyl or alkynyl in R ₅ and R ₅ ', when substituted, are substituted by one or more substituents selected from -OR ₅₁ , halogen, -CN, haloalkyl, haloalkoxy, -NR ₅₁ R ₅₁ ';

wherein R ₅₁ and R ₅₁ ' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

alkyl, alkenyl or alkynyl, if substituted and not otherwise defined, are substituted with one or more substituents selected from -OR ₁₃ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₃ R ₁₃ ';

where R ₁₃ and R ₁₃ ' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, and unsubstituted C _2-6 alkynyl;

aryl, heterocyclyl or cycloalkyl, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted and not otherwise defined, are substituted by one or more substituents selected from halogen, -R ₁₄ , -[CH ₂ ] _r OR ₁₄ , =O, -NO ₂ , -[CH ₂ ] _r NR ₁₄ R ₁₄ ', -NR ₁₄ C(O)R ₁₄ ', -NR ₁₄ S(O) ₂ R ₁₄ ', -S(O) ₂ NR ₁₄ R ₁₄ ', -NR ₁₄ C(O)NR ₁₄ 'R ₁₄ '', -SR ₁₄ , -S(O)R ₁₄ , S(O) ₂ R ₁₄ , -CN, haloalkyl, haloalkoxy, -C(O)R ₁₄ , -C(O)OR ₁₄ , -C(O)NR ₁₄ R ₁₄ ', -OCH ₂ CH ₂ OR ₁₄ , -NR ₁₄ S(O) ₂ NR ₁₄ 'R ₁₄ '' and -C(CH ₃ ) ₂ OR ₁₄ ;

wherein R ₁₄ , R ₁₄ ' and R ₁₄ '' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; wherein r is 0, 1, 2 or 3;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound of general formula (I),

where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', X and m are defined below in the detailed description;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound of general formula (I ² '),

where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R _x , m, n, t, p and q are defined below in the detailed description;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound of general formula (I ² '),

where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R _x , m, n, p and q are defined below in the detailed description;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound of general formula (I ³ '),

where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R ₆ , R ₆ ', m, n, t and p are defined below in the detailed description;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound of general formula (I ³ '),

where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R ₆ , R ₆ ', m, n, and p are defined below in the detailed description;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

For clarification purposes: all groups and definitions described in this description and referring to compounds of general formula (I) also apply to compounds of general Markush formula (I'), (I ² '), (I ^2a '), (I ³ ') or (I ^3a ') (where applicable) and to all intermediates of the synthesis, if these groups are present in the said general Markush formula, since compounds of general Markush formula (I'), (I ² '), (I ^2a '), (I ³ ') or (I ^3a ') are included within the scope of the broader definition of general Markush formula (I).

For clarification purposes: the expression, for example, "the ring in _R8 - _R8 '" means the ring formed when _R8 and _R8 ' form a ring together with the atom(s) to which they are attached. This ring may then be substituted or unsubstituted. This definition is also generally applicable and may also be used as a definition of any other ring (preferably cycloalkyls, heterocyclyls or aryls) formed from two different functional groups, such as "the ring in _Ri - _Ri' " means the ring formed when _Ri and _Ri ' form a ring together with the atom(s) to which they are attached. This ring may then be substituted or unsubstituted.

In the context of the present invention, "alkyl" should be understood to mean saturated, linear or branched hydrocarbons, which may be unsubstituted or substituted one or more times. It covers, for example, -CH ₃ and -CH ₂ -CH ₃ . In these radicals, C _1-2 -alkyl is C1- or C2-alkyl, C _1-3 -alkyl is C1-, C2- or C3-alkyl, C _1-4 -alkyl is C1-, C2-, C3- or C4-alkyl, C _1-5 -alkyl is C1-, C2-, C3-, C4- or C5-alkyl, C _1-6 -alkyl is C1-, C2-, C3-, C4-, C5- or C6-alkyl, C _1-7 -alkyl is C1-, C2-, C3-, C4-, C5-, C6- or C7-alkyl, C _1-8 -alkyl is C1-, C2-, C3-, C4-, C5-, C6-, C7- or C8-alkyl, C _1-10 -alkyl is C1-, C2-, C3-, C4-, C5-, C6-, C7-, C8-, C9- or C10-alkyl and C _1-18 -alkyl are C1-, C2-, C3-, C4-, C5-, C6-, C7-, C8-, C9-, C10-, C11-, C12-, C13-, C14-, C15-, C16-, C17- or C18-alkyl. The alkyl radicals are preferably methyl, ethyl, propyl, methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl, 2,2-dimethylpropyl, hexyl, 1-methylpentyl if also substituted by CHF ₂ , CF ₃ or CH ₂ OH, etc. Preferably, "alkyl" is to be understood in the context of the present invention as C _1-8 alkyl, such as methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl or octyl; preferably, "alkyl" is C _1-6 alkyl, such as methyl, ethyl, propyl, butyl, pentyl or hexyl; more preferably, it is C _1-4 alkyl, such as methyl, ethyl, propyl or butyl.

"Alkenyl" is to be understood as meaning unsaturated, linear or branched hydrocarbons which may be unsubstituted or substituted one or more times. It embraces groups such as, for example, -CH=CH- _CH3 . The alkenyl radicals are preferably vinyl (ethenyl), allyl (2-propenyl). Preferably, in the context of the present invention, alkenyl is _C2-10 alkenyl or _C2-8 alkenyl, such as ethylene, propylene, butylene, pentylene, hexylene, heptylene or octylene; or is _C2-6 alkenyl, such as ethylene, propylene, butylene, pentylene or hexylene; or is _C2-4 alkenyl, such as ethylene, propylene or butylene.

"Alkynyl" is to be understood as meaning unsaturated, linear or branched hydrocarbons which may be unsubstituted or substituted one or more times. It embraces groups such as, for example, -C=C- _CH3 (1-propynyl). Preferably, alkynyl in the context of the present invention is _C2-10 -alkynyl or _C2-8 -alkynyl, such as ethyne, propyne, butyne, pentyne, hexyne, heptyne or octyne; or is _C2-6 -alkynyl, such as ethyne, propyne, butyne, pentyne or hexyne; or is _C2-4 -alkynyl, such as ethyne, propyne, butyne, pentyne or hexyne.

With respect to alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl), alkenyl, alkynyl and O-alkyl, unless otherwise specified, the term "substituted" in the context of the present invention should be understood as meaning the replacement of at least one radical representing hydrogen on a carbon atom by halogen (F, Cl, Br, I), -NR _k R _k ', -SR _k , -S(O)R _k , -S(O) ₂ R _k , -OR _k , -C(O)R _k , -C(O)OR _k , -CN, -C(O)NR _k R _k ', haloalkyl, haloalkoxy, wherein R _k is R ₁₁ , R ₁₃ , R ₂₁ , R ₃₁ , R ₄₁ or R ₅₁ (wherein R _k ' is R ₁₁ ', R ₁₃ ', R ₂₁ ', R ₃₁ ', R ₄₁ ' or R ₅₁ '); where R ₁ - R ₅₁ ' are defined in the description, and if different radicals R ₁ - R ₅₁ ' or if m, n, t or r are present simultaneously in formula I, they may be identical or different.

Most preferably, with respect to alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl), alkenyl, alkynyl or O-alkyl, the term "substituted" is to be understood in the context of the present invention as any alkyl (also in alkylaryl, alkylheterocyclyl or alkylcycloalkyl), alkenyl, alkynyl or O-alkyl which is substituted by one or more halogen atoms (F, Cl, Br, I), -NR _k R _k ', -OR _k , -CN, -SR _k , haloalkyl, haloalkoxy, wherein R _k is R ₁₁ , R ₁₃ , R ₂₁ , R ₃₁ , R ₄₁ or R ₅₁ (wherein R _k ' is R ₁₁ ', R ₁₃ ', R ₂₁ ', R ₃₁ ', R ₄₁ ' or R ₅₁ '); where R ₁ - R ₅₁ ' are defined in the description, and if different radicals R ₁ - R ₅₁ ' or if m, n, t or r are present simultaneously in formula I, then they may be identical or different.

More than one substitution is possible on the same molecule, and also at the same carbon atom with the same or different substituents. This includes, for example, 3 hydrogen atoms substituted at the same C atom, as in the case of CF ₃ , or at different positions of the same molecule, as in the case of, for example, -CH(OH)-CH=CH-CHCl ₂ .

In the context of the present invention, "haloalkyl" is to be understood as meaning alkyl substituted one or more times by halogen (selected from F, Cl, Br, I). It covers, for example, _-CH2Cl , _-CH2F , _-CHCl2 , _-CHF2 , _-CCl3 , _-CF3 and -CH2 _{- CHCI2} . Preferably, "haloalkyl" is to be understood in the context of the present invention as halogen-substituted _C1-4 alkyl, which is halogen-substituted C1-, C2-, C3- or C4-alkyl. Thus, halogen-substituted alkyl radicals are preferably methyl, ethyl, propyl and butyl. Preferred examples include _-CH2Cl , _-CH2F , _-CHCl2 , _-CHF2 and _-CF3 .

In the context of the present invention, "haloalkoxy" is to be understood as meaning -O-alkyl substituted one or more times by halogen (selected from F, Cl, Br, I). It comprises, for example, _-OCH2Cl , _-OCH2F , _-OCHCl2 , _-OCHF2 , _-OCCl3 , _-OCF3 and -OCH2 _{- CHCI2} . Preferably, haloalkyl is to be understood in the context of the present invention as halogen-substituted _-OC1-4 -alkyl, which is halogen-substituted C1-, C2-, C3- or C4-alkoxy. Thus, halogen-substituted alkyl radicals are preferably O-methyl, O-ethyl, O-propyl and O-butyl. Preferred examples include -OCH ₂ Cl, -OCH ₂ F, -OCHCl ₂ , -OCHF ₂ and -OCF ₃ .

In the context of the present invention, "cycloalkyl" should be understood to mean saturated and unsaturated (but not aromatic) cyclic hydrocarbons (without a heteroatom in the ring), which may be unsubstituted or substituted one or more times. Moreover, C _3-4 -cycloalkyl is C3- or C4-cycloalkyl, C _3-5 -cycloalkyl is C3-, C4- or C5-cycloalkyl, C _3-6 cycloalkyl is C3-, C4-, C5- or C6-cycloalkyl, C _3-7 -cycloalkyl is C3-, C4-, C5-, C6- or C7-cycloalkyl, C _3-8 -cycloalkyl is C3-, C4-, C5-, C6-, C7- or C8-cycloalkyl, C _4-5 -cycloalkyl is C4- or C5-cycloalkyl, C _4-6 -cycloalkyl is C4-, C5- or C6-cycloalkyl, C _4-7 -cycloalkyl is C4-, C5-, C6- or C7-cycloalkyl, C _5-6 -cycloalkyl is C5- or C6-cycloalkyl and _C5-7 -cycloalkyl is C5-, C6- or C7-cycloalkyl. Examples are cyclopropyl, 2-methylcyclopropyl, cyclopropylmethyl, cyclobutyl, cyclopentyl, cyclopentylmethyl, cyclohexyl, cycloheptyl, cyclooctyl and also adamantyl. Preferably, in the context of the present invention, cycloalkyl is _C3-8 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; or is _C3-7 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; or is _C3-6 cycloalkyl, such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl, in particular cyclopentyl or cyclohexyl.

Aryl is to be understood as meaning 5-18-membered mono- or polycyclic ring systems with at least one aromatic ring, but without heteroatoms even exclusively in one of the rings. Examples are phenyl, naphthyl, fluoranthenyl, fluorenyl, tetralinyl or indanyl, 9H-fluorenyl or anthracenyl radicals, which may be unsubstituted or substituted one or more times. Most preferably, "aryl" is to be understood in the context of the present invention as phenyl, naphthyl or anthracenyl, preferably "aryl" is phenyl.

A heterocyclyl radical or group (also referred to as heterocyclyl hereinafter) should be understood to mean 5-18-membered mono- or polycyclic heterocyclic ring systems with at least one saturated or unsaturated ring that contains one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur in the ring. The heterocyclic group may also be substituted one or more times.

Subgroups within heterocyclyls as understood herein include heteroaryls and non-aromatic heterocyclyls:

- heteroaryl (equivalent to heteroaromatic radicals or aromatic heterocyclyls) is an aromatic 5-18-membered mono- or polycyclic heterocyclic ring system with one or more rings, of which at least one aromatic ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur; preferably represents a 5-18-membered mono- or polycyclic aromatic heterocyclic ring system with one or two rings, of which at least one aromatic ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur, more preferably selected from furan, benzofuran, thiophene, benzothiophene, pyrrole, pyridine, pyrimidine, pyrazine, quinoline, isoquinoline, phthalazine, benzothiazole, indole, benzotriazole, carbazole, quinazoline, thiazole, imidazole, pyrazole, oxazole, thiophene and benzimidazole;

- non-aromatic heterocyclyl is a 5-18-membered mono- or polycyclic heterocyclic ring system with one or more rings, of which at least one ring, wherein this (or these) ring(s) is (are not) in this case aromatic (aromatic), contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur; preferably represents a 5-18-membered mono- or polycyclic heterocyclic ring system with one or two rings, of which one or both rings, wherein these one or two rings are not aromatic in this case, contains/contain one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur, more preferably selected from oxazepane, pyrrolidine, piperidine, piperazine, tetrahydropyran, morpholine, indoline, oxopyrrolidine, benzodioxane, in particular benzodioxane, morpholine, tetrahydropyran, piperidine, oxopyrrolidine and pyrrolidine. Preferably, in the context of the present invention, heterocyclyl is defined as a 5- to 18-membered mono- or polycyclic heterocyclic ring system with one or more saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur. Preferably, it is a 5- to 18-membered mono- or polycyclic heterocyclic ring system with one or two saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur.

Preferred examples of heterocyclyls include oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, pyridine, pyrimidine, piperidine, piperazine, benzofuran, benzimidazole, indazole, benzodiazole, thiazole, benzothiazole, tetrahydropyran, morpholine, indoline, furan, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, isoquinoline, tetrahydroisoquinoline, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole, oxopyrrolidine, pyrimidine, benzodioxolane, benzodioxane, carbazole and quinazoline, especially pyridine, pyrazine, indazole, benzodioxane, thiazole, benzothiazole, morpholine, tetrahydropyran, pyrazole, imidazole, piperidine, thiophene, indole, benzimidazole, pyrrolo[2,3b]pyridine, benzoxazole, oxopyrrolidine, pyrimidine, oxazepane, azetidine and pyrrolidine.

In the context of the present invention, oxopyrrolidine should be understood to mean pyrrolidin-2-one.

N-containing heterocyclyl is a heterocyclic ring system with one or more saturated or unsaturated rings, of which at least one ring contains nitrogen and optionally one or more additional heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur; preferably is a heterocyclic ring system with one or two saturated or unsaturated rings, of which at least one ring contains nitrogen and optionally one or more additional heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur; more preferably selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, benzimidazole, indazole, benzothiazole, benzodiazole, morpholine, indoline, triazole, isoxazole, pyrazole, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydrothienopyridine, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazoloxopyrrolidine, carbazole or thiazole.

In the context of the present invention, a cyclic amide is defined as a subgroup of heterocyclyl (as defined above) formed by cyclization of a carbon sequence containing at least the sequence

, forming part of a ring. Said cyclic amide may optionally be condensed with the ring system. Preferably, the cyclic amide is "indolin-2-one". The cyclic amide may be substituted or unsubstituted as defined for heterocyclyl above.

In the context of the present invention, a cyclic urea is defined as a subgroup of heterocyclyl (as defined above) formed by cyclization of a carbon sequence, containing at least the sequence

, forming part of a ring. Said cyclic urea may optionally be condensed with the ring system. Preferably, the cyclic urea is "1H-benzo[d]imidazol-2(3H)-one". The cyclic urea may be substituted or unsubstituted as defined for heterocyclyl above.

With respect to aromatic heterocyclyls (heteroaryls), nonaromatic heterocyclyls, aryls and cycloalkyls, when the ring system is simultaneously within two or more of the above ring definitions, the ring system is defined first as an aromatic heterocyclyl (heteroaryl) if at least one aromatic ring contains a heteroatom. If no aromatic ring containing a heteroatom is present, the ring system is defined as a nonaromatic heterocyclyl if at least one nonaromatic ring contains a heteroatom. If no nonaromatic ring containing a heteroatom is present, the ring system is defined as an aryl if it contains at least one aryl ring. If no aryl is present, the ring system is defined as a cycloalkyl if at least one nonaromatic cyclic hydrocarbon is present.

In the context of the present invention, alkylaryl is understood to mean an aryl group (see above) bonded to another atom via a C _1-6 -alkyl (see above), which may be branched or linear and unsubstituted or substituted one or more times. Preferably, alkylaryl is understood to mean an aryl group (see above) bonded to another atom via 1 to 4 groups (-CH ₂ -). Most preferably, alkylaryl is benzyl (i.e. -CH ₂ -phenyl). More preferably, the "alkyl" in alkylaryl is unsubstituted alkyl.

In the context of the present invention, alkylheterocyclyl is understood to mean a heterocyclyl group bonded to another atom via a C _1-6 -alkyl (see above), which may be branched or linear and unsubstituted or substituted one or more times. Preferably, alkylheterocyclyl is understood to mean a heterocyclyl group (see above) bonded to another atom via 1-4 groups (-CH ₂ -). Most preferably, alkylheterocyclyl is -CH ₂ -pyridine. More preferably, the "alkyl" in alkylheterocyclyl is unsubstituted alkyl.

In the context of the present invention, alkylcycloalkyl is understood to mean a cycloalkyl group bonded to another atom via a C _1-6 -alkyl (see above), which may be branched or linear and unsubstituted or substituted one or more times. Preferably, alkylcycloalkyl is understood to mean a cycloalkyl group (see above) bonded to another atom via 1 to 4 groups (-CH ₂ -). Most preferably, alkylcycloalkyl is -CH ₂ -cyclopropyl. More preferably, the "alkyl" in alkylcycloalkyl is unsubstituted alkyl.

Preferably, the aryl is a monocyclic aryl. More preferably, the aryl is a 5-, 6-, or 7-membered monocyclic aryl. Even more preferably, the aryl is a 5- or 6-membered monocyclic aryl.

Preferably, the heteroaryl is a monocyclic heteroaryl. More preferably, the heteroaryl is a 5-, 6-, or 7-membered monocyclic heteroaryl. Even more preferably, the heteroaryl is a 5- or 6-membered monocyclic heteroaryl.

Preferably, the non-aromatic heterocyclyl is a monocyclic non-aromatic heterocyclyl. More preferably, the non-aromatic heterocyclyl is a 4-, 5-, 6- or 7-membered monocyclic non-aromatic heterocyclyl. Even more preferably, the non-aromatic heterocyclyl is a 5- or 6-membered monocyclic non-aromatic heterocyclyl.

Preferably, the cycloalkyl is a monocyclic cycloalkyl. More preferably, the cycloalkyl is a 3-, 4-, 5-, 6-, 7-, or 8-membered monocyclic cycloalkyl. Even more preferably, the cycloalkyl is either a 3-, 4-, 5-, or 6-membered monocyclic cycloalkyl.

Heterocyclyl is a ring system with one or more saturated and/or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur; preferably is a ring system with one saturated and/or unsaturated ring containing one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur, or a ring system with two saturated and/or unsaturated rings of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur, more preferably is selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, furan, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, isothiazole, tetrahydropyran, tetrahydrofuran, morpholine, thiomorpholine, indoline, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydroisoquinoline, tetrahydrothienopyridine, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, benzodioxolane, benzodioxane, carbazole, octahydro-ethanopyrrolopyridine, oxaspirodecane, oxadiazaspiroundecane, indolin-2-one, and quinazoline.

In general, such a heterocyclyl may contain from 3 to 32 ring atoms (preferably from 4 to 20 ring atoms or most preferably from 5 to 18 ring atoms). Thus, a heterocyclyl may contain from 3 to 12 ring atoms (preferably from 4 to 10 ring atoms, or from 5 to 8 ring atoms, or from 5 to 6 ring atoms) in the case of a heterocyclyl with one ring. Such a heterocyclyl may also contain from 5 to 22 atoms in both rings together (preferably from 6 to 16 atoms in both rings together, or from 7 to 12 atoms in both rings together, or from 8 to 10 atoms in both rings together) in the case of a heterocyclyl with two rings. Such a heterocyclyl may also contain from 7 to 32 atoms in 3 rings together (preferably from 10 to 22 atoms in three rings together, or from 12 to 20 atoms in three rings together, or from 10 to 18 atoms in three rings together) in the case of a heterocyclyl with three rings. Each ring in the ring system may independently be saturated or unsaturated.

For clarification purposes: the general Markush formula (I) is equivalent to (IZ),

where only -C(R ₅ R ₅ ')- is included in brackets, and m denotes the number of repetitions of -C(R ₅ R ₅ ')-. The same applies, where applicable, to the general Markush formulas (I), (I'), (I ² '), (I ^2a '), (I ³ ') or (I ^3a ') and to all intermediates of the synthesis.

Furthermore and for clarification purposes: it should also be understood that, naturally, if t is 0, the pyrazolopyrimidine core and the piperidine ring are still present, when applicable, in the general Markush formulas (I), (I'), (I ² '), (I ^2a '), (I ³ ') or (I ^3a '), as well as in all intermediates of the synthesis.

For clarification purposes: reference is made to the following statements below in the definitions of substitution variants of alkyl etc. or aryl etc. that "if different radicals R ₁ to R ₅₁ ' or if m, n, t or r are present simultaneously in formula I, they may be identical or different". This statement is reflected in the general formula (I ^d ) below, which is derived from general formula (I),

where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', X, m, n and t are defined in the description. In addition, R ₅ '' and R5''' are added. As stated above, this statement is thus reflected in that R5'' and R5''' are different or may be different from R ₅ and R ₅ ' or not.

The same applies mutatis mutandis to general formulas such as general formula (I) as well as to other general formulas (I'), (I ² '), (I ^2a '), (I ³ ') or (I ^3a ') and to all intermediates of the synthesis.

With respect to aryl (including alkyl-aryl), cycloalkyl (including alkyl-cycloalkyl) or heterocyclyl (including alkyl-heterocyclyl), "substituted" shall be understood, unless otherwise specified, to mean substitution of the aryl or alkyl-aryl, cycloalkyl or alkyl-cycloalkyl ring system; heterocyclyl or alkyl-heterocyclyl with one or more of halogen atoms (F, Cl, Br, I), -R _k , -OR _k , -[CH ₂ ] _r OR _k , -CN, -NO ₂ , -NR _k R _k' , -[CH ₂ ] _r NR _k R _k ', -C(O)OR _k , -C(O)R _k , -NR _k C(O)R _k' , -C(O)NR _k R _k' , -NR _k S(O) ₂ R _k' , =O, -OCH ₂ CH ₂ OH, -NR _k C(O)NR _k' R _k'' , -S(O) ₂ NR _k R _k' , -NR _k S(O) ₂ NR _k' R _k'' , haloalkyl, haloalkoxy, -SR _k , -S(O)R _k , -S(O) ₂ R _k , or -C( _CH3 ) _ORk , or substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkyl heterocyclyl, wherein _Rk , Rk _' and Rk _'' are independently either H or saturated or unsaturated, linear or branched, substituted or unsubstituted _C1-6alkyl ; saturated or unsaturated, linear or branched, substituted or unsubstituted _C1-6alkyl ; saturated or unsaturated, linear or branched, substituted or unsubstituted _-OC1-6alkyl (alkoxy); saturated or unsaturated, linear or branched, substituted or unsubstituted _SC1-6alkyl ; saturated or unsaturated, linear or branched, substituted or unsubstituted -C(O)-C _1-6 -alkyl group; saturated or unsaturated, linear or branched, substituted or unsubstituted -C(O)-O-C _1-6 -alkyl group; substituted or unsubstituted aryl or alkyl-aryl; substituted or unsubstituted cycloalkyl or alkyl-cycloalkyl; substituted or unsubstituted heterocyclyl or alkyl-heterocyclyl, wherein R _k is one of R ₁₁ , R ₁₄ , R ₂₁ or R ₄₁ (wherein R _k ' is one of R ₁₁ ', R ₁₄ ', R ₂₁ ' or R ₄₁ ', wherein R _k '' is one of R ₁₁ '', R ₁₄ '', R ₂₁ '' or R ₄₁ ''); wherein R ₁ - R ₅₁ ' are defined in the description, and wherein if different radicals R ₁ - R ₅₁ ' or if m, n, t or r are present simultaneously in formula I, they may be identical or different.

Most preferably, with respect to aryl (including alkyl-aryl), cycloalkyl (including alkyl-cycloalkyl) or heterocyclyl (including alkyl-heterocyclyl), "substituted" should be understood in the context of the present invention such that any aryl, cycloalkyl and heterocyclyl that is substituted is substituted (also in alkylaryl, alkylcycloalkyl or alkylheterocyclyl) by one or more of halogen atoms (F, Cl, Br, I), -R _k , -OR _k , -[CH ₂ ] _r OR _k , -CN, -NO ₂ , -NR _k R _k''' , -[CH ₂ ] _r NR _k R _k ', -C(O)R _k , NR _k C(O)R _k' , -NR _k S(O) ₂ R _k' , =O, -S(O) ₂ NR _k R _k' , -NR _k C(O)NR _k' R _k'' , haloalkyl, haloalkoxy, -SR _k , -S(O)R _k , or -S(O) ₂ R _k , or substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, substituted or unsubstituted alkylheterocyclyl, wherein R _k is one of R ₁₁ , R ₁₄ , R ₂₁ or R ₄₁ (wherein R _k' is one of R ₁₁ ', R ₁₄ ', R ₂₁ ' or R ₄₁ '; wherein R _k'' is one of R ₁₁ '', R ₁₄ '', R ₂₁ '' or R ₄₁ ''); where R ₁ - R ₅₁ ' are defined in the description, and wherein if different radicals R ₁ - R ₅₁ ' or if m, n, t or r are present simultaneously in formula I, they may be identical or different.

With respect to cycloalkyl (including alkyl-cycloalkyl) or heterocyclyl (including alkylheterocyclyl), namely non-aromatic heterocyclyl (including non-aromatic alkyl-heterocyclyl), "substituted" shall also be understood, unless otherwise specified, to mean substitution of the ring system of the cycloalkyl or alkyl-cycloalkyl, non-aromatic heterocyclyl or non-aromatic alkyl-heterocyclyl by (resulting in the formation of a spiro structure) and/or using =O.

Moreover, with respect to cycloalkyl (including alkyl-cycloalkyl) or heterocyclyl (including alkyl-heterocyclyl), namely non-aromatic heterocyclyl (including non-aromatic alkyl-heterocyclyl), "substituted" should also be understood, unless otherwise specified, to mean substitution of the ring system of the cycloalkyl or alkyl-cycloalkyl, non-aromatic heterocyclyl or non-aromatic alkyl-heterocyclyl, providing spiro substitution and/or substitution with =O.

Moreover, with respect to cycloalkyl (including alkyl-cycloalkyl) or heterocyclyl (including alkylheterocyclyl), namely non-aromatic heterocyclyl (including non-aromatic alkyl-heterocyclyl), "substituted" should also be understood, unless otherwise specified, to mean substitution of the ring system of the cycloalkyl or alkyl-cycloalkyl, non-aromatic heterocyclyl or non-aromatic alkyl-heterocyclyl with =O.

A ring system is an organic system consisting of at least one ring of linked atoms, but also includes systems in which two or more rings of linked atoms are linked, where "linked" means that the respective rings have one (like a spiro structure), two or more common atoms that are a member or members of both linked rings.

The term "polycyclic ring system" means that the ring system is formed by two or more rings linked through at least one common atom.

Any compound which is an N-oxide of a compound according to the present invention, such as a compound according to general formula I defined above, should be understood to be also encompassed within the scope of the present invention.

The term "leaving group" refers to a molecular fragment that is removed with a pair of electrons in a heterolytic bond cleavage. Leaving groups can be anions or neutral molecules. Common anionic leaving groups are halides such as Cl-, Br-, and I-, and sulfonic acid esters such as tosylate (TsO-) or mesylate.

The term "salt" should be understood to mean any form of the active compound used according to the present invention in which it takes an ionic form, or is charged and conjugated with a counterion (cation or anion), or is in solution. This should also include complexes of the active compound with other molecules and ions, in particular complexes formed through ionic interactions.

The term "physiologically acceptable salt" means, in the context of the present invention, any salt that is physiologically tolerable (meaning that most of the time it is not toxic, in particular not caused by a counterion), when properly used for therapy, in particular when applied to or administered to humans and/or mammals.

These physiologically acceptable salts can be formed with cations or bases and in the context of the present invention are to be understood as meaning salts of at least one of the compounds used according to the present invention, usually a (deprotonated) acid, as an anion with at least one, preferably inorganic, cation which is physiologically tolerated, in particular when applied to and/or mammals. Salts of alkali metals and alkaline earth metals are particularly preferred, as well as salts with NH ₄ , in particular salts of (mono)- or (di)sodium, (mono)- or (di)potassium, magnesium or calcium.

Physiologically acceptable salts can also be formed with anions or acids and in the context of the present invention are to be understood as meaning salts of at least one of the compounds used according to the present invention as a cation with at least one anion which is physiologically tolerated, in particular when applied to humans and/or mammals. This is to be understood in particular in the context of the present invention as a salt formed with a physiologically tolerated acid, i.e. salts of a particularly active compound with inorganic or organic acids which are physiologically tolerated, in particular when applied to humans and/or mammals. Examples of physiologically tolerated salts of particular acids are salts of hydrochloric acid, hydrobromic acid, sulfuric acid, methanesulfonic acid, formic acid, acetic acid, oxalic acid, succinic acid, malic acid, tartaric acid, mandelic acid, fumaric acid, lactic acid or citric acid.

The compounds of the present invention may be presented in crystalline form or as free compounds, such as a free base or acid.

Any compound which is a solvate of a compound according to the present invention, such as a compound according to the general formula I defined above, is to be understood as also being encompassed within the scope of the present invention. Methods of solvation are generally known in the art. Suitable solvates are pharmaceutically acceptable solvates. The term "solvate" according to the present invention is to be understood as meaning any form of the active compound according to the present invention in which the compound has been attached by non-covalent binding to another molecule (usually a polar solvent). Particularly preferred examples include hydrates and alcoholates, such as methanolates or ethanolates.

Any compound which is a prodrug of a compound according to the present invention, such as a compound according to the general formula (I) defined above, is to be understood as also being encompassed within the scope of the present invention. The term "prodrug" is used in its broadest sense and encompasses those derivatives which are converted in vivo into the compounds according to the present invention. Such derivatives will be obvious to those skilled in the art and include, depending on the functional groups present in the molecule and without limitation, the following derivatives of the compounds according to the present invention: esters, amino acid esters, phosphoric acid esters, metal salts and sulfonic acid esters, carbamates and amides. Examples of well-known processes for preparing a prodrug of a particular active compound are known to those skilled in the art and can be found, for example, in Krogsgaard-Larsen et al. "Textbook of Drag design and Discovery" Taylor & Francis (April 2002).

Any compound which is an N-oxide of a compound according to the present invention, such as a compound according to general formula I defined above, should be understood to be also encompassed within the scope of the present invention.

Unless otherwise specified, the compounds of the present invention are also intended to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having these structures, except for the substitution of a hydrogen atom by deuterium or tritium, or the substitution of a carbon atom by a carbon enriched with ^13C or ^14C , or a nitrogen atom by a nitrogen enriched with ^15N , are within the scope of the present invention. In particular, this applies to the provisions described above such that any reference to hydrogen or any "H" in a formula will also encompass deuterium or tritium.

The compounds of formula (I), as well as their salts or solvates of the compounds, are preferably in a pharmaceutically acceptable or substantially pure form. Pharmaceutically acceptable means, inter alia, a form having a pharmaceutically acceptable level of purity without taking into account the usual pharmaceutical additives such as diluents and carriers and not containing substances that are considered toxic at normal dosage levels. The purity levels for the drug substance are preferably above 50%, more preferably above 70%, most preferably above 90%. In a preferred embodiment, for a compound of formula (I) or its salts, it is above 95%. This also applies to its solvates or prodrugs based on it.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

m is equal to 1, 2 or 3;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

n equals 1;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

p is 0, 1, 2, or 3;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R _x is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

r is 0 or 1;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

t is equal to 0 or 1;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

t equals 0;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy, -OR ₆ , -NR ₆ R ₆ ', -CN, cycloalkyl, aryl and heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, halogen, haloalkyl, haloalkoxy, -OR ₆ , -NR ₆ R ₆ ', -CN, cycloalkyl, aryl and heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, halogen, haloalkyl, -OR ₆ , -NR ₆ R ₆ ', -CN, cycloalkyl, aryl and heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, halogen, haloalkyl, haloalkoxy, -OR ₆ , -NR ₆ R ₆ ', -CN, cycloalkyl, aryl and heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, halogen, haloalkyl, -OR ₆ , -NR ₆ R ₆ ', -CN, cycloalkyl, aryl and heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, and haloalkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is selected from the group consisting of halogen, haloalkoxy, -OR ₆ and -CN;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is selected from the group consisting of cycloalkyl, aryl and heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁ is -NR ₆ R ₆ ';

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₂ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, halogen, haloalkyl, haloalkoxy and -OR ₇ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₂ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, halogen, haloalkyl, haloalkoxy and -OR ₇ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₂ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, halogen and -OR ₇ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₂ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, halogen, haloalkyl, haloalkoxy and -OR ₇ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₂ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, halogen, haloalkyl, haloalkoxy and -OR ₇ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or a corresponding salt or a corresponding solvate thereof. In a further embodiment, the compound according to the present invention of general formula (I) is a compound, wherein

R ₂ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, halogen and -OR ₇ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₃ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, halogen, haloalkyl, haloalkoxy and -OR ₈ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₃ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₄ is substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₄ is selected from the group consisting of substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₄ is selected from the group consisting of substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₅ and R ₅ ' are independently selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, haloalkyl, and haloalkoxy;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₅ and R ₅ ' are independently selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, haloalkyl, haloalkoxy; substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylheterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, haloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylheterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₆ and R ₆ ', taken together with the nitrogen atom to which they are attached, form a substituted or unsubstituted heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₆ ' is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₇ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₈ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted alkylcycloalkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted alkylcycloalkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₃ and R _13' are independently selected from hydrogen and unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₄ , R _14' and R _14'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₄ , R _14' and R _14'' are independently selected from hydrogen and unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₂₁ and R _21' are independently selected from hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₃₁ and R _31' are independently selected from hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₄₁ , R _41' and R _41'' are independently selected from hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₅₁ and R _51' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₅₁ and R _51' both represent hydrogen;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

alkyl, alkenyl or alkynyl in R ₁ when substituted are substituted by one or more substituents selected from -OR ₁₁ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₁ R _11' ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

cycloalkyl, aryl or heterocyclyl in R ₁ when substituted are substituted by one or more substituents selected from halogen, -R ₁₁ , -[CH ₂ ] _r OR ₁₁ , =O, -NO ₂ , -[CH ₂ ] _r NR ₁₁ R _11' , -NR ₁₁ C(O)R _11' , -NR ₁₁ S(O) ₂ R _11' , -S(O) ₂ NR ₁₁ R _11' , -NR ₁₁ C(O)NR _11' R _11'' , -SR ₁₁ , -S(O)R ₁₁ , -S(O) ₂ R ₁₁ , -CN, haloalkyl, haloalkoxy, -C(O)R ₁₁ , -C(O)OR ₁₁ , -C(O)NR ₁₁ R _11' , -OCH ₂ CH ₂ OR ₁₁ , -NR ₁₁ S(O) ₂ NR _11' R _11'' and -C(CH ₃ ) ₂ OR ₁₁ ; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

cycloalkyl, aryl or heterocyclyl in R ₁ , when substituted, are substituted by one or more substituents selected from halogen, -R ₁₁ , -[CH ₂ ] _r OR ₁₁ ,=O, -[CH ₂ ] _r NR ₁₁ R _11' , -S(O) ₂ R ₁₁ , -CN, haloalkyl, -C(O)R ₁₁ and -C(O)NR ₁₁ R _11' ; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or a corresponding salt or a corresponding solvate thereof.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

alkyl, alkenyl or alkynyl in R ₂ when substituted are substituted by one or more substituents selected from -OR ₂₁ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₂₁ R _21' ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

cycloalkyl in R ₂ , also in alkylcycloalkyl, when substituted is substituted by one or more substituents selected from halogen, -R ₂₁ , -[CH ₂ ] _r OR ₂₁ , =O, -NO ₂ , -[CH ₂ ] _r NR ₂₁ R _21' , -NR ₂₁ C(O)R _21' , -NR ₂₁ S(O) ₂ R _21' , -S(O) ₂ NR ₂₁ R _21' , -NR ₂₁ C(O)NR _21' R _21'' , -SR ₂₁ , -S(O)R ₂₁ , -S(O) ₂ R ₂₁ , -CN, haloalkyl, haloalkoxy, -C(O)R ₂₁ , -C(O)OR ₂₁ , -C(O)NR ₂₁ R _21' , -OCH ₂ CH ₂ OR ₂₁ , -NR ₂₁ S(O) ₂ NR _21' R _21'' and -C(CH ₃ ) ₂ OR ₂₁ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

alkyl, alkenyl or alkynyl in R ₃ when substituted are substituted by one or more substituents selected from -OR ₃₁ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₃₁ R _31' ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

alkyl, alkenyl or alkynyl in R ₄ when substituted are substituted by one or more substituents selected from -OR ₄₁ , halogen, -CN, haloalkyl, haloalkoxy, -NR ₄₁ R _41' ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

cycloalkyl, aryl or heterocyclyl in R ₄ when substituted are substituted by one or more substituents selected from halogen, -R ₄₁ , -[CH ₂ ] _r OR ₄₁ , =O, -NO ₂ , -[CH ₂ ] _r NR ₄₁ R _41' , -NR ₄₁ C(O)R _41' , -NR ₄₁ S(O) ₂ R _41' , -S(O) ₂ NR ₄₁ R _41' , -NR ₄₁ C(O)NR _41' R _41'' , -SR ₄₁ , -S(O)R ₄₁ , -S(O) ₂ R ₄₁ , -CN, haloalkyl, haloalkoxy, -C(O)R ₄₁ , -C(O)OR ₄₁ , -C(O)NR ₄₁ R _41' , -OCH ₂ CH ₂ OR ₄₁ , -NR ₄₁ S(O) ₂ NR _41' R _41'' and -C(CH ₃ ) ₂ OR ₄₁ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

cycloalkyl, aryl or heterocyclyl in R ₄ when substituted are substituted by one or more substituents selected from halogen, -R ₄₁ , -[CH ₂ ] _r OR ₄₁ , -CN and haloalkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

alkyl, alkenyl or alkynyl in R ₅ and R ₅₍ when substituted are substituted by one or more substituents selected from -OR ₅₁ , halogen, -CN, haloalkyl, haloalkoxy, -NR ₅₁ R _51' ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

alkyl, alkenyl or alkynyl in R ₅ and R _5' when substituted are substituted by one or more -OR ₅₁ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

alkyl, alkenyl or alkynyl, if substituted and not otherwise defined, are substituted with one or more substituents selected from -OR ₁₃ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₃ R _13' ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

aryl, heterocyclyl or cycloalkyl, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted and not otherwise defined, are substituted by one or more substituents selected from halogen, -R ₁₄ , -[CH ₂ ] _r OR ₁₄ , =O, -NO ₂ , -[CH ₂ ] _r NR ₁₄ R _14' , -NR ₁₄ C(O)R _14' , -NR ₁₄ S(O) ₂ R _14' , -S(O) ₂ NR ₁₄ R _14' , - NR ₁₄ C(O)NR _14' R _14'' , -SR ₁₄ , -S(O)R ₁₄ , S(O) ₂ R ₁₄ , -CN, haloalkyl, haloalkoxy, -C(O)R ₁₄ , -C(O)OR ₁₄ , C(O)NR ₁₄ R _14' , -OCH ₂ CH ₂ OR ₁₄ , -NR ₁₄ S(O) ₂ NR _14' R _14'' and -C(CH ₃ ) ₂ OR ₁₄ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

aryl, heterocyclyl or cycloalkyl, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if they are substituted and not otherwise defined, are substituted by one or more substituents selected from -R ₁₄ and -[CH ₂ ] _r NR ₁₄ R _14' ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

m is equal to 1, 2, 3, or 4;

and/or

n is 1 or 2; and/or

t is 0 or 1; and/or

r is 0, 1, 2, or 3; and/or

X is selected from the group consisting of a bond, -[CH ₂ ] _p -, -[CH ₂ ] _p NR _x [CH ₂ ] _q -, -[CH ₂ ] _p O[CH ₂ ] _q -, -[CH ₂ ] _p NR _x C(O)[CH ₂ ] _q - and -[CH ₂ ] _p NR _x CH(CH ₃ )-; and/or

p is 0, 1, 2, 3, or 4; and/or

q is 0, 1, 2, 3, or 4; and/or

R _x is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

and/or

R ₁ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy, -OR ₆ , -NR ₆ R _6' , -CN, cycloalkyl, aryl and heterocyclyl;

and/or

R ₂ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, halogen, haloalkyl, haloalkoxy and -OR ₇ ;

and/or

R ₃ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy and -OR ₈ ;

and/or

R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl;

and/or

R ₅ and R _5' are independently selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, haloalkyl and haloalkoxy;

and/or

R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, haloalkyl, haloalkoxy; substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylheterocyclyl;

and/or

R ₆₍ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

and/or

R ₆ and R _6' taken together with the nitrogen atom to which they are attached form a substituted or unsubstituted heterocyclyl;

and/or

R ₇ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

and/or

R ₈ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

and/or

R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyl cycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl;

and/or

R ₁₃ and R _13' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl; and/or

R ₁₄ , R _14' and R _14'' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl;

and/or

R ₂₁ and R _21' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

and/or

R ₃₁ and R _31' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

and/or

R ₄₁ , R _41' and R _41'' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl;

and/or

R ₅₁ and R _51' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, and substituted or unsubstituted C _2-6 alkynyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

m is equal to 1, 2 or 3;

and/or

n is equal to 1; and/or

t is 0 or 1; and/or

r is 0 or 1; and/or

X is selected from the group consisting of a bond, [CH ₂ ] _p -, -[CH ₂ ] _p NR _x [CH ₂ ] _q -, -[CH ₂ ] _p O[CH ₂ ] _q -, -[CH ₂ ] _p NR _x C(O)[CH ₂ ] _q - and -[CH ₂ ] _p NR _x CH(CH ₃ )-; and/or

p is 0, 1, 2, or 3; and/or

q is 0, 1, 2, 3, or 4; and/or

R _x is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; and/or

R ₁ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, halogen, haloalkyl, -OR ₆ , -NR ₆ R _6' , -CN, cycloalkyl, aryl and heterocyclyl;

and/or

R ₂ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, halogen and -OR ₇ ;

and/or

R ₃ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl;

and/or

R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heterocyclyl;

and/or

R ₅ and R _5' are independently selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl;

and/or

R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, haloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl, and substituted or unsubstituted alkylheterocyclyl;

and/or

R _6' is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; and/or

R ₆ and R _6' taken together with the nitrogen atom to which they are attached form a substituted or unsubstituted heterocyclyl; and/or

R ₇ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; and/or

R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted alkylcycloalkyl;

and/or

R ₁₃ and R _13' are independently selected from hydrogen and unsubstituted C _1-6 alkyl;

and/or

R ₁₄ and R _14' and R _14'' are independently selected from hydrogen and unsubstituted C _1-6 alkyl;

R ₄₁ , R _41' and R _41'' are independently selected from hydrogen and substituted or unsubstituted C _1-6 alkyl;

and/or

R ₅₁ and R ₅₁₍ simultaneously represent hydrogen;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₁ , as defined in any of the embodiments of the present invention,

alkyl in haloalkyl or haloalkoxy is C _1-6 alkyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably alkyl is methyl; and/or

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably C _1-6 alkyl is methyl, ethyl, isopropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

and/or

cycloalkyl is _C3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is _C3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably is _C3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; more preferably cycloalkyl is cyclopropyl;

and/or

aryl is selected from phenyl, naphthyl or anthracene; preferably is naphthyl and phenyl; more preferably aryl is phenyl;

and/or

heterocyclyl is a heterocyclic ring system with one or more saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur; preferably is a heterocyclic ring system with one or two saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur, more preferably selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, furan, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, isothiazole, tetrahydropyran, tetrahydrofuran, morpholine, thiomorpholine, indoline, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydroisoquinoline, tetrahydrothione pyridine, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, benzodioxolane, benzodioxane, carbazole, octahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspiroundecane, indolin-2-one and quinazoline; preferably heterocyclyl is pyridine, piperidine, pyrrolidine, piperazine, pyrazole, pyrimidine, isoxazole, isothiazole, imidazole, morpholine, thiomorpholine, tetrahydropyran, tetrahydrofuran and thiophene;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₂ , as defined in any of the embodiments of the present invention,

alkyl in alkylcycloalkyl, haloalkyl or haloalkoxy is C _1-6 alkyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl;

and/or

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl, preferably C _1-6 alkyl is methyl or ethyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C ₂ -6-alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

and/or

cycloalkyl is _C3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is _C3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably is _C3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; more preferably cycloalkyl is cyclopropyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₃ , as defined in any of the embodiments of the present invention,

alkyl in haloalkyl or haloalkoxy is C _1-6 alkyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl;

and/or

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably C _1-6 alkyl is methyl;

and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butane, pentyne, hexyne, isopropyne and isobutyne; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₄ , as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably C _1-6 alkyl is methyl, ethyl, isopropyl or isobutyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butane, pentyne, hexyne, isopropyne and isobutyne;

and/or

cycloalkyl is _C3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is _C3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably is _C3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

and/or

aryl is selected from phenyl, naphthyl or anthracene; preferably is naphthyl and phenyl; more preferably aryl is phenyl; and/or

heterocyclyl is a heterocyclic ring system with one or more saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur; preferably represents a heterocyclic ring system with one or two saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur, more preferably selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, furan, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, isothiazole, tetrahydropyran, tetrahydrofuran, morpholine, thiomorpholine, indoline, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydroisoquinoline, tetrahydrothienopyridine, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, benzodioxolane, benzodioxane, carbazole, octahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspiroundecane, indolin-2-one and quinazoline; preferably heterocyclyl is tetrahydropyran or pyridine; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or a corresponding salt or a corresponding solvate thereof.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₅ and R _5' , as defined in any of the embodiments of the present invention,

alkyl in haloalkyl or haloalkoxy is C _1-6 alkyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl;

and/or

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably C _1-6 alkyl is methyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butane, pentyne, hexyne, isopropyne and isobutyne; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₆ and R _6' , as defined in any of the embodiments of the present invention,

alkyl in alkylaryl, alkylheterocyclyl, alkylcycloalkyl, haloalkyl or haloalkoxy is C _1-6 alkyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably alkyl is methyl;

and/or

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably C _1-6 alkyl is methyl, ethyl or isopropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C ₂ -6-alkynyl is preferably selected from ethyne, propyne, butane, pentyne, hexyne, isopropyne and isobutyne;

and/or

cycloalkyl is _C3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is _C3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably is _C3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; more preferably cycloalkyl is cyclopropyl;

and/or

aryl is selected from phenyl, naphthyl or anthracene; preferably is naphthyl and phenyl; more preferably aryl is phenyl;

and/or

heterocyclyl is a heterocyclic ring system with one or more saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur; preferably represents a heterocyclic ring system with one or two saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur, more preferably selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, furan, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, isothiazole, tetrahydropyran, tetrahydrofuran, morpholine, thiomorpholine, indoline, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydroisoquinoline, tetrahydrothienopyridine, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, benzodioxolane, benzodioxane, carbazole, octahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspiroundecane, indolin-2-one and quinazoline; preferably heterocyclyl is piperidine, tetrahydropyran, morpholine, thiomorpholine, pyrrolidine or piperazine; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or a corresponding salt or a corresponding solvate thereof.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₇ , as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably C _1-6 alkyl is methyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butane, pentyne, hexyne, isopropyne and isobutyne; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₈ , as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably C _1-6 alkyl is methyl; and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butane, pentyne, hexyne, isopropyne and isobutyne; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to the general formula (I) is a compound wherein in R ₁₁ , R _11' and R _11'' defined in any of the embodiments of the present invention, alkyl in alkylaryl, alkylheterocyclyl, alkylcycloalkyl, haloalkyl or haloalkoxy is C _1-6 alkyl such as methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably alkyl is methyl;

and/or

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl, preferably C _1-6 alkyl is methyl or ethyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene; and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butane, pentyne, hexyne, isopropyne and isobutyne; and/or

cycloalkyl is _C3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is _C3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably is _C3-6 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl; more preferably cycloalkyl is cyclopropyl;

and/or

aryl is selected from phenyl, naphthyl or anthracene; preferably is naphthyl and phenyl; more preferably aryl is phenyl;

and/or

heterocyclyl is a heterocyclic ring system with one or more saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur; preferably represents a heterocyclic ring system with one or two saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur, more preferably selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, furan, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, isothiazole, tetrahydropyran, tetrahydrofuran, morpholine, thiomorpholine, indoline, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydroisoquinoline, tetrahydrothienopyridine, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, benzodioxolane, benzodioxane, carbazole, octahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspiroundecane, indolin-2-one and quinazoline; preferably heterocyclyl is triazole, oxadiazole or pyridine; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or a corresponding salt or a corresponding solvate thereof.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₁₃ and R _13' , as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably C _1-6 alkyl is methyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₁₄ , R _14' and R _14'' , as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably C _1-6 alkyl is methyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butyne, pentyne, hexyne, isopropyne and isobutyne;

and/or

cycloalkyl is _C3-8 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl or cyclooctyl; preferably is _C3-7 cycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl; more preferably is _C3- ecycloalkyl such as cyclopropyl, cyclobutyl, cyclopentyl or cyclohexyl;

and/or

aryl is selected from phenyl, naphthyl or anthracene; preferably it is naphthyl and phenyl; and/or

heterocyclyl is a heterocyclic ring system with one or more saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur; preferably represents a heterocyclic ring system with one or two saturated or unsaturated rings, of which at least one ring contains one or more heteroatoms in the ring selected from the group consisting of nitrogen, oxygen and/or sulfur, more preferably selected from oxazepane, pyrrolidine, imidazole, oxadiazole, tetrazole, azetidine, pyridine, pyrimidine, piperidine, piperazine, furan, benzofuran, benzimidazole, indazole, benzothiazole, benzodiazole, thiazole, isothiazole, tetrahydropyran, tetrahydrofuran, morpholine, thiomorpholine, indoline, triazole, isoxazole, pyrazole, thiophene, benzothiophene, pyrrole, pyrazine, pyrrolo[2,3b]pyridine, quinoline, quinolone, isoquinoline, tetrahydroisoquinoline, tetrahydrothienopyridine, phthalazine, benzo-1,2,5-thiadiazole, indole, benzotriazole, benzoxazole oxopyrrolidine, benzodioxolane, benzodioxane, carbazole, octahydro-ethanopyrrolo-pyridine, oxaspirodecane, oxadiazaspiroundecane, indolin-2-one and quinazoline, optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₂₁ , R _21' and R _21'' , as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butane, pentyne, hexyne, isopropyne and isobutyne; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₃₁ , R _31' and R _31'' , as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butane, pentyne, hexyne, isopropyne and isobutyne; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₄₁ , R _41' and R _41'' as defined in any of the embodiments of the present invention, C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl; more preferably C _1-6 alkyl is methyl; and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

C _2-6 -alkynyl is preferably selected from ethyne, propyne, butane, pentyne, hexyne, isopropyne and isobutyne; optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein in R ₅₁ and R _51' , as defined in any of the embodiments of the present invention,

C _1-6 alkyl is preferably selected from methyl, ethyl, propyl, butyl, pentyl, hexyl, isopropyl or 2-methylpropyl;

and/or

C _2-6 -alkenyl is preferably selected from ethylene, propylene, butylene, pentylene, hexylene, isopropylene and isobutylene;

and/or

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

m is 1, 2, 3, or 4; preferably m is 1, 2, or 3;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

n is 1 or 2; preferably n is 1;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

r is 0 or 1;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

r is 0, 1, 2, or 3; preferably g is 0 or 1;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

X is selected from the group consisting of the bond, -[CH ₂ ] _p -, -[CH ₂ ] _p NR _x [CH ₂ ] _q -, -[CH ₂ ] _p O[CH ₂ ] _q -, -[CH ₂ ] _p NR _x C(O)[CH ₂ ] _q - and -[CH ₂ ] _p NR _x CH(CH ₃ )-; preferably X is selected from the group consisting of a bond, -CH ₂ -, -CH ₂ CH ₂ -, -CH ₂ CH ₂ CH ₂ -, -CH ₂ O-, -CH ₂ OCH ₂ -, -NHC(O)CH ₂ -, -NHCH ₂ CH ₂ -, -CH ₂ NHCH ₂ -, -CH ₂ NH(CH ₂ ) ₂ -, -CH ₂ NH(CH ₂ ) ₃ -, -CH ₂ NH(CH ₂ ) ₄ -, -CH ₂ N(methyl)CH ₂ -, -CH ₂ N(iPr)CH ₂ -, -CH ₂ N(CH ₂ CF ₃ )CH ₂ -, -C ₂ NHCH(methyl)-, -CH ₂ N(methyl)CH ₂ CH ₂ -, -N(methyl)-, -N(methyl)CH ₂ -, -N(methyl)CH ₂ CH ₂ - and CH ₂ N _' isopropyl)CH ₂ -;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

p is 0, 1, 2, 3, or 4; preferably p is 0, 1, 2, or 3;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

q is equal to 0, 1, 2, 3, or 4;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R _x is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R _x is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; more preferably R _x is hydrogen or a substituted or unsubstituted group selected from methyl, ethyl, isopropyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₁ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy, -OR ₆ , -NR ₆ R _6' , -CN, cycloalkyl, aryl and heterocyclyl; preferably R ₁ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, halogen, haloalkyl, -OR ₆ , -NR ₆ R _6' , -CN, cycloalkyl, aryl and heterocyclyl; more preferably R ₁ is hydrogen, bromine, chlorine, -CN or a substituted or unsubstituted group selected from methyl, ethyl, isopropyl, -CF ₃ , -OH, methoxy, -O-isopropyl, -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -N(CH ₃ )(CH ₂ -cyclopropyl), -N(CH ₃ )(benzyl), -N(CH ₃ )(piperidine), -N(CH ₂ CF ₃ )(CH ₂ -tetrahydropyran), cyclopropyl, phenyl, pyridine, piperidine, pyrrolidine, piperazine, pyrimidine, pyrazole, isoxazole, isothiazole, imidazole, morpholine, thiomorpholine, tetrahydropyran, tetrahydrofuran and thiophene;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₂ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, halogen, haloalkyl, haloalkoxy and -OR ₇ ; preferably R ₂ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, halogen, haloalkyl, haloalkoxy and -OR ₇ ; more preferably R ₂ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, halogen and -OR ₇ ; even more preferably R ₂ is hydrogen, bromine, chlorine or a substituted or unsubstituted group selected from methyl, ethyl, cyclopropyl, -OH and methoxy;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₃ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy and -OR ₈ ; preferably R ₃ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, halogen, haloalkyl, haloalkoxy and -OR ₈ ; more preferably R ₃ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; even more preferably R ₃ is hydrogen or substituted or unsubstituted methyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; preferably R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; more preferably R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; even more preferably R ₄ is a substituted or unsubstituted group selected from methyl, ethyl, isopropyl, isobutyl, phenyl, pyridine and tetrahydropyran;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₅ and R _5' are independently selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, haloalkyl and haloalkoxy; preferably R ₅ and R _5' are independently selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, haloalkyl and haloalkoxy; more preferably R ₅ and R _5' are independently selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; even more preferably R ₅ and R _5' are independently selected from hydrogen or a substituted or unsubstituted group selected from methyl and methyl-OH;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, haloalkyl, haloalkoxy; substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyl cycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl; preferably R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkylhaloalkyl, haloalkoxy; substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyl cycloalkyl, substituted or unsubstituted alkyl aryl and substituted or unsubstituted alkyl heterocyclyl; more preferably R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl haloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyl cycloalkyl, substituted or unsubstituted alkyl aryl and substituted or unsubstituted alkyl heterocyclyl; even more preferably R ₆ is hydrogen or a substituted or unsubstituted group selected from methyl, isopropyl, benzyl, piperidine, -CH ₂ -cyclopropyl and -CH ₂ -tetrahydropyran;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₆₍ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R ₆₍ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; more preferably R ₆₍ is hydrogen or a substituted or unsubstituted group selected from methyl and -CH ₂ CF ₃ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₇ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R ₇ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; more preferably R ₇ is hydrogen or substituted or unsubstituted methyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₈ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R ₈ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkyl heterocyclyl; preferably R ₁₁ , R _11' and R _11" are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl; more preferably R ₁₁ , R _11' and R _11" are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted alkylcycloalkyl; even more preferably R ₁₁ , R _11' and R _11'' represent hydrogen or a substituted or unsubstituted group selected from methyl, ethyl, -CH ₂ -cyclopropyl, phenyl, pyridine, triazole and oxadiazole;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a further embodiment, the compound of the present invention of general formula (I) is a compound wherein

R ₁₃ and R _13' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl; preferably R ₁₃ and R _13' are independently selected from hydrogen and unsubstituted C _1-6 alkyl; more preferably R ₁₃ and R _13' are independently selected from the group consisting of hydrogen and unsubstituted methyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₁₄ , R _14' and R _14" are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; preferably R ₁₄ , R _14' and R _14" are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; more preferably R ₁₄ , R _14' and R _14" are independently selected from hydrogen and unsubstituted C _1-6 alkyl; even more preferably R ₁₄ , R _14' and R _14" are independently selected from hydrogen and unsubstituted methyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₂₁ and R _21' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R ₂₁ and R _21' are independently selected from hydrogen and substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₃₁ and R _31' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _1-6 alkynyl; preferably R ₃₁ and R _31' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

R ₄₁ , R _41' and R _41" are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R ₄₁ , R _41' and R _41" are independently selected from hydrogen and substituted or unsubstituted C _1-6 alkyl; more preferably R ₄₁ , R _41' and R _41" are independently selected from the group consisting of hydrogen and substituted or unsubstituted methyl;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to the general formula _' I) is a compound wherein

R ₅₁ and R _51' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R ₅₁ and R _51' are independently selected from hydrogen and substituted or unsubstituted C _1-6 alkyl; more preferably R ₅₁ and R _51' simultaneously represent hydrogen;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to the general formula _' I) is a compound wherein

cycloalkyl, aryl or heterocyclyl in R ₁ when substituted are substituted by one or more substituents selected from halogen, -R ₁₁ , -[CH ₂ ] _r OR ₁₁ , =O, -NO ₂ , -[CH ₂ ] _r NR ₁₁ R _11' , -NR ₁₁ C(O)R _11' , -NR ₁₁ S(O) ₂ R _11' , -S(O) ₂ NR ₁₁ R _11' , -NR ₁₁ C(O)NR _11' R _11'' , -SR ₁₁ , -S(O)R ₁₁ , -S(O) ₂ R ₁₁ , -CN, haloalkyl, haloalkoxy, -C(O)R ₁₁ , -C(O)OR ₁₁ , -C(O)NR ₁₁ R _11' , -OCH ₂ CH ₂ OR ₁₁ , -NR ₁₁ S(O) ₂ NR _11' R _11"' and -C(CH ₃ ) ₂ OR ₁₁ ; preferably cycloalkyl, aryl or heterocyclyl in R ₁ when substituted are substituted by one or more substituents selected from halogen, -R ₁₁ , -[CH ₂ ] _r OR ₁₁ ,=O, -[CH ₂ ] _r NR ₁₁ R _11' , -S(O) ₂ R ₁₁ , -CN, haloalkyl, -C(O)R ₁₁ and -C(O)NR ₁₁ R _11' ; more preferably cycloalkyl, aryl or heterocyclyl in R ₁ when substituted are substituted by one or more substituents selected from fluorine, chlorine, methyl, ethyl, -CF ₃ , -CN, -CH ₂ OH, -CH ₂ OCH ₃ , -OH-OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ -cyclopropyl, =O, -CH ₂ NHCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -C(O)CH ₃ , -C(O)NH ₂ , -C(O)N(CH ₃ ) ₂ , -S(O) ₂ CH ₃ , triazole, oxadiazole, phenyl and pyridine;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to the general formula _' I) is a compound wherein

cycloalkyl, aryl or heterocyclyl in R ₄ , when substituted, are substituted by one or more substituents selected from halogen, -R ₄₁ , -[CH ₂ ] _r OR ₄₁ , =O, -NO ₂ , -[CH ₂ ] _r NR ₄₁ R _41' , -NR ₄₁ C(O)R _41' , -NR ₄₁ S(O) ₂ R _41' , -S(O) ₂ NR ₄₁ R _41' , -NR ₄₁ C(O)NR _41' R _41'' , -SR ₄₁ , -S(O)R ₄₁ , -S(O) ₂ R ₄₁ , -CN, haloalkyl, haloalkoxy, -C(O)R ₄₁ , -C(O)OR ₄₁ , -C(O)NR ₄₁ R _41' , -OCH ₂ CH ₂ OR ₄₁ , -NR ₄₁ S(O) ₂ NR _41' R _41"' and -C _' CH ₃ ) ₂ OR ₄₁ ; preferably cycloalkyl, aryl or heterocyclyl in R ₄ , when substituted, are substituted by one or more substituents selected from halogen, -R ₄₁ , -[CH ₂ ] _r OR ₄₁ , -CN and haloalkyl; more preferably cycloalkyl, aryl or heterocyclyl in R ₄ , when substituted, are substituted by one or more substituents selected from fluorine, chlorine, -CH ₃ , -CF ₃ , -CN, -OH and -OCH ₃ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

alkyl, alkenyl or alkynyl in R ₅ and R _5' when substituted are substituted by one or more substituents selected from -OR ₅₁ , halogen, -CN, haloalkyl, haloalkoxy, -NR ₅₁ R _51' ; preferably alkyl, alkenyl or alkynyl in R ₅ and R _5' when substituted are substituted by one or more -OR ₅₁ ; more preferably alkyl, alkenyl or alkynyl in R ₅ and R _5' when substituted are substituted by one or more -OH;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to the general formula _' I) is a compound wherein

alkyl, alkenyl or alkynyl, if substituted and not otherwise defined, are substituted by one or more substituents selected from -OR ₁₃ , halogen, -CN, haloalkyl, haloalkoxy and -NR ₁₃ R _13' ; preferably alkyl, alkenyl or alkynyl, if substituted and not otherwise defined, are substituted by one or more substituents selected from -OR ₁₃ and -NR ₁₃ R _13' ; more preferably alkyl, alkenyl or alkynyl, if substituted and not otherwise defined, are substituted by one or more substituents selected from -OH, -OCH ₃ and -NHCH ₃ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to the general formula _' I) is a compound wherein

aryl, heterocyclyl or cycloalkyl, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted and not otherwise defined, are substituted by one or more substituents selected from halogen, -R ₁₄ , -[CH ₂ ] _r OR ₁₄ , =O, -NO ₂ , -[CH ₂ ] _r NR ₁₄ R _14' , -NR ₁₄ C(O)R _14' , -NR ₁₄ S(O) ₂ R _14' , -S(O) ₂ NR ₁₄ R _14' , -NR ₁₄ C(O)NR _14' R _14'' , -SR ₁₄ , -S(O)R ₁₄ , S(O) ₂ R ₁₄ , -CN, haloalkyl, haloalkoxy, -C(O)R ₁₄ , -C(O)OR ₁₄ , -C(O)NR ₁₄ R _14' , -OCH ₂ CH ₂ OR ₁₄ , -NR ₁₄ S(O) ₂ NR _14' R _14"' and -C(CH ₃ ) ₂ OR ₁₄ ; preferably aryl, heterocyclyl or cycloalkyl, also in alkylcycloalkyl, alkylaryl and alkyl heterocyclyl, if substituted and not otherwise defined, substituted by one or more substituents selected from -R ₁₄ and -[CH ₂ ] _r NR ₁₄ R _14' ; more preferably aryl, heterocyclyl or cycloalkyl, also in alkylcycloalkyl, alkylaryl and alkyl heterocyclyl, if substituted and not otherwise defined, substituted by one or more substituents selected from methyl and CH ₂ NHCH ₃ ;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In another preferred embodiment of the present invention, the compound according to general formula (I) is a compound wherein

m is 1, 2, 3, or 4; preferably m is 1, 2, or 3;

and/or

n is 1 or 2; preferably n is 1;

and/or

t is 0 or 1; and/or

p is 0, 1, 2, 3, or 4; preferably p is 0, 1, 2, or 3;

and/or

q is 0, 1, 2, 3, or 4; and/or

r is 0, 1, 2, or 3; preferably g is 0 or 1;

and/or

X is selected from the group consisting of the bond, -[CH ₂ ] _p -, -[CH ₂ ] _p NR _x [CH ₂ ] _q -, -[CH ₂ ] _p O[CH ₂ ] _q -, -[CH ₂ ] _p NR _x C(O)[CH ₂ ] _q - and -[CH ₂ ] _p NR _x CH(CH ₃ )-; preferably X is selected from the group consisting of a bond, -CH ₂ -, -CH ₂ CH ₂ -, -CH ₂ CH ₂ CH ₂ -, -CH ₂ O-, -CH ₂ OCH ₂ -, -NHC(O)CH ₂ -, -NHCH ₂ CH ₂ -, -CH ₂ NHCH ₂ -, -CH ₂ NH(CH ₂ ) ₂ -, -CH ₂ NH(CH ₂ ) ₃ -, -CH ₂ NH(CH ₂ ) ₄ -, -CH ₂ N(methyl)CH ₂ -, -CH ₂ N(iPr)CH ₂ -, -CH ₂ N(CH ₂ CF ₃ )CH ₂ -, -CH ₂ NHCH(methyl)-, -CH ₂ M(methyl)CH ₂ CH ₂ -, -N(methyl)-, -N(methyl)CH ₂ -, -N(methyl)CH ₂ CH ₂ - and CH ₂ N(isopropyl)CH ₂ -;

and/or

R _x is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R _x is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; more preferably R _x is hydrogen or a substituted or unsubstituted group selected from methyl, ethyl, isopropyl;

and/or

R ₁ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy, -OR ₆ , -NR ₆ R _6' , -CN, cycloalkyl, aryl and heterocyclyl; preferably R ₁ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, halogen, haloalkyl, -OR ₆ , -NR ₆ R _6' , -CN, cycloalkyl, aryl and heterocyclyl; more preferably R ₁ is hydrogen, bromine, chlorine, -CN or a substituted or unsubstituted group selected from methyl, ethyl, isopropyl, -CF ₃ , -OH, methoxy, -O-isopropyl, -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -N(CH ₃ )(CH ₂ -cyclopropyl), -N(CH ₃ )(benzyl), -N(CH ₃ )(piperidine), -N(CH ₂ CF ₃ )(CH ₂ -tetrahydropyran), cyclopropyl, phenyl, pyridine, piperidine, pyrrolidine, piperazine, pyrimidine, pyrazole, isoxazole, isothiazole, imidazole, morpholine, thiomorpholine, tetrahydropyran, tetrahydrofuran and thiophene;

and/or

R ₂ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, halogen, haloalkyl, haloalkoxy and -OR ₇ ; preferably R ₂ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted alkylcycloalkyl, halogen, haloalkyl, haloalkoxy and -OR ₇ ; more preferably R ₂ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, halogen and -OR ₇ ; even more preferably R ₂ is hydrogen, bromine, chlorine or a substituted or unsubstituted group selected from methyl, ethyl, cyclopropyl, -OH and methoxy; and/or

R ₃ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, halogen, haloalkyl, haloalkoxy and -OR ₈ ; preferably R ₃ is selected from the group consisting of hydrogen, substituted or unsubstituted d _-6 alkyl, halogen, haloalkyl, haloalkoxy and -OR ₈ ; more preferably R ₃ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; even more preferably R ₃ is hydrogen or substituted or unsubstituted methyl;

and/or

R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; preferably R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; more preferably R ₄ is selected from the group consisting of substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted aryl and substituted or unsubstituted heterocyclyl; even more preferably R ₄ is a substituted or unsubstituted group selected from methyl, ethyl, isopropyl, isobutyl, phenyl, pyridine, tetrahydropyran;

and/or

R ₅ and R _5' are independently selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, haloalkyl and haloalkoxy; preferably R ₅ and R _5' are independently selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, haloalkyl and haloalkoxy; more preferably R ₅ and R _5' are independently selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; even more preferably R ₅ and R _5' are independently selected from hydrogen or a substituted or unsubstituted group selected from methyl and methyl-OH;

and/or

R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, haloalkyl, haloalkoxy; substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl; preferably R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkylhaloalkyl, haloalkoxy; substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl; more preferably R ₆ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkylhaloalkyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl; even more preferably R ₆ is hydrogen or a substituted or unsubstituted group selected from methyl, isopropyl, benzyl, piperidine, -CH ₂ -cyclopropyl, -CH ₂ -tetrahydropyran;

and/or

R _6' is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R _6' is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; more preferably R _6' is hydrogen or a substituted or unsubstituted group selected from methyl and -CH ₂ CF ₃ ;

and/or

R6 and R6 _' taken together with the nitrogen atom to which they are attached form a substituted or unsubstituted heterocyclyl selected from the group consisting of morpholine, thiomorpholine, pyrrolidine and piperazine;

and/or

R ₇ is selected from the group consisting of hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R ₇ is selected from the group consisting of hydrogen and substituted or unsubstituted C _1-6 alkyl; more preferably R ₇ is hydrogen or substituted or unsubstituted methyl; and/or

R ₁₁ , R _11' and R _11'' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkyl cycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkyl heterocyclyl; preferably R ₁₁ , R _11' and R _11" are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted alkylcycloalkyl, substituted or unsubstituted alkylaryl and substituted or unsubstituted alkylheterocyclyl; more preferably R ₁₁ , R _11' and R _11" are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heterocyclyl and substituted or unsubstituted alkylcycloalkyl; even more preferably R ₁₁ , R _11' and R _11'' represent hydrogen or a substituted or unsubstituted group selected from methyl, ethyl, -CH ₂ -cyclopropyl, phenyl, pyridine, triazole and oxadiazole;

and/or

R ₁₃ and R _13' are independently selected from hydrogen, unsubstituted O _-6 alkyl, unsubstituted C _2-6 alkenyl and unsubstituted C _2-6 alkynyl; preferably R ₁₃ and R _13' are independently selected from hydrogen and unsubstituted C _1-6 alkyl; more preferably R ₁₃ and R _13' are independently selected from hydrogen and unsubstituted methyl;

and/or

R ₁₄ , R _14' and R _14" are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _2-6 alkenyl, unsubstituted C _2-6 alkynyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; preferably R ₁₄ , R _14' and R _14" are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted aryl, unsubstituted cycloalkyl and unsubstituted heterocyclyl; more preferably R ₁₄ , R _14' and R _14" are independently selected from hydrogen and unsubstituted C _1-6 alkyl; even more preferably R ₁₄ , R _14' and R _14" are independently selected from hydrogen and unsubstituted methyl;

and/or

R ₄₁ , R _41' and R _41" are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R ₄₁ , R _41' and R _41" are independently selected from hydrogen and substituted or unsubstituted C _1-6 alkyl; more preferably R ₄₁ , R _41' and R _41" are independently selected from hydrogen and substituted or unsubstituted methyl;

and/or

R ₅₁ and R _51' are independently selected from hydrogen, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _2-6 alkenyl and substituted or unsubstituted C _2-6 alkynyl; preferably R ₅₁ and R _51' are independently selected from hydrogen and substituted or unsubstituted C _1-6 alkyl; more preferably R ₅₁ and R _51' simultaneously represent hydrogen;

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In a preferred embodiment, m is 1, 2, or 3.

In a preferred embodiment, n is equal to 1.

In a preferred embodiment, t is 0 or 1.

In a preferred embodiment, t is equal to 0.

In a preferred embodiment, p is 0, 1, 2, or 3.

In a preferred embodiment, q is 0, 1, 2, 3, or 4.

In a preferred embodiment, r is 0 or 1.

In a preferred embodiment, X is selected from the group consisting of a bond, -CH ₂ -, -CH ₂ CH ₂ -, -CH ₂ CH ₂ CH ₂ -, -CH ₂ O-, -CH ₂ OCH ₂ -, -NHC(O)CH ₂ -, -NHCH ₂ CH ₂ -, -CH ₂ NHCH ₂ -, -CH ₂ NH(CH ₂ ) ₂ -, -CH ₂ NH(CH ₂ ) ₃ -, -CH ₂ NH(CH ₂ ) ₄ -, -CH ₂ N(methyl)CH ₂ -, -CH ₂ N(iPr)CH ₂ -, -CH ₂ N(CH ₂ CF ₃ )CH ₂ -, CH ₂ NHCH(methyl)-, -CH ₂ N(methyl)CH ₂ CH ₂ -, -N(methyl)-, -N(methyl)CH ₂ -, -N(methyl)CH ₂ CH ₂ - and -CH ₂ N(isopropyl)CH ₂ -.

In a preferred embodiment _, X _is selected from _the group consisting of _-CH2- , _-CH2CH2- and _-CH2CH2CH2- .

_In a preferred embodiment _, X is selected from the group consisting of _{-NHCH2CH2- ,} -CH2NHCH2- _, -CH2NH( _CH2 ) _2- , -CH2NH( _CH2 ) _3- , -CH2NH( _CH2 ) _4- , _{-CH2N (} methyl)CH2- _, -CH2N(iPr ₎ CH2-, -CH2N( _{CH2CF3 ) CH2-} , -CH2NHCH(methyl) _- , _-CH2N (methyl _{) CH2CH2-} , _-N (methyl) _- , -N(methyl) _CH2- , -N(methyl _{) CH2CH2-} and _-CH2N (isopropyl) _CH2- .

In a preferred embodiment, R _x is hydrogen or a substituted or unsubstituted group selected from methyl, ethyl, isopropyl.

In a preferred embodiment, R ₁ is hydrogen, bromine, chlorine, -CN or a substituted or unsubstituted group selected from methyl, ethyl, isopropyl, -CF ₃ , -OH, methoxy, -O-isopropyl, -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -N(CH ₃ )(CH ₂ -cyclopropyl), -N(CH ₃ )(benzyl), -N(CH ₃ )(piperidine), -N(CH ₂ CF ₃ )(CH ₂ -tetrahydropyran), cyclopropyl, phenyl, pyridine, piperidine, pyrrolidine, piperazine, pyrimidine, pyrazole, isoxazole, isothiazole, imidazole, morpholine, thiomorpholine, tetrahydropyran, tetrahydrofuran and thiophene.

In a preferred embodiment, R ₂ is hydrogen, bromine, chlorine, or a substituted or unsubstituted group selected from methyl, ethyl, cyclopropyl, -OH and methoxy.

In a preferred embodiment, R ₃ is hydrogen or substituted or unsubstituted methyl.

In a preferred embodiment, R ₄ is a substituted or unsubstituted group selected from methyl, ethyl, isopropyl, isobutyl, phenyl, pyridine and tetrahydropyran.

In a preferred embodiment, R ₅ and R _5' are independently selected from hydrogen or a substituted or unsubstituted group selected from methyl and methyl-OH.

In a preferred embodiment, R ₅ is selected from hydrogen, methyl and methyl-OH.

In a preferred embodiment, R _5' is hydrogen.

In a preferred embodiment, R ₅ is selected from hydrogen, methyl and methyl-OH, wherein R _5' is hydrogen.

In a preferred embodiment, R ₆ is hydrogen or a substituted or unsubstituted group selected from methyl, isopropyl, benzyl, piperidine, -CH ₂ -cyclopropyl, -CH ₂ -tetrahydropyran.

In a preferred embodiment, R _6' is hydrogen or a substituted or unsubstituted group selected from methyl and -CH ₂ CF ₃ .

In a preferred embodiment, R ₆ is hydrogen or a substituted or unsubstituted group selected from methyl, isopropyl, benzyl, piperidine, -CH ₂ -cyclopropyl, -CH ₂ -tetrahydropyran, wherein R _6' is hydrogen or a substituted or unsubstituted group selected from methyl and -CH ₂ CF ₃ .

In a preferred embodiment, R ₆ is hydrogen.

In a preferred embodiment, R ₆ is substituted or unsubstituted methyl.

In a preferred embodiment, R ₆ is substituted or unsubstituted isopropyl.

In a preferred embodiment, R ₆ is substituted or unsubstituted methyl, wherein R _6' is hydrogen or substituted or unsubstituted methyl.

In a preferred embodiment, R ₆ is substituted or unsubstituted methyl, wherein R _6' is hydrogen.

In a preferred embodiment, R ₆ and R _6' are simultaneously substituted or unsubstituted methyl.

In a preferred embodiment, R ₆ and R _6' are both hydrogen.

In a preferred embodiment, R ₆ is substituted or unsubstituted benzyl, wherein R ₆ ' is substituted or unsubstituted methyl.

In a preferred embodiment, R ₆ is substituted or unsubstituted -CH ₂ -cyclopropyl, wherein R ₆ ' is substituted or unsubstituted methyl.

In a preferred embodiment, R ₆ is substituted or unsubstituted -CH ₂ -tetrahydropyran, wherein R ₆ ' is substituted or unsubstituted -CH ₂ CF ₃ .

In a preferred embodiment, R ₆ and R ₆ ', taken together with the nitrogen atom to which they are attached, form a substituted or unsubstituted heterocyclyl selected from the group consisting of morpholine, thiomorpholine, pyrrolidine and piperazine.

In a preferred embodiment, R ₇ is hydrogen or substituted or unsubstituted methyl.

In a preferred embodiment, R ₁₁ , R ₁₁ ' and R ₁₁ '' are hydrogen or a substituted or unsubstituted group selected from methyl, ethyl, -CH ₂ -cyclopropyl, phenyl, pyridine, triazole and oxadiazole.

In a preferred embodiment, R ₁₁ is hydrogen or a substituted or unsubstituted group selected from methyl, ethyl, -CH ₂ -cyclopropyl, phenyl, pyridine, triazole and oxadiazole.

In a preferred embodiment, R ₁₁ ' is hydrogen or substituted or unsubstituted methyl.

In a preferred embodiment, R ₁₁ is hydrogen or a substituted or unsubstituted group selected from methyl, ethyl, -CH ₂ -cyclopropyl, phenyl, pyridine, triazole and oxadiazole, wherein R ₁₁ ' is hydrogen or substituted or unsubstituted methyl.

In a preferred embodiment, R ₁₁ is substituted or unsubstituted methyl, wherein R ₁₁ ' is hydrogen or substituted or unsubstituted methyl.

In a preferred embodiment,

R ₁₁ is substituted or unsubstituted methyl, where R ₁₁ ' is hydrogen.

In a preferred embodiment, R ₁₁ and R ₁₁ ' simultaneously represent hydrogen.

In a preferred embodiment, R ₁₁ and R ₁₁ ' are simultaneously substituted or unsubstituted methyl.

In a preferred embodiment, R ₁₃ and R ₁₃ ' are independently selected from hydrogen and unsubstituted methyl.

In a preferred embodiment, R ₁₃ is selected from hydrogen and unsubstituted methyl.

In a preferred embodiment, R ₁₃ ' is hydrogen.

In a preferred embodiment, R ₁₃ is hydrogen or unsubstituted methyl, wherein R ₁₃ ' is hydrogen.

In a preferred embodiment, R ₁₄ , R ₁₄ ' and R ₁₄ '' are independently selected from hydrogen and unsubstituted methyl.

In a preferred embodiment, R ₁₄ is unsubstituted methyl.

In a preferred embodiment, R ₁₄ is unsubstituted methyl, wherein R ₁₄ ' is hydrogen.

In a preferred embodiment, R ₄₁ , R ₄₁ ' and R ₄₁ '' are independently selected from hydrogen and substituted or unsubstituted methyl.

In a preferred embodiment, R ₄₁ is selected from hydrogen and substituted or unsubstituted methyl.

In a preferred embodiment, R ₅₁ is hydrogen.

In a preferred embodiment, cycloalkyl, aryl or heterocyclyl in R ₁ , when substituted, is substituted with one or more substituents selected from fluoro, chloro, methyl, ethyl, -CF ₃ , -CN, -CH ₂ OH, -CH ₂ OCH ₃ , -OH-OCH ₃ , -OCH ₂ CH ₃ , -OCH ₂ -cyclopropyl, =O, -CH ₂ NHCH ₃ , -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -C(O)CH ₃ , -C(O)NH ₂ , -C(O)N(CH ₃ ) ₂ , -S(O) ₂ CH ₃ , triazole, oxadiazole, phenyl and pyridine.

In a preferred embodiment, cycloalkyl, aryl or heterocyclyl in R ₄ , when substituted, is substituted with one or more substituents selected from fluoro, chlorine, -CH ₃ , -CF ₃ , -CN, -OH and -OCH ₃ .

In a preferred embodiment, alkyl, alkenyl or alkynyl in R ₅ and R ₅ ', when substituted, are substituted with one or more -OH.

In a preferred embodiment, alkyl, alkenyl or alkynyl, if substituted and not otherwise specified, are substituted with one or more substituents selected from -OH, -OCH ₃ and -NHCH ₃ .

In a preferred embodiment, aryl, heterocyclyl or cycloalkyl, also in alkylcycloalkyl, alkylaryl and alkylheterocyclyl, if substituted and not otherwise defined, are substituted by one or more substituents selected from methyl and CH ₂ NHCH ₃ .

In a preferred embodiment, the haloalkyl is _-CF3 .

In a preferred embodiment, the haloalkoxy is _OCF3 .

In a preferred embodiment, the compounds are selected from compounds that act as dual acting ligands for the α2δ subunit, in particular the α2δ-1 subunit, the voltage-dependent calcium channel and the σ ₁ receptor:

optionally in the form of one of the stereoisomers, preferably enantiomers or diastereomers, a racemate or in the form of a mixture of at least two stereoisomers, preferably enantiomers and/or diastereomers, in any ratio, or its corresponding salt, or its corresponding solvate.

In the following text, the phrase "a compound of the present invention" is used. It should be understood as any compound according to the present invention described above according to the general formula (I), (I'), (I ² '), (I ^2a '), (I ³ ') or (I ^3a ').

The compounds of the present invention represented by the above-described formula (I) may include enantiomers, depending on the presence of chiral centers, or isomers, depending on the presence of several bonds (e.g., Z, E). Individual isomers, enantiomers or diastereoisomers and mixtures thereof are within the scope of the present invention.

For clarity, the expression "a compound according to formula (I), wherein, for example, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', X, m, n and t are defined below in the detailed description" will (in the same way as the expression "a compound of formula (I), as defined in any of the claims, for example 1-8", occurring in the claims) refer to "a compound of formula (I)", where the definitions of the corresponding substituents R ₁ etc. (also from the cited claims) apply. Although, in addition, this will also mean (especially with respect to the claims) that also one or more of the provisions or conditions defined in the description (or applied in any of the cited claims, such as, for example, claim 1) can be applied to define the corresponding compound. Thus, a warning or disclaimer contained in, for example, claim 1 of a claim will also be used to define a compound of "formula (I) as defined in any of the corresponding linked claims, for example, 1-8".

In general, the experimental section below describes the methods. The starting materials are commercially available or can be obtained by traditional methods.

A preferred embodiment of the present invention is a process for preparing a compound according to formula (I), wherein, unless otherwise stated, R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', X, m, n and t have the meanings defined in the description.

In a particular embodiment, a method for preparing a compound according to formula (I) is provided, said method comprising treating a compound of formula (VI) in which A is -(CR ₅ R ₅ ') _m -R ₄ , and Y is a halogen atom,

a suitable boronic acid (or boronic acid ester) of formula (VII),

where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', X, m, n and t have the meanings defined in the description.

The reaction can be carried out in the presence of a suitable Pd containing catalyst such as Pd( _PPh3 ) ₄ , with a suitable _base such as _K2CO3 or _Na2CO3 , in a suitable solvent such as mixtures of dimethoxyethane and water or mixtures _of toluene, ethanol and water, at a suitable temperature, preferably with heating. Alternatively, the reactions can be carried out with microwave heating.

In another particular embodiment, a method for preparing a compound according to formula (I) is provided, said method comprising alkylating a compound of formula (Ia) in which A is hydrogen,

a suitable alkylating reagent of formula XI,

where T is -(CR ₅ R ₅ ') _m -R ₄ , and Z is a leaving group such as iodine, bromine, chlorine;

or alternatively via a reductive amination reaction using a suitable aldehyde of formula (XI) wherein Z is =O; wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', X, m, n and t are as defined herein. In a particular embodiment, there is provided a process for preparing a compound according to formula (I) wherein R ₁ is -CH ₂ NR ₆ R ₆ ', said process comprising reacting a compound of formula (VI) wherein A is -(CR ₅ R ₅ ') _m -R ₄ and Y is an acidic functional group,

with a suitable amine of formula (IX),

where R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R ₆ , R ₆ ', m, n and t have the meanings defined in the description.

The reaction can be carried out in the presence of a suitable coupling agent such as N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, in the presence of a base such as triethylamine, in a suitable solvent such as dimethylformamide, at a suitable temperature, preferably room temperature; followed by reduction using a suitable reducing agent such as _AlH3 , in a suitable solvent such as tetrahydrofuran, at a suitable temperature, preferably from 0°C to room temperature.

In a particular embodiment, a method for preparing a compound according to formula (I) is provided, wherein R ₁ is -CH ₂ NR ₆ R ₆ ', said method comprising reacting a compound of formula (VI) in which A is -(CR ₅ R ₅ ') _m -R ₄ , and Y is a halogen atom,

with a suitable salt in the form of potassium aminomethyl trifluoroborate of formula (X),

where R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R ₆ , R ₆ ', m, n and t have the meanings defined in the description.

The reaction can be carried out in the presence of a suitable Pd containing catalyst such as allyl palladium(II) chloride dimer, with a suitable base such as K ₃ PO ₄ and a suitable phosphine ligand such as dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine, in a suitable solvent such as a mixture of dioxane and water, at a suitable temperature, preferably 100°C.

In a particular embodiment, a method for preparing a compound according to formula (I) is provided, wherein R ₁ is -CH ₂ NR ₆ R ₆ ', said method comprising reacting a compound of formula (VIII) in which A is (CR ₅ R ₅ ') _m -R ₄ ,

with a suitable amine of formula (IX),

where R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R ₆ , R ₆ ', m, n and t have the meanings defined in the description.

The reaction can be carried out in the presence of a reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride, in a suitable solvent such as dichloromethane or methanol, optionally in the presence of an acid, preferably acetic acid, at a suitable temperature, preferably room temperature. Alternatively, the reactions can be carried out by heating with microwaves.

In a particular embodiment, a method for preparing a compound according to formula (I) is provided, wherein R ₁ is -CH ₂ NR ₆ R ₆ ', said method comprising alkylating a derivative of formula (Ib) in which A is hydrogen,

a suitable alkylating reagent of formula (XI),

where T is -(CR ₅ R ₅ ') _m -R ₄ , and Z is a leaving group such as iodine, bromine, chlorine;

or alternatively by a reductive amination reaction using a suitable aldehyde of formula XI wherein Z is =O;

where R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R ₆ , R ₆ ', m, n and t have the meanings defined in the description.

In a particular embodiment, a method for preparing a compound according to formula (I) is provided, said method comprising treating a compound of formula (VI) in which A is -(CR ₅ R ₅ ') _m -R ₄ , and Y is a halogen atom,

a suitable boronic acid (or boronic acid ester) of formula (VII),

or

said method comprises alkylating a compound of formula (Ia) in which A is hydrogen,

a suitable alkylating reagent of formula (XI),

where T is -(CR ₅ R ₅ ') _m -R ₄ , and Z is a leaving group such as iodine, bromine, chlorine;

or alternatively by a reductive amination reaction using a suitable aldehyde of formula XI wherein Z is =O;

and where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', X, m, n and t have the meanings defined in the description.

In a particular embodiment, a method for preparing a compound according to formula (I) is provided, wherein R ₁ is -CH ₂ NR ₆ R ₆ ', said method comprising:

carrying out a reaction of a compound of formula (VI) in which A is -(CR ₅ R ₅ ') _m -R ₄ and Y is an acidic functional group,

with a suitable amine of formula (IX),

or

carrying out a reaction of a compound of formula (VI) in which A is -(CR ₅ R ₅ ') _m -R ₄ and Y is a halogen atom,

with a suitable salt in the form of potassium aminomethyl trifluoroborate of formula (X),

or

carrying out a reaction of a compound of formula (VIII) in which A is -(CR ₅ R ₅ ') _m -R ₄ ,

with a suitable amine of formula (IX),

or

alkylation of a derivative of formula (Ib) in which A is hydrogen,

a suitable alkylating reagent of formula (XI),

where T is -(CR ₅ R ₅ ') _m -R ₄ , and Z is a leaving group such as iodine, bromine, chlorine;

or alternatively by a reductive amination reaction using a suitable aldehyde of formula (XI) wherein Z is =O;

where R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R ₆ , R ₆ ', m, n and t have the meanings defined in the description.

A particular embodiment of the present invention relates to the use of a compound of formula (Ia),

where R ₁ , R ₂ , R ₃ , X, n and t have the meanings defined herein and A is either hydrogen or a protecting group for an amino functional group (PG, such as benzyl or tert-butoxycarbonyl), to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (Ib),

where R ₂ , R ₃ , R ₆ , R ₆ ', n and t have the meanings defined herein and A is either hydrogen or a protecting group for an amino functional group (PG, such as benzyl or tert-butoxycarbonyl), to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (IIa),

where R ₃ , n and t have the meanings defined herein and A is either hydrogen or a protecting group for an amino functional group (PG, such as benzyl or t-butoxycarbonyl), to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (IIb),

where n and t have the meanings defined in the description and A is either hydrogen or a protecting group for an amino functional group (PG, such as benzyl or t-butoxycarbonyl) to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (IIIa),

where R is an alkyl group, to obtain compounds of formula (I). A particular embodiment of the present invention relates to the use of a compound of formula (IIIb),

where R ₃ has the meaning defined in the description and R is an alkyl group, to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (IV),

where R ₃ has the meaning defined herein and A is either hydrogen or a protecting group for an amino functional group (PG, such as benzyl or tert-butoxycarbonyl), to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (V),

where R ₂ has the meaning defined in the description and Y represents hydrogen, a halogen atom or an acidic functional group, to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (VI),

where R ₂ , R ₃ , n and t have the meanings defined in the description, Y is hydrogen, a halogen atom or an acid functional group, and A is either hydrogen or a protecting group for an amino functional group (PG, such as benzyl or tert-butoxycarbonyl), to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (VII),

where R ₁ has the meaning defined in the description, to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (VIII),

where R ₂ , R ₃ , n and t have the meanings defined herein and A is either hydrogen or a protecting group for an amino functional group (PG, such as benzyl or tert-butoxycarbonyl), to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (IX),

where R ₆ and R ₆ ' have the meanings defined in the description, to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (X),

where R ₆ and R ₆ ' have the meanings defined in the description, to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of a compound of formula (XI),

where T is -C(R ₅ R ₅ ') _m R ₄ , and Z is a halogen or an oxygen atom, and where R ₄ , R ₅ , R ₅ ' and m have the meanings defined herein, to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of compounds of formula (Ia), (Ib), (IIa), (IIb), (IIIa), (IIIb), (IV), (V), (VI), (VII), (VIII), (IX), (X) or (XI),

wherein R is an alkyl group, Y is hydrogen, a halogen atom, or an acid functional group, A is any of hydrogen, -C(R ₅ R ₅ ') _m R ₄ , or a protecting group for an amino functional group (PG, such as benzyl or tert-butoxycarbonyl), T is a group -C(R ₅ R ₅ ') _m R ₄ , and Z is a halogen or an oxygen atom, and wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R ₆ , R ₆ ', X, m, n and t have the meaning defined in the description, to obtain compounds of formula (I).

A particular embodiment of the present invention relates to the use of compounds of formula (Ia), (Ib), (VI) or (VIII),

wherein Y is hydrogen, a halogen atom or an acidic functional group, A is any of hydrogen, -C(R ₅ R ₅ ') _m R ₄ or a protecting group for an amino functional group (such as benzyl or tert-butoxycarbonyl), and wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R ₆ , R ₆ ', X, m, n and t have the meaning defined herein, to obtain compounds of formula (I).

If necessary, the resulting reaction products can be purified by conventional methods such as crystallization and chromatography. If the above-described methods for preparing the compounds of the present invention result in mixtures of stereoisomers, these isomers can be separated by conventional techniques such as preparative chromatography. If chiral centers are present, the compounds can be obtained in racemic form, or individual enantiomers can be obtained either by enantiospecific synthesis or by resolution.

One preferred pharmaceutically acceptable form of a compound of the present invention is a crystalline form, including such a form in a pharmaceutical composition. In the case of salts as well as solvates of the compounds of the present invention, the additional ionic moieties and the moieties representing the solvent should also be non-toxic. The compounds of the present invention may be present in various polymorphic forms, the present invention is intended to cover all such forms.

Another aspect of the present invention relates to a pharmaceutical composition, which comprises a compound of the present invention, described above in accordance with general formula I, or a pharmaceutically acceptable salt or stereoisomer thereof and a pharmaceutically acceptable carrier, adjuvant or carrier medium. Thus, the present invention provides pharmaceutical compositions comprising a compound of the present invention or a pharmaceutically acceptable salt or stereoisomers thereof together with a pharmaceutically acceptable carrier, adjuvant or carrier medium, for administration to a patient.

Examples of pharmaceutical compositions include any solid (tablets, pills, capsules, granules, etc.) or liquid (solutions, suspensions or emulsions) composition for oral, topical or parenteral administration.

In a preferred embodiment, the pharmaceutical compositions are presented in a form for oral administration, either solid or liquid. Suitable dosage forms for oral administration may be tablets, capsules, syrups or solutions and may contain conventional excipients known in the art, such as binding agents, for example syrup, acacia, gelatin, sorbitol, tragacanth or polyvinylpyrrolidone; fillers, for example lactose, sugar, corn starch, calcium phosphate, sorbitol or glycine; tabletting lubricants, for example magnesium stearate; disintegrants, for example starch, polyvinylpyrrolidone, sodium starch glycolate or microcrystalline cellulose; or pharmaceutically acceptable wetting agents, such as sodium lauryl sulfate.

Solid compositions for oral use can be prepared by conventional mixing, filling or tabletting processes. Repeated mixing operations can be used to distribute the active agent throughout these compositions using large amounts of excipients. Such operations are conventional in the art. For example, tablets can be prepared by wet or dry granulation and optionally coated according to methods well known in normal pharmaceutical practice, in particular enteric coating.

The pharmaceutical compositions may also be adapted for parenteral administration, such as sterile solutions, suspensions or lyophilized products in a suitable unit dosage form. Suitable auxiliary agents such as bulking agents, buffering agents or surface-active agents may be used.

The said compositions will be prepared using standard methods, such as those described in the Spanish and US Pharmacopoeias and similar reference sources or related thereto.

The compounds or compositions of the present invention may be administered by any suitable route, such as intravenous infusion, oral administration, intraperitoneal and intravenous administration. Oral administration is preferred due to patient convenience and the chronic nature of the diseases being treated.

In general, the effective amount of a compound of the present invention to be administered will depend on the relative potency of the compound selected, the severity of the disorder being treated, and the weight of the patient. However, the active compounds will generally be administered one or more times per day, such as 1, 2, 3 or 4 times per day, with typical total daily doses in the range of 0.1 to 1000 mg/kg/day.

The compounds and compositions of the present invention may be used with other drugs to provide combination therapy. The other drugs may be part of the same composition or may be presented as a separate composition for administration at the same time or at different times.

Another aspect of the present invention relates to the use of a compound according to the present invention or a pharmaceutically acceptable salt or isomer thereof in the manufacture of a medicament.

Another aspect of the present invention relates to a compound of the present invention according to the above-described general formula (I) or a pharmaceutically acceptable salt or isomer thereof for use as a drug for the treatment of pain. Preferably, the pain is moderate to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia. It may include mechanical allodynia or thermal hyperalgesia.

Another aspect of the present invention relates to the use of a compound according to the present invention in the manufacture of a medicament for the treatment or prevention of pain.

In a preferred embodiment, the pain is selected from moderate to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia, also preferably including mechanical allodynia or thermal hyperalgesia.

Another aspect of the present invention relates to a method for treating or preventing pain, wherein the method comprises administering to a patient in need of such treatment a therapeutically effective amount of the above-defined compound or a pharmaceutical composition based on it. Among the pain syndromes that can be treated are moderate to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia, wherein in this case mechanical allodynia or thermal hyperalgesia may also be included.

The present invention is illustrated below by means of examples. These illustrations are given only as an example and do not limit the general scope of the present invention.

General experimental part DESCRIPTION OF SYNTHESIS

Compounds of formula I can be prepared by the method described in Scheme 1,

where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ -5', R ₆ -6', X, m, n and t have the meanings defined in the description, R is an alkyl group, Y is hydrogen, a halogen atom or an acid functional group, A is either hydrogen or a protecting group for an amino functional group (PG, such as benzyl or tert-butoxycarbonyl) or T, where T is the group C(R ₅ R ₅ ') _m R ₄ , and Z is halogen or an oxygen atom.

The method can be carried out as described below.

Step 1. The compound of formula IV can be prepared by treating a carbonyl derivative of formula IIa with an appropriate alkoxy-N,N,N',N'-tetramethylmethanediamine derivative of formula IIIa (step 1a) or by treating a carbonyl derivative of formula IIb with an appropriate 1,1-dialkoxy-1-N,N-dimethylalkylamine derivative of formula IIIb (step 1b) at a suitable temperature, preferably in the range from 80°C to 100°C.

Step 2. A compound of formula VI can be prepared by treating a compound of formula IV with a suitable 3-aminopyrazole derivative of formula V in a suitable solvent such as acetic acid at a suitable temperature, preferably in the range from 50°C to reflux temperature.

Step 3. A compound of formula Ia can be prepared by treating a compound of formula VI, in which Y is a halogen atom, with _a suitable boronic acid (or boronic ester) of formula VII in the presence of a suitable Pd-containing catalyst such as Pd( _PPh3 ) ₄ , using a suitable base such as _K2CO3 or _Na2CO3 , in _a suitable solvent such as mixtures of dimethoxyethane and water or mixtures of toluene, ethanol and water, at a suitable temperature, preferably with heating. Alternatively, the reactions can be carried out with microwave heating.

Step 4. A compound of formula VIII can be prepared by treating a compound of formula VI in which Y is a hydrogen atom with _POCl3 in a suitable solvent such as dimethylformamide at a suitable temperature, preferably at 0°C. Alternatively, a compound of formula VIII can be prepared by treating a compound of formula VI in which Y is a halogen atom with (E)-4,4,5,5-tetramethyl-2-styryl-1,3,2-dioxaborolane in the presence of a suitable Pd containing catalyst such as Pd(dppf) _Cl2 using a suitable base such as _Na2CO3 in _a suitable solvent such as mixtures of toluene, ethyl acetate and water at a suitable temperature, preferably 90°C; followed by treatment with a suitable oxidizing agent such as _NaIO4 , in the presence of a suitable catalyst such as _OsO4 , in a suitable solvent such as mixtures of acetone and water, at a suitable temperature, preferably room temperature.

Step 5. A compound of formula Ib may be prepared by treating a compound of formula VIII with a suitable amine of formula IX in the presence of a reducing agent such as sodium triacetoxyborohydride or sodium cyanoborohydride in a suitable solvent such as dichloromethane or methanol, optionally in the presence of an acid, preferably acetic acid, at a suitable temperature, preferably room temperature. Alternatively, the reactions may be carried out by heating with microwaves.

Step 6. Alternatively, a compound of formula Ib can be prepared by reacting a compound of formula VI, wherein Y is an acidic functional group, with a suitable amine of formula IX in the presence of a suitable coupling agent such as N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, in the presence of a base such as triethylamine, in a suitable solvent such as dimethylformamide, at a suitable temperature, preferably room temperature; followed by reduction using a suitable reducing agent such as _AlH3 , in a suitable solvent such as tetrahydrofuran, at a suitable temperature, preferably in the range from 0°C to room temperature.

Step 7. Alternatively, a compound of formula Ib can be prepared by reacting a compound of formula VI in which Y is a halogen atom with a suitable potassium aminomethyl trifluoroborate salt of formula X in the presence of a suitable Pd containing catalyst such as allyl palladium(II) chloride dimer, using a suitable base such as K ₃ PO ₄ and a suitable phosphine ligand such as dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine, in a suitable solvent such as a mixture of dioxane and water, at a suitable temperature, preferably 100°C.

In addition, the group C(R ₅ R ₅ ') _m R ₄ (T) can be incorporated at any stage of the synthesis by converting a derivative where A is a protecting group, PG, into a derivative where A is H, followed by a substitution reaction (see Scheme 1). Removal of the protecting group PG can be accomplished as follows:

if the protecting group is benzyl, the removal of the protecting group can be carried out in the presence of a suitable Pd containing catalyst, such as 10% Pd/C, using a suitable hydrogen source, such as ammonium formate, in a suitable solvent, such as ethanol, at a suitable temperature, such as 85°C;

If the protecting group is Boc (tert-butoxycarbonyl), removal of the protecting group can be accomplished by adding a solution of a strong acid such as HCl in a suitable solvent such as diethyl ether, 1,4-dioxane or methanol, or by using trifluoroacetic acid in dichloromethane.

The T group can then be introduced by any suitable reaction such as:

an alkylation reaction with a suitable alkylating reagent of formula XI as shown in Scheme 1, wherein Z is a leaving group such as iodine, bromine, chlorine, or alternatively an epoxide ring opening occurs; in a suitable solvent such as acetonitrile, dichloromethane or dimethylacetamide; in the presence of an organic base such as triethylamine or diisopropylethylamine, or an inorganic Lewis acid such as LiClO ₄ ; at a suitable temperature in the range from room temperature to reflux temperature, or alternatively the reactions can be carried out under microwave heating.

a reductive amination reaction using a suitable aldehyde of formula XI, wherein Z is =O, using the conditions described above in step 5. In addition, certain compounds of the present invention can also be prepared by interconversion of functional groups between compounds of formula Ia, Ib, or any of the intermediates shown in scheme 1. The following transformations are examples of transformations that can be carried out.

The halogen atom can be introduced using a suitable halogenating agent such as NBS or NIS, in the presence of benzoyl peroxide, in a suitable solvent such as carbon tetrachloride, at a suitable temperature, preferably 70°C.

The halogen atom can be converted into a hydroxyl group using a suitable borylation agent such as bis(pinacolato)diboron in the presence of a suitable Pd containing catalyst such as Pd(dppf) _FeCl2 using a suitable base such as KOAc in a suitable solvent such as dioxane at a suitable temperature, preferably at 115°C; followed by oxidation using a suitable oxidizing agent such as hydrogen peroxide in a suitable solvent such as acetic acid at a suitable temperature, preferably in the range from 0°C to room temperature.

The halogen atom can be converted into an alkylamino group using a suitable alkylamine in the presence _of a suitable catalyst such as _Pd2dba3 or _CuI , optionally in the presence of (S)-proline, using a suitable base such as ^KOtBu or _K2CO3 , in a suitable solvent such as toluene or dimethyl sulfoxide, at a suitable temperature, preferably 100°C. Alternatively, the reactions can be carried out by heating with microwaves.

- The halogen atom can be converted into a CN group using a suitable cyanide source such as _K4 [Fe(CN) ₆ ] _⋅2H2O in the presence of a suitable Pd containing catalyst such as Pd(OAc) ₂ and a suitable ligand such as 1,1'-bis(diphenylphosphino)ferrocene using a suitable base such as _Na2CO3 in a suitable solvent such as N-methylpyrrolidone at a suitable temperature, preferably 120°C. Alternatively, the reactions can be carried out by heating with microwaves.

- The halogen atom can be converted into a pyrimidine ring using a suitable stannane reagent such as tributyl(1-ethoxyvinyl)stannane in the presence of a suitable Pd containing catalyst such as _PdCl2 ( _PPh3 ) ₂ in a suitable solvent such as toluene at a suitable temperature, preferably at 80°C; followed by the conditions described in step 1a and by treatment with a suitable formimidamide source such as formimidamide acetate at a suitable temperature, preferably at 130°C.

- The hydroxyl or amino group can be alkylated using a suitable alkylating agent such as an alkyl halide or alkyl trifluoromethanesulfonate, in the presence of a base such as triethylamine or NaH, in a suitable solvent such as dichloromethane or dimethylformamide, at a suitable temperature, preferably in the range from room temperature to 85°C.

- The hydroxyl group may be arylated using a suitable aryl alcohol using a suitable coupling agent such as diisopropyl azodicarboxylate, using a suitable phosphine such as triphenylphosphine, in a suitable solvent such as toluene, at a suitable temperature, preferably 100°C.

- The double bond can be reduced using a suitable hydrogen source, such as a hydrogen gas atmosphere, using a suitable Pd-containing catalyst, such as Pd(OH) ₂ , in a suitable solvent, such as methanol, at a suitable temperature, preferably room temperature.

- The carbonyl group can be reduced to an alcohol using a suitable reducing agent such as sodium borohydride in a suitable solvent such as tetrahydrofuran at a suitable temperature, preferably in the range from 0°C to room temperature.

- The carbonyl group can be converted into a nitroethyl group using nitromethane with a suitable base such as methylamine in a suitable solvent such as methanol at a suitable temperature, preferably at 60°C; followed by reduction using a suitable reducing agent such as sodium borohydride in a suitable solvent such as methanol at a suitable temperature, preferably room temperature.

- The nitro group can be reduced to an amino group using a suitable reducing agent such as Zn or a hydrogen-Raney nickel mixture, optionally in the presence of CaCl ₂ , in a suitable solvent such as methanol or mixtures of ethanol and water, at a suitable temperature, preferably in the range from 40°C to 80°C.

In some of the processes described above, it may be necessary to protect the reactive or labile groups present using suitable protecting groups such as, for example, acetyl, allyl, Alloc (allyloxycarbonyl), Boc (tert-butoxycarbonyl) or benzyl to provide protection of amino groups and conventional silyl protecting groups to provide protection of the hydroxyl group. The procedures for introducing and removing such protecting groups are well known in the art and detailed descriptions can be found in the literature.

In addition, the compound of formula I can be obtained in enantiopure form by resolution of the racemic mixture either by chiral preparative HPLC or by crystallization of a diastereomeric salt or co-crystal. Alternatively, the resolution step can be carried out in the preceding step using any suitable intermediate.

The compounds of formulae IIa, IIb, IIIa, IIIb, V, VII, IX, X and XI used in the processes disclosed above are commercially available or can be synthesized according to conventional procedures described in the literature and illustrated in the synthesis of some intermediates.

Examples

The following abbreviations were used in the examples.

AcOH: acetic acid

ACN: acetonitrile

anhydrous: waterless

aq.: water

Boc ₂ O: di-tert-butyl dicarbonate

Chx: cyclohexane

Conc.: concentrated

DCM: dichloromethane

DEA: diethylamine

DIAD: diisopropyl azodicarboxylate

DIPEA: N,N-diisopropylethylamine

DMA: N,N-dimethylacetamide

DME: dimethoxyethane

DMF: dimethylformamide

DMAP: Dimethylaminopyridine

DMSO: dimethyl sulfoxide

EDC.HCl: N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride

Et ₂ O: diethyl ether

EtOAc: ethyl acetate

EtOH: ethanol

h: hour(s)

HOBt: 1-hydroxybenzotriazole

HPLC: High Performance Liquid Chromatography

iPrOH: isopropanol

LDA: lithium diisopropylamide

MeOH: methanol

MS: mass spectrometry

min: minutes

MW: microwave treatment

NBS: N-bromosuccinimide

NIS: N-iodosuccinimide

NMP: N-methyl-2-pyrrolidone

quant.: quantitative

Rt: retention time

Rf: retention factor

r.t.: room temperature

sat.: saturated

sol.: solution

TEA: triethylamine

TFA: trifluoroacetic acid

THF: tetrahydrofuran

TLC: thin layer chromatography

XPhos: 2-dicyclohexylphosphino-2',4',6'-triisopropylbiphenyl

Wt: weight

The following methods were used to determine HPLC-MS spectra.

METHOD A

Column Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 µm; flow rate 0.61 ml/min; A: NH ₄ HCO ₃ 10 mM; B: ACN; gradient: 0.3 min in 98% A, from 98% A to 5% A in 2.52 min, isocratic elution 1.02 min in 5% A.

METHOD B

Column Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 µm, flow rate 0.60 ml/min; A: 10 mM NH ₄ HCO ₃ , B: ACN; gradient: 0.3 min 90% A, from 90% A to 5% A in 2.7 min, isocratic elution 0.7 min 5% A.

METHOD C

Column Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 µm, flow rate 0.61 ml/min; A: 10 mM NH ₄ HCO ₃ , B: ACN; gradient 0.3 min 98% A, from 98% A to 0% A in 2.7 min; isocratic elution 2 min 0% A.

METHOD D

XBridge® Shield RP18 column 4.6 x 50 mm, 3.5 µm, flow rate 1.6 mL/min at 50°C; A: 10 mM NH ₄ HCO ₃ /25% w/w NH ₄ OH (99.8:0.12) pH 9, B: ACN; gradient 0.5 min 95% A, from 95% to 0% A in 3.5 min; isocratic elution 1.5 min 0% A.

METHOD E

XBridge® Shield RP18 column, 4.6 x 50 mm, 3.5 µm, flow rate 1.5 mL/min at 30°C; A: 10 mM NH ₄ HCO ₃ /25% w/w NH ₄ OH (99.8:0.12) pH 9, B: ACN; gradient 0.5 min 95% A, from 95% to 0% A in 4.5 min; isocratic elution 1.5 min 0% A.

METHOD F

Column Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 μm, flow rate 0.61 mL/min; A: 10 mM NH ₄ HCO ₃ , B: ACN, C: MeOH + 0.1% formic acid; gradient 0.3 min 98% A, from 98% A to 0:95:5 A:B:C in 2.7 min; 0:95:5 A:B:C to 100% B in 0.1 min; isocratic elution 2 min 100% B.

METHOD G

Column Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 m, flow rate 0.6 ml/min; H ₂ O + 0.2% v/v NH ₃ , B: ACN; gradient from 95% A to 5% A in 4 min, from 5% A to 0% A in 0.2 min, isocratic elution 0.48 min 0% A.

METHOD N

Column Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 µm, flow rate 0.61 ml/min; A: 10 mM NH ₄ HCO ₃ , B: ACN; gradient 0.3 min 98% A, from 98% A to 100% B in 2.65 min; isocratic elution 2.05 min 100% B.

METHOD I

XBridge® Shield RP18 column, 4.6 x 50 mm, 3.5 µm, flow rate 1.5 mL/min at 30°C; A: 10 mM NH ₄ HCO ₃ /25% w/w NH ₄ OH (99.8:0.12) pH 9, B: ACN; gradient 0.5 min 50% A, from 50% to 5% A in 4.5 min; isocratic elution 1.5 min 5% A.

METHOD J

Column Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 µm, flow rate 0.6 mL/min; _H2O + 0.1% v/v TFA, B: ACN; gradient from 95% A to 5% A in 4 min, from 5% A to 0% A in 0.2 min, isocratic elution 0.48 min 0% A.

METHOD K

Analytical column CHIRALPACK® IG-3. 4.6 x 150 mm, 3 µm, flow rate 1.0 mL/min at 25°C; A: 20 mM _{NH4HCO3 /} aq. pH 9 (with DEA), B: ACN; isocratic elution 15 min: a) (20% A); b) (25% A); c) (30% A); d) (35% A); e) (40% A); f) (55% A); g) (60% A).

METHOD L

CHIRALPACK® IC-3 analytical column. 4.6 x 150 mm, 3 µm, flow rate 1.0 ml/min at 25°C; A: 20 mM _{NH4HCO3 /} aq. pH 9 (with DEA), B: ACN; isocratic elution 15 min 30% A.

METHOD M

Analytical column CHIRALCEL® OJ-3R. 4.6 x 150 mm, 3 µm, flow rate 1.0 ml/min at 25°C; A: 20 mM NH ₄ HCO ₃ / aq. pH 9 (with DEA), B: ACN; isocratic elution 15 min 70% A.

METHOD N

Column Acquity UPLC BEH C18, 2.1 x 50 mm, 1.7 µm, flow rate 0.61 ml/min; A: 10 mM NH ₄ HCO ₃ , pH 10.6, B: ACN; gradient 0.3 min 98% A, from 98% A to 0% A in 2.7 min; isocratic elution 2 min 0% A.

Synthesis of examples

Example 1. 7-(1-Benzylpiperidin-3-yl)-2-bromopyrazolo[1,5-a]pyrimidine

Stage a. 1-(1-Benzylpiperidin-3-yl)-3-(dimethylamino)prop-2-en-1-one

1-(1-Benzylpiperidin-3-yl)ethanone (1.67 g, 7.7 mmol) and 1-tert-butoxy-N,N,N',N'-tetramethylmethanediamine (1.47 g, 8.5 mmol) were stirred at 80 °C for 16 h. The reaction mixture was cooled and evaporated to dryness under vacuum to give the title compound (1.96 g, yield: 94%).

HPLC-MS (Method A): Rt: 1.44 minutes; ESI+-MS m/z: 273.2 (M+1).

Step b. The title compound

5-Bromo-1H-pyrazol-3-amine (535 mg, 3.3 mmol) was added to a solution of the compound obtained in step a (900 mg, 3.3 mmol) in AcOH (10 mL) and the solution was stirred at 100 °C for 16 h. The mixture was cooled and the solvent was evaporated in vacuo. 10% aq. NaOH solution was added and the product was extracted with EtOAc, the combined organic layers were washed with brine, dried over _{anhydrous Na2SO4} , filtered and concentrated to dryness. The crude product was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound (612 mg, yield: 50%).

HPLC-MS (Method A): Rt, 2.32 minutes; ESI+-MS m/z: 371 [M+H] ⁺ .

This method was used to prepare Examples 2-9 using suitable starting materials.

Example 10 7-(1-Benzylpiperidin-3-yl)-3-bromo-2-methylpyrazolo[1,5-a]pyrimidine

NBS (697 mg, 3.9 mmol) and benzoyl peroxide (94 mg, 0.4 mmol) were added to a solution of the compound obtained in Example 3 (1.0 g, 3.3 mmol) in CCU (150 mL) and the resulting mixture was heated at 70 °C for 16 h. Upon completion, the mixture was cooled and the solvent was evaporated under vacuum. The residue was quickly filtered through a pad of silica using Chx:EtOAc (95:5) and concentrated to dryness. The crude product was purified by flash chromatography on silica gel, Chx:EtOAc, to give the title compound (670 mg, yield: 53%).

HPLC-MS (Method A): Rt, 2.39 minutes; ESI+-MS m/z: 385.1 [M+H] ⁺ .

This method was used to obtain Example 11 using suitable starting materials:

Example 12 7-(1-Benzylpiperidin-3-yl)-2-phenylpyrazolo[1,5-a]pyrimidine

A microwave tube was filled with the compound obtained in Example 1 (200 mg, 0.54 mmol), phenylboronic acid (99 mg, 0.8 mmol), _{K2CO3 (} 223 mg, 1.6 mmol), Pd( _PPh3 ) ₄ (12 mg, 0.01 mmol) and DME: _H2O (1:1) (6 mL) and degassed by bubbling with argon for 5 min. The reaction mixture was heated under microwave irradiation at 130 °C for 20 min. The suspension was diluted with EtOAc and washed with aq. _saturated NaHCO3 solution. The organic layer was dried over _{anhydrous Na2SO4} , filtered and the solvent was removed under vacuum. The residue was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound (158 mg, yield: 80%).

HPLC-MS (Method A): Rt, 2.56 min; ESI+-MS m/z: 369.3 [M+H] ⁺ .

This method was used to prepare Examples 13-60 using suitable starting materials.

Example 61

Step a. tert-Butyl ((1-(3-bromophenyl)-1H-1,2,3-triazol-4-yl)methyl)(methyl)carbamate

TEA (0.92 mL, 6.6 mmol) and di-tert-butyl dicarbonate (450 mg, 2.1 mmol) were added portionwise to a solution of 1-(1-(3-bromophenyl)-1H-1,2,3-triazol-4-yl)-N-methylmethanamine hydrochloride (500 mg, 1.6 mmol) in DCM (5 mL) and the reaction mixture was stirred at rt for 16 h. The resulting mixture was washed with aq. sat. _NaHCO3 , water and brine. The organic layer was dried over anhydrous _Na2SO4 , _filtered and concentrated to give the title compound (735 mg, yield: quant.).

HPLC-MS (Method A): Rt: 2.11 minutes; ESI+-MS m/z: 367.1 (M+1).

Step b. (3-(4-(((tert-Butoxycarbonyl)(methyl)amino)methyl)- 1H- 1,2,3-triazol-1-yl)phenyl)boronic acid

To a solution of the compound obtained in step a (580 mg, 1.6 mmol), bis(pinacolato)diboron (802 mg, 3.2 mmol) and KOAc (465 mg, 4.7 mmol) in anhydrous DMSO (25 mL) was added Pd(dppf)FeCl ₂ (115 mg, 0.16 mmol) under argon atmosphere and the mixture was heated at 90 °C for 16 h. The mixture was dissolved with EtOAc:Et ₂ O (1:1) and washed with aq. saturated NaHCO ₃ solution. The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica gel, Chx:EtOAc, to give the title compound (690 mg, yield: quant.).

HPLC-MS (Method A): Rt: 1.52 minutes; ESI+-MS m/z: 333.1 (M+1).

Stage c. tert-Butyl-((1-(3-(7-(1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)phenyl)-1H-1,2,3-triazol-4-yl)methyl)(methyl)carbamate

Starting from the compound obtained in Example 10 (70 mg, 0.18 mmol) and the compound obtained in step b (90 mg, 0.27 mmol), and according to the procedure described in Example 12, the title compound was obtained (58 mg, yield: 44%).

HPLC-MS (Method A): Rt: 2.71 minutes; ESI+-MS m/z: 593.5 (M+1).

Stage d. Title compound

TFA (0.5 mL) was added to a solution of the compound obtained in step c (58 mg, 0.08 mmol) in DCM (5 mL) and the mixture was stirred at rt for 16 h. The reaction mixture was basified with aq. saturated _NaHCO3 and the mixture _was extracted with DCM. The combined organic layers were washed with brine, dried over anhydrous _Na2SO4 , filtered and concentrated to dryness. The crude product was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound (22 mg, yield: 57%).

HPLC-MS (Method A): Rt, 2.06 min; ESI+-MS m/z: 493.3 [M+H] ⁺ .

This method was used to prepare Example 62 using the appropriate starting materials:

Example 63. 7-(1-(2-Fluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidine

Step a. 2-Methyl-7-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidine

In a Radley tube, the compound obtained in Example 3 (100 mg, 0.32 mmol), ammonium formate (72 mg, 1.1 mmol), 10% Pd/C (34 mg, 0.03 mmol) and EtOH (10 mL) were charged and the reaction mixture was stirred at 85 °C for 2 h. The suspension was filtered through celite and the solvent was removed under vacuum to give the title compound (70 mg, yield: 99%).

HPLC-MS (Method A): Rt: 0.92 minutes; ESI+-MS m/z: 217.1 (M+1).

Step b. The title compound

A microwave tube was charged with the compound obtained in step a (75 mg, 0.35 mmol), 2-fluorobenzaldehyde (47 mg, 0.38 mmol), _NaBH3CN (65 mg, 1 mmol) and MeOH (3 mL) and the mixture was heated under microwave irradiation at 120 °C for 20 min. The reaction mixture was concentrated under reduced pressure and the residue was diluted with EtOAc and washed with aq. _saturated NaHCO3 solution. The organic layer was dried over _{anhydrous Na2SO4} , filtered and the solvent was removed in vacuo. The residue was purified by flash chromatography on silica gel, DCM:MeOH to give the title compound (41 mg, yield: 36%).

HPLC-MS (Method A): Rt, 2.06 min; ESI+-MS m/z: 325.2 [M+H] ⁺ .

This method was used to prepare Examples 64-77 using suitable starting materials.

Example 78 7-(1-Benzylpiperidin-3-yl)-2-(pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine

A Schlenk flask was charged with the compound obtained in Example 1 (125 mg, 0.33 mmol), pyrrolidine (0.05 mL, 0.67 mmol), XPhos (16 mg, 0.034 mmol), _{Pd2dba3 (} 15 mg, 0.0044 mmol), and ^KOtBu (113 mg, 1 mmol), and the flask was evacuated and backfilled with argon. Toluene (4 mL), degassed by bubbling argon for 5 min, was added, and the reaction mixture was heated at 100 °C for 16 h. The reaction mixture was concentrated under reduced pressure, and the residue was diluted with EtOAc and washed with aq. _saturated NaHCO3. The organic layer was dried over _{anhydrous Na2SO4} , filtered, and the solvent was removed in vacuo. The residue was purified by flash chromatography on silica gel, Chx:EtOAc, to give the title compound (16 mg, yield: 13%).

HPLC-MS (Method A): Rt, 2.42 minutes; ESI+-MS m/z: 362.3 [M+H] ⁺ .

This method was used to prepare Example 79 using suitable starting materials:

Example 80. N ¹ -(7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)-N ¹ -methylethane-1,2-diamine

Stage a. tert-Butyl-(2-((7-(1-benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)(methyl)amino)ethyl)carbamate

Starting from the compound obtained in Example 1 (350 mg, 0.94 mmol) and tert-butyl (2-(methylamino)ethyl)carbamate (197 mg, 1.13 mmol) and following the procedure described in Example 78, the title compound was obtained (77 mg, yield: 17%).

HPLC-MS (Method A): Rt: 2.36 min; ESI+- m/z: 465.2 (M+1).

Step b. The title compound

Starting from the compound obtained in step a (89 mg, 0.2 mmol) and following the procedure described in step d of Example 61, the title compound was obtained (72 mg, yield: 98%).

HPLC-MS (Method A): Rt, 1.68 minutes; ESI+-MS m/z: 356.3 [M+H] ⁺ .

This method was used to prepare Examples 81-83 using suitable starting materials.

Examples 84, 85, 86 and 87. (R)-1-(7-((R)-1-Benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)-N-methylpyrrolidin-3-amine, (S)-1-(7-((S)-1-benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)-N-methylpyrrolidin-3-amine, (S)-1-(7-((R)-1-benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)-N-methylpyrrolidin-3-amine and (R)-1-(7-((S)-1-benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)-N-methylpyrrolidin-3-amine

Starting from 1-(7-(1-benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)-N-methylpyrrolidin-3-amine, obtained according to a procedure similar to that described in Example 80, chiral preparative HPLC was performed [column Chiralpak IA 20 x 250 mm, 5 μm; temperature: rt; eluent: n-heptane/DCM/EtOH/Et ₂ NH 70/28/2/0.1 v/v/v/v; flow rate: 13 mL/min; Rt1: 11.9 min; Rt2: 13.2 min; Rt3: 13.7 min; Rt4: 13.9 min] to afford the title compounds.

Example 88 7-(1-Benzylpiperidin-3-yl)-3-(pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine

Step a. 7-(1-Benzylpiperidin-3-yl)-3-iodopyrazolo[1,5-a]pyrimidine

Starting from 4-iodo-1H-pyrazol-3-amine (153 mg, 0.73 mmol) and following the procedure described in step b of Example 1, the title compound (170 mg, yield: 55%) was obtained.

HPLC-MS (Method A): Rt: 2.35 minutes; ESI+-MS m/z: 419.0 (M+1).

Step b. The title compound

A microwave tube was charged with the compound obtained in step a (80 mg, 0.19 mmol), pyrrolidine (0.06 mL, 0.76 mmol), CuI (14 mg, 0.077 mmol), (S)-proline (8 mg, 0.077 mmol), K ₂ CO ₃ (53 mg, 0.38 mmol) and DMSO (2 mL) and the mixture was degassed by bubbling with argon for 5 min and heating under microwave irradiation at 100 °C for 3 h. The mixture was dissolved with EtOAc:Et ₂ O (1:1) and washed with saturated aqueous NaHCO ₃ solution. The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and the solvent was removed under vacuum. The crude product was purified by flash chromatography on silica gel, Chx:EtOAc, to give the title compound (10 mg, yield: 14%).

HPLC-MS (Method B): Rt, 2.81 minutes; ESI+-MS m/z: 362.4 [M+H] ⁺ .

Example 89 7-(1-Benzylpiperidin-3-yl)-2-methyl-3-(pyrrolidin-1-yl)pyrazolo[1,5-a]pyrimidine

Step a. 7-(1-Benzylpiperidin-3-yl)-3-iodo-2-methylpyrazolo[1,5-a]pyrimidine Starting from the compound obtained in Example 3 (415 mg, 1.35 mmol) and NIS (426 mg, 1.9 mmol) and according to the procedure described in Example 10, the title compound was obtained (434 mg, yield: 74%).

HPLC-MS (Method A): Rt: 2.46 minutes; ESI+-MS m/z: 433.1 (M+1).

Step b. The title compound

Starting from the compound obtained in step a (243 mg, 0.56 mmol) and following the procedure described in step b of Example 88, the title compound was obtained (10 mg, yield: 5%).

HPLC-MS (Method A): Rt, 1.59 minutes; ESI+-MS m/z: 406.4 [M+H] ⁺ .

Example 90 7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-amine

A solution of the compound obtained in example 8 in conc. HCl (3 mL) was stirred at 90 °C for 6 h. The reaction mixture was cooled to rt and basified with 10% aq. saturated NaHCO ₃ solution and the mixture was extracted with DCM. The combined organic layers were washed with brine, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated to dryness. The crude product was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound (43 mg, yield: 40%).

HPLC-MS (Method A): Rt, 2.94 min; ESI+-MS m/z: 320.4 [M+H] ⁺ .

Example 91 7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidine-2-carbonitrile

A Schlenk flask was charged with the compound obtained in Example 1 (90 mg, 0.24 mmol), K ₄ [Fe(CN) ₆ ]⋅2H ₂ O (24 mg, 0.06 mmol), 1,1'-bis(diphenylphosphino)ferrocene (28 mg, 0.05 mmol), Pd(OAc) ₂ (2 mg, 0.006 mmol) and Na2CO ₃ (26 mg, 0.24 mmol) and the flask was evacuated and backfilled with argon. NMP (2 mL), degassed by bubbling argon for 5 min, was added and the reaction mixture was heated at 120 °C for 16 h. The reaction mixture was diluted with EtOAc and washed with aq. saturated NaHCO ₃ solution. The organic layer was dried over anhyd. Na ₂ SO ₄ , filtered and the solvent removed in vacuo. The residue was purified by flash chromatography on silica gel, Chx:EtOAc, to give the title compound (8 mg, yield: 10%).

HPLC-MS (Method A): Rt, 2.16 min; ESI+-MS m/z: 318.2 [M+H] ⁺ .

Example 92 1-(7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)-N,N-dimethylmethanamine

Step a. 7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidine-2-carboxylic acid

Starting from 3-amino-1H-pyrazole-5-carboxylic acid (93 mg, 0.73 mmol) and following the procedure described in step b of Example 1, the title compound was obtained (94 mg, yield: 38%).

HPLC-MS (Method A): Rt: 1.19 minutes; ESI+-MS m/z: 337.2 (M+1).

Step b. 7-(1-Benzylpiperidin-3-yl)-N,N-dimethylpyrazolo[1,5-a]pyrimidine-2-carboxamide

Dimethylamine hydrochloride (170 mg, 2.1 mmol), TEA (0.58 mL, 4.1 mmol), EDC⋅HCI (398 mg, 2.1 mmol), DMAP (13 mg, 0.1 mmol) and HOBt (281 mg, 2.1 mmol) were added to a solution of the compound obtained in step a (350 mg, 0.77 mmol) in DMF (15 mL) and the reaction mixture was stirred at rt for 16 h. The mixture was dissolved with EtOAc:Et ₂ O (1:1) and washed with aq. saturated NaHCO ₃ solution. The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound (320 mg, yield: 74%).

HPLC-MS (Method A): Rt: 1.78 minutes; ESI+-MS m/z: 364.1 (M+1).

Stage c. The compound indicated in the title

A solution of the compound obtained in step b (320 mg, 0.88 mmol) in THF (4 mL) was added to a 1 M solution of AlH ₃ in THF (4.4 mL, 4.4 mmol) at 0 °C and the mixture was stirred at 0 °C for 90 min. After that, water was added dropwise and the mixture was extracted with EtOAc. The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound (30 mg, yield: 10%).

HPLC-MS (Method A): Rt, 1.80 minutes; ESI+-MS m/z: 350.2 [M+H] ⁺ .

This method was used to prepare Examples 93 and 94 using suitable starting materials.

Example 95 (7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methanol

Stage a. 7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-carbaldehyde

To a solution of the compound obtained in example 3 (50 mg, 0.16 mmol) in DMF (2 mL) was added _POCl3 (46 µL, 0.5 mmol) and the resulting mixture was stirred at rt for 16 h. The reaction mixture was cooled to 0 °C and the excess _POCl3 was quenched by adding ice. The resulting solution was neutralized using 1 M aq. NaOH, diluted with water and extracted with DCM. The organic layer was dried over _{anhydrous Na2SO4} , filtered and the solvent was removed in vacuo to give the title compound (63 mg, yield: quant.).

HPLC-MS (Method A): Rt: 2.00 minutes; ESI+-MS m/z: 335.1 (M+1).

Step b. The title compound

_NaBH4 (7 mg, 0.2 mmol) was added to a solution of the compound obtained in step a (63 mg, 0.19 mmol) in THF (4 mL) and the mixture was stirred at rt for 16 h. The reaction mixture was cooled to 0 °C and water was added slowly. The residue was extracted with DCM, the organic layer _was dried over anhydrous _Na2SO4 , filtered and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica gel, Chx:EtOAc, to give the title compound (12 mg, yield: 19%).

HPLC-MS (Method A): Rt, 1.68 minutes; ESI+-MS m/z: 337.2 [M+H] ⁺ .

Example 96 1-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-methylmethanamine

Starting from the compound obtained in step a of Example 95 (80 mg, 0.24 mmol) in 2 M methylamine in THF (0.7 ml, 1.4 mmol) and according to the procedure described in step b of Example 63, the title compound was obtained (41 mg, yield: 49%).

HPLC-MS (Method A): Rt, 1.46 min; ESI+-MS m/z: 350.1 [M+H] ⁺ .

This method was used to prepare Examples 97-99 using suitable starting materials.

Example 100 7-(1-Benzylpiperidin-3-yl)-2-methyl-3-(piperazin-1-ylmethyl)pyrazolo[1,5-a]pyrimidine

Stage a. tert-Butyl-4-((7-(1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)piperazine-1-carboxylate

Starting from the compound obtained in step a of Example 95 (100 mg, 0.3 mmol) and tert-butyl piperazine-1-carboxylate (278 mg, 1.5 mmol) and following the procedure described in step b of Example 63, the title compound was obtained (123 mg, yield: 81%).

HPLC-MS (Method A): Rt: 2.47 minutes; ESI+-MS m/z: 505.3 (M+1).

Step b. The title compound

Starting from the compound obtained in step a (123 mg, 0.24 mmol) and following the procedure described in step d of Example 61, the title compound was obtained (59 mg, yield: 60%).

HPLC-MS (Method A): Rt, 1.55 min; ESI+-MS m/z: 405.3 [M+H] ⁺ .

Example 101 3-((Benzyloxy)methyl)-7-(1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidine

NaH (60% in mineral oil) (13 mg, 0.33 mmol) was added to a solution of the compound obtained in Example 95 (45 mg, 0.13 mmol) in DMF (4 mL) and the reaction mixture was stirred at 0 °C for 30 min. Then, benzyl bromide (32 μL, 0.27 mmol) was added and the mixture was stirred for 16 h at 85 °C. The mixture was dissolved with EtOAc:Et ₂ O (1:1) and washed with brine. The organic layer was dried over anhydrous Na ₂ SO ₄ , filtered and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica gel, Chx:EtOAc, to give the title compound (22 mg, yield: 38%).

HPLC-MS (Method A): Rt, 2.53 minutes; ESI+-MS m/z: 427.2 [M+H] ⁺ .

Example 102 7-(1-Benzylpiperidin-3-yl)-2-methyl-3-(phenoxymethyl)pyrazolo[1,5-a]pyrimidine

DIAD (60 µl, 0.31 mmol) was added to a solution of the compound obtained in Example 95 (80 mg, 0.24 mmol), phenol (29 mg, 0.31 mmol) and _PPh3 (81 mg, 0.31 mmol) in toluene (10 ml) and the mixture was stirred at 100 °C for 16 h. The reaction mixture was quenched with water, diluted with EtOAc and washed with brine. The organic layer was dried over _{anhydrous Na2SO4} , filtered and the solvent was removed in vacuo. The crude product was purified by flash chromatography on silica gel, DCM:MeOH to give the title compound (21 mg, yield: 21%).

HPLC-MS (Method A): Rt, 2.18 min; ESI+-MS m/z: 413.3 [M+H] ⁺ .

Example 103 3-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)propan-1-amine

Stage a. tert-Butyl-(3-(7-(1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)allyl)carbamate

A Schlenk flask was charged with the compound obtained in Example 10 (360 mg, 0.93 mmol), tert-butyl (3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)allyl)carbamate (291 mg, 1 mmol), Pd(PPh ₃ ) ₄ (108 mg, 0.09 mmol) and Na2CO ₃ (198 mg, 1.9 mmol) and then the flask was evacuated and backfilled with argon. Toluene:EtOH:H ₂ O (3:1:1) (4 mL) was added, degassed by bubbling argon for 5 min, and the reaction mixture was heated at 80 °C for 16 h. The suspension was diluted with EtOAc and washed with aq. saturated NaHCO ₃ solution and brine. The organic layer was dried over _{anhydrous Na2SO4} , filtered and the solvent was removed in vacuo. The residue was purified by flash chromatography on silica gel, Chx:acetone, to give the title compound (56 mg, yield: 13%).

HPLC-MS (Method A): Rt: 2.46 minutes; ESI+-MS m/z: 462.2 (M+1).

Stage b. tert-Butyl-(3-(7-(1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)propyl)carbamate

Pd(OH) ₂ (27 mg, 0.2 mmol) was added to a solution of the compound obtained in step a (90 mg, 0.2 mmol) in MeOH (4 mL) and the solution was stirred under _H2 for 16 h. The suspension was filtered through celite and the solvent was removed in vacuo. The residue was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound (25 mg, yield: 28%).

HPLC-MS (Method B): Rt: 2.89 minutes; ESI+-MS m/z: 464.3 (M+1).

Stage c. The compound indicated in the title

Starting from the compound obtained in step b (25 mg, 0.05 mmol) and following the procedure described in step d of Example 61, the title compound was obtained (3 mg, yield: 11%).

HPLC-MS (Method A): Rt, 1.56 min; ESI+-MS m/z: 364.2 [M+H) ⁺ .

Examples 104 and 105. 7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-ol

Step a. (7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)boronic acid

To a solution of the compound obtained in Example 1 (50 mg, 0.13 mmol), bis(pinacolato)diboron (51 mg, 0.2 mmol) and KOAc (39 mg, 0.4 mmol) in anhydrous dioxane (5 mL) under argon was added _Pd (dppf)Fe.Cl2 (6 mg, 0.008 mmol) and the mixture was heated at 115 °C for 16 h. The reaction mixture was quenched with brine, diluted with EtOAc and washed with brine. The organic layer was dried over _{anhydrous Na2SO4} , filtered and the solvent was removed in vacuo to give the title compound (70 mg, yield: quant.).

HPLC-MS (Method C): Rt: 1.56 minutes; ESI+-MS m/z: 337.2 (M+1).

Step b. The title compound

To a solution of the compound obtained in step a (50 mg, 0.15 mmol) in AcOH (3 mL) at 0 °C was added H ₂ O ₂ (9 μL, 0.33 mmol). The solution was stirred at this temperature for 30 min and allowed to warm to rt over 16 h. The reaction mixture was filtered through celite and the solvent was removed in vacuo. The residue was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound (10 mg, yield: 22%).

HPLC-MS (Method C): Rt, 1.43 minutes; ESI+-MS m/z: 309.2 [M+H] ⁺ .

This method was also used to obtain Example 105.

Examples 106, 107, 108 and 109. (S)-2-((R)-3-(2-Methyl-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidin-1-yl)-2-phenylethanol, (S)-2-((S)-3-(2-methyl-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidin-1-yl)-2-phenylethanol, (R)-2-((S)-3-(2-methyl-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidin-1-yl)-2-phenylethanol and (R)-2-((R)-3-(2-methyl-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidin-1-yl)-2-phenylethanol

Step a. 2-Methyl-7-(piperidin-3-yl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine

Starting from the compound obtained in Example 42 (154 mg, 0.4 mmol) and following the procedure described in step a of Example 63, the title compound was obtained (120 mg, yield: quant.).

HPLC-MS (Method C): Rt: 1.12 minutes; ESI+-MS m/z: 294.1 (M+1).

Step b. 2-(3-(2-Methyl-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidin-1-yl)-2-phenylethanol

LiClO4 (79 mg, 0.75 mmol) was added to a solution of 2-phenyloxirane (45 mg, 0.37 mmol) in ACN (2 mL) and the suspension was stirred until the salts were completely dissolved. Then a solution of the compound obtained in step a (45 mg, 0.37 mmol) in ACN (0.5 mL) was added and the solution was stirred at 80 °C for 16 h. The suspension was diluted with EtOAc and washed with aq. _saturated NaHCO3 solution and brine. The organic layer was dried over _{anhydrous Na2SO4} , filtered and the solvent was removed in vacuo. The residue was purified by flash chromatography on silica gel, Chx:EtOAc, to give the title compound (34 mg, yield: 23%).

HPLC-MS (Method C): Rt: 1.95 minutes; ESI+-MS m/z: 414.3 (M+1).

Stage c. Compounds mentioned in the title

Starting from the compound obtained in step b, chiral preparative HPLC was performed [column LUX C3 21.2 × 250 mm, 5 μm; temperature: 40°C; eluent: MeOH/EtOH/NH ₃ 70/30/0.1 v/v/v; flow rate: 50 ml/min; Rt1: 2.02 min; Rt2: 2.15 min; Rt3: 2.84; Rt4: 3.83 min] to afford the title compounds.

Example 110. 2-Bromo-7-(1-(4-chlorobenzyl)piperidin-3-yl)pyrazolo[1,5-a]pyrimidine

Step a. tert-Butyl 3-acetylpiperidine-1-carboxylate

Methylmagnesium chloride (3 M in THF, 35.6 mL, 107 mmol) was added dropwise to a cooled to 0°C solution of 1-(tert-butyl)-3-ethyl piperidine-1,3-dicarboxylate (5 g, 19.43 mmol) and N,O-dimethylhydroxylamine hydrochloride (2.27 g, 23.32 mmol) in anhydrous THF (69 mL) under argon. The reaction mixture was heated to no more than rt for 16 h. The solution was then quenched with aq. saturated NH ₄ Cl at 0°C. Aq. The layer was extracted with EtOAc and the combined organic extracts were washed with brine, dried over _MgSO4 , filtered and concentrated to give the title compound as a light brown oil (4.19 g, yield: 95%).

HPLC-MS (Method E): Rt.: 3.33 min; ESI+ MS: m/z 254.0 [M+H] ⁺ .

Step b. tert-Butyl (E)-3-(3-(dimethylamino)acryloyl)piperidine-1-carboxylate

A solution of the compound obtained in step a (4.15 g, 18.28 mmol) and 1-tert-butoxy-N,N,N',N'-tetramethylmethanediamine (3.82 ml, 21.93 mmol) were mixed in a sealed reactor under argon atmosphere, and the mixture was stirred at 100 °C for 16 h. The reaction mixture was concentrated to dryness under reduced pressure to give the title compound as a brown oil (5.50 g). This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 2.63 min; ESI+ MS: m/z 283.3 [M+H] ⁺ .

Stage c. tert-Butyl-3-(2-bromopyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

To a solution of the compound obtained in step b (3.2 g, 11.33 mmol) in glacial AcOH (48 mL) was added 5-bromo-1H-pyrazol-3-amine (2.01 mg, 12.47 mmol). The reaction mixture was stirred at 50 °C for 9 h. The solvent was evaporated and the residue was purified by flash chromatography on silica gel, hexane/EtOAc as eluents, to give the title compound as a brown foam (2.85 g, yield: 66%).

HPLC-MS (Method D): Rt: 2.98 min; ESI+MS: m/z 381.1 [M+H] ⁺ .

Step d. 2-Bromo-7-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidine hydrochloride

The compound obtained in step c (1.04 g, 2.73 mmol) was treated with HCl (4 M in dioxane, 13.64 mL, 54.6 mmol). A yellow precipitate appeared immediately after the addition. The reaction mixture was stirred for 1.5 h, then the solvent was evaporated to give the title compound as a yellow solid (960 mg), which was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 2.25 min; ESI+ MS: m/z 281.0 [M+H] ⁺ .

Stage e. The title compound

To a solution of the compound obtained in step d (80 mg, 0.25 mmol) in anhydrous MeOH (2 mL) was added TEA (0.07 mL, 0.50 mmol) and the solution was stirred for 5 min. 4-Chlorobenzaldehyde (53.1 mg, 0.38 mmol) and AcOH (0.012 mL, 0.2 mmol) were added to the solution followed by sodium cyanotrihydroborate (31.7 mg, 0.50 mmol) and the reaction mixture was stirred at rt for 16 h. Then the solvent was evaporated and the reaction mixture was dissolved with DCM and poured into aq. _saturated NaHCO3 solution, the organic layer was separated and the aq. layer was extracted with DCM. The combined organic extracts were washed with brine, dried over _{anhydrous Na2SO4} and filtered. The solvent was evaporated and the residue was purified by flash chromatography on silica gel, DCM:MeOH as eluents, to give the title compound as a yellow solid (81 mg, yield: 78%).

HPLC-MS (Method D): Rt: 3.43 min; ESI+ MS: m/z 405.0 [M+H] ⁺ .

This method was used to prepare Examples 111-113 using suitable starting materials.

Examples 114 and 115. 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-(2-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidine and 3-(7-(1-(4-chlorobenzyl)piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)pyridin-2-ol

Step a. tert-Butyl 3-(2-(2-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

In a sealed tube were charged the compound obtained in step 110 (1.67 g, 4.38 mmol), (2-methoxypyridin-3-yl)boronic acid (1.00 g, 6.57 mmol), K ₂ CO ₃ (1.81 g, 13.14 mmol), Pd(PPh ₃ ) ₄ (500 mg, 0.44 mmol) and DME:H ₂ O (3:1, 26 mL). The reaction mixture was degassed with argon for 5 min and heated at 100 °C for 16 h. The suspension was diluted with EtOAc and the organic layer was separated, washed with aq. saturated Na2CO ₃ solution, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound as a brown foam (1.28 g, yield: 71%).

HPLC-MS (Method E): Rt.: 3.83 min; ESI+ MS: m/z 410.2 [M+H] ⁺ .

Step b. 2-(2-Methoxypyridin-3-yl)-7-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidine hydrochloride and 3-(7-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)pyridin-2-ol hydrochloride

Starting from the compound obtained in step a (790 mg, 1.92 mmol) and according to the procedure described in step d of Example 110, the title compounds were obtained as a 1:1 mixture (400 mg). This mixture was used in the next step without further purification.

HPLC-MS (Method D): Rt: 1.45 minutes; ESI+ MS: m/z 296.1 [M+H] ⁺ and Rt: 2.03 minutes; ESI+ MS: m/z 310.1 [M+H] ^+, respectively.

Stage c. Compounds mentioned in the title

To a solution of the mixture of compounds obtained in step b (200 mg, 0.57 mmol) in anhydrous DMA (3 mL) was added TEA (0.24 mL, 1.73 mmol) and the solution was stirred for 5 min. 1-Chloro-4-(chloromethyl)benzene (93.1 mg, 0.57 mmol) was added and the reaction mixture was stirred at 70 °C for 16 h. The reaction mixture was cooled to rt and poured into aq. saturated NaHCO ₃ solution and DCM, the organic layer was separated and the aq. layer was extracted with DCM. The combined organic extracts were washed with brine, dried over anhydrous Na ₂ SO ₄ and filtered. The solvent was evaporated and the residue was purified by flash chromatography on silica gel, DCM:MeOH as eluents, to give the title compounds as yellow solids (69 mg, yield: 26%, and 52 mg, yield: 20%, respectively).

HPLC-MS (Method D): Rt.: 3.60 min; ESI+ MS: m/z 434.1 [M+H] ⁺ and Rt: 2.73 min; ESI+ MS: m/z 420.1 [M+H] ^+, respectively.

This method was used to prepare Examples 116-119 using suitable starting materials.

Example 120. 1-(2-Bromo-7-(1-(4-chlorobenzyl)piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine

Step a. 2-Bromo-7-(1-(4-chlorobenzyl)piperidin-3-yl)pyrazolo[1,5-a]pyrimidine-3-carbaldehyde

To a solution of the compound obtained in example 110 (175 mg, 0.43 mmol) in DMF (1.1 mL) was added _POCl3 (0.11 mL, 1.19 mmol) and the reaction mixture was stirred at rt for 16 h. After that, the reaction mixture was cooled to 0 °C and ice water was carefully added, the mixture was basified with 2 N NaOH to pH 11. The resulting suspension was extracted with EtOAc. The combined organic extracts were washed with brine, dried over _{anhydrous Na2SO4} , filtered and concentrated to give the title compound as a brown solid (175 mg, yield: 75%).

HPLC-MS (Method E): Rt.: 3.82 min; ESI+ MS: m/z 433.0 [M+H] ⁺ .

Step b. The title compound

Starting from the compound obtained in step a (175 mg, 0.40 mmol) and (tetrahydro-2H-pyran-4-yl)methanamine (116 mg, 1.0 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (60 mg, yield: 27%).

HPLC-MS (Method E): Rt.: 4.02 min; ESI+ MS: m/z 532.1 [M+H] ⁺ .

Example 121. 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine

Step a. tert-Butyl 3-(3-bromo-2-methylpyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

Starting with the compound obtained in step b of Example 110 (2 g, 7.08 mmol) and 4-bromo-5-methyl-1H-pyrazol-3-amine (1.37 g, 7.79 mmol) and following the procedure described in step c of Example 110, the title compound was obtained as a brown foam (2.04 g, yield: 73%).

HPLC-MS (Method E): Rt.: 3.75 min; ESI+ MS: m/z 395.1 [M+H] ⁺ .

Step b. tert-Butyl 3-(2-methyl-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

Starting from the compound obtained in step a (1.2 g, 3.04 mmol) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.93 g, 4.55 mmol) and following the procedure described in step a of Examples 114 and 115, the title compound was obtained as a brown solid (1.78 g, yield: 58%).

HPLC-MS (Method E): Rt.: 3.37 min; ESI+ MS: m/z 394.2 [M+H] ⁺ .

Step c. 2-Methyl-7-(piperidin-3-yl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine dihydrochloride

Starting from the compound obtained in step b (0.70 g, 1.78 mmol) and following the procedure described in step d of Example 110, the title compound was obtained as a yellow solid (650 mg).

HPLC-MS (Method E): Rt.: 2.17 min; ESI+ MS: m/z 294.1 [M+H] ⁺ .

Stage d. Title compound

Starting from the compound obtained in step c (80 mg, 0.21 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (61.8 mg, yield: 65%).

HPLC-MS (Method D): Rt: 3.30 min; ESI+ MS: m/z 418.1 [M+H] ⁺ .

This method was used to prepare examples 122-133 using suitable starting materials.

Example 134. (4-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)pyridin-2-yl)methanol

Step a. 4-Bromo-2-(((tert-butyldimethylsilyl)oxy)methyl)pyridine

To a stirred solution of (4-bromopyridin-2-yl)methanol (400 mg, 2.13 mmol) in DMF (8 mL) were added imidazole (290 mg, 4.25 mmol) and tert-butyldimethylchlorosilane (321 mg, 2.13 mmol). The reaction mixture was stirred at rt for 16 h. The mixture was then diluted with EtOAc and the organic layer was washed with water and brine, dried over _{anhydrous Na2SO4} , filtered and concentrated in vacuo. The residue was purified by flash chromatography on silica gel, hexane:EtOAc, to give the title compound as a brown foam (514 mg, yield: 80%).

HPLC-MS (Method E): Rt.: 3.15 min; ESI+ MS: m/z 302.0 [M+H] ⁺ .

Step b. 2-(((tert-Butyldimethylsilyl)oxy)methyl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine

To a solution of the compound obtained in step a (514 mg, 1.7 mmol) in dioxane (10 mL) were added 4,4,4',4',5,5,5',5'-octamethyl-2,2'-bis(1,3,2-dioxaborolane) (518 mg, 2.04 mmol), _PdCl2 (dppf) _-CH2Cl2 adduct (139 mg, 0.17 mmol) and potassium acetate (501 mg, 5.10 mmol). The reaction mixture was degassed with argon for 5 min and heated at 100 _° C for 16 h. The reaction mixture was then filtered through double-cell filter paper and the black solid on the filter was washed with EtOAc. The filtrate was concentrated in vacuo and the residue was triturated and sonicated in hexane for 30 min. The black suspension was filtered again over a double filter paper and the black solid on the filter was washed with hexane. The filtrate was concentrated to give 830 mg of a brown oil, which was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 3.23 min; ESI+ MS: m/z 268 [M+H] ⁺ .

Stage c. tert-Butyl-3-(3-(2-(((tert-butyldimethylsilyl)oxy)methyl)pyridin-4-yl)-2-methylpyrazolo[1,5-a]pyrimidin-7-yl)piperidin-1-carboxylate

Starting from the compound obtained in step b (200 mg, 0.5 mmol) and following the procedure described in step a of Example 114, the title compound was obtained (125 mg, yield: 46%).

HPLC-MS (Method E): Rt.: 4.78 min; ESI+ MS: m/z 539.1 [M+H] ⁺ .

Step d. (4-(2-Methyl-7-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)pyridin-2-yl)methanol dihydrochloride

Starting from the compound obtained in step c (110 mg, 0.20 mmol) and following the procedure described in step d of Example 110, the title compound was obtained (76 mg, yield: 94%) after evaporation of the solvent, trituration and sonication of the solid in hexane, filtration and drying under vacuum.

HPLC-MS (Method E): Rt.: 2.13 min; ESI+ MS: m/z 324.1 [M+H] ⁺ .

Stage e. The title compound

Starting from the compound obtained in step d (75 mg, 0.18 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (28 mg, yield: 32%).

HPLC-MS (Method E): Rt.: 3.53 min; ESI+ MS: m/z 448.1 [M+H] ⁺ .

This method was used to prepare Example 135 using suitable starting materials:

This method (steps b-e) was used to prepare examples 136-138 using suitable starting materials.

Example 139. 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrimidine

Step a. tert-Butyl 3-(3-acetyl-2-methylpyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

To a solution of the compound obtained in step a of Example 121 (1 g, 2.53 mmol) in toluene (3 mL) were added tributyl(1-ethoxyvinyl)stannane (1.70 mL, 5.06 mmol) and bis(triphenylphosphine)palladium(II) chloride (178 mg, 0.253 mmol). The reaction mixture was heated at 80 °C for 24 h. Afterwards, the solvent was evaporated and the residue was purified by flash chromatography on silica gel, hexane:EtOAc, to give the title compound as a brown foam (721 mg, yield: 80%).

HPLC-MS (Method E): Rt.: 3.43 min; ESI+ MS: m/z 359.2 [M+H] ⁺ .

Step b. tert-Butyl(E)-3-(3-(3-(dimethylamino)acryloyl)-2-methylpyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

The compound obtained in step a (721 mg, 2.01 mmol) and 1-tert-butoxy-N,N,N',N'-tetramethylmethanediamine (2 ml, 9.69 mmol) were stirred at 100 °C in a sealed reactor under argon atmosphere for 3 h. The reaction mixture was concentrated to dryness under reduced pressure to give the title compound as a brown oil (832 mg, yield: quant.).

HPLC-MS (Method E): Rt.: 3.00 min; ESI+ MS: m/z 414.2 [M+H] ⁺ .

Step c. tert-Butyl 3-(2-methyl-3-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

The compound obtained in step b (397 mg, 0.96 mmol) and formimidamide acetate (198 mg, 1.92 mmol) were stirred at 130 °C in a sealed reactor under argon for 2 h. After that, the reaction mixture was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound as a brown foam (100 mg, yield: 26%).

HPLC-MS (Method E): Rt.: 3.55 min; ESI+ MS: m/z 395.2 [M+H] ⁺ .

Step d. 2-Methyl-7-(piperidin-3-yl)-3-(pyrimidin-4-yl)pyrazolo[1,5-a]pyrimidine hydrochloride

Starting with the compound obtained in step c (100 mg, 0.25 mmol) and following the procedure described in step d of Example 110, the title compound was obtained (93 mg). This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 2.28 min; ESI+ MS: m/z 295.1 [M+H] ⁺ .

Stage e. The title compound

Starting from the compound obtained in step d (93 mg, 0.25 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (39 mg, yield: 33%).

HPLC-MS (Method E): Rt.: 4.22 min; ESI+MS: m/z 419.1 [M+H] ⁺ .

This method was used to prepare Example 140 using the appropriate starting materials:

Example 141 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-N,N,2-trimethylpyrazolo[1,5-a]pyrimidin-3-amine

Step a. N-(5-Methyl-1H-pyrazol-3-yl)acetamide

5-Methyl-1H-pyrazol-3-amine (2.69 g, 27.7 mmol) was dissolved in water (24 ml) followed by slow addition of sodium bicarbonate (6.98 g, 83.0 mmol) to which acetic anhydride (5 ml, 53.0 mmol) was added dropwise. The reaction mixture was heated under reflux for 16 h. The suspension was cooled, filtered and the resulting solid was washed with water. The final compound was found to be partially soluble in water, the aqueous phase was also concentrated and both solids were combined and dried in vacuo to give the title compound (1.89 g, yield: 49%).

HPLC-MS (Method E): Rt.: 1.10 min; ESI+ MS: m/z 140.0 [M+H] ⁺ .

Step b. N-(5-Methyl-4-nitro-1H-pyrazol-3-yl)acetamide

Sulfuric acid (9.7 mL, 180 mmol) was cooled to 0 °C and the compound obtained in step a (1.0 g, 7.19 mmol) was slowly added. Then nitric acid (0.48 mL, 10.78 mmol) was added dropwise. The reaction mixture was stirred at 0 °C for 30 min. The solution was poured onto ice and a solid precipitated. The solid was filtered through a sintered glass funnel and dried under vacuum to give the title compound (1.89 g, yield: 49%).

HPLC-MS (Method E): Rt.: 1.42 min; ESI+ MS: m/z 185.0 [M+H] ⁺ .

Stage c. 5-Methyl-4-nitro-1H-pyrazol-3-amine hydrochloride

The compound obtained in step b (1.03 g, 5.59 mmol) and 6 M HCl (6 mL, 36 mmol) were heated at 100 °C for 2 h. Then, the solvent was evaporated to give the title compound (793 mg). This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 1.38 min; ESI+ MS: m/z 143.1 [M+H] ⁺ .

Stage d. tert-Butyl-3-(2-methyl-3-nitropyrazolo[1,5-d]pyrimidin-7-yl)piperidine-1-carboxylate

Starting from the compound obtained in step c (793 mg, 5.59 mmol) and following the procedure described in step c of Example 110, the title compound was obtained (1.89 g, yield: 94%).

HPLC-MS (Method E): Rt.: 3.23 min; ESI+ MS: m/z 362.1 [M+H] ⁺ .

Step E. tert-Butyl-3-(3-amino-2-methylpyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

To a solution of the compound obtained in step d (1.89 g, 5.23 mmol) in EtOH (31 mL) was added zinc (10.26 g, 157 mmol) and calcium chloride (0.29 g, 2.61 mmol) dissolved in a minimum amount of water. The reaction mixture was heated under reflux for 2 h. After this time, the suspension was filtered through a pad of celite and the solid was washed with hot EtOH. The filtrate was concentrated and the residue was purified by flash chromatography on silica gel, EtOAc:MeOH:NH ₃ , to give the title compound (864 mg, yield: 50%).

HPLC-MS (Method E): Rt.: 2.65 min; ESI+ MS: m/z 332.2 [M+H] ⁺ .

Step f. tert-Butyl 3-(3-(dimethylamino)-2-methylpyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

Starting from the compound obtained in step e (576 mg, 1.74 mmol) and 37% aqueous formaldehyde (0.39 ml, 5.21 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (1.89 g, yield: 94%).

HPLC-MS (Method E): Rt.: 3.35 min; ESI+ MS: m/z 360.2 [M+H] ⁺ .

Step g. N,N,2-Trimethyl-7-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-amine hydrochloride

Starting from the compound obtained in step f (674 mg, 1.87 mmol) and following the procedure described in step d of Example 110, the title compound was obtained (623 mg). This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 1.83 min; ESI+ MS: m/z 260.1 [M+H] ⁺ .

Stage h. Title compound

Starting from the compound obtained in step g (242 mg, 0.93 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (225 mg, yield: 62%).

HPLC-MS (Method E): Rt.: 3.97 min; ESI+ MS: m/z 384.1 [M+H] ⁺ .

This method was used to prepare Example 142 using the appropriate starting materials:

Example 143 N-Benzyl-7-(1-benzylpiperidin-3-yl)-N,2-dimethylpyrazolo[1,5-a]pyrimidin-3-amine

Step a. tert-Butyl 3-(3-((tert-butoxycarbonyl)amino)-2-methylpyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

To a solution of the compound obtained in step e of Example 141 (288 mg, 0.86 mmol) in DCM (5 mL) were added TEA (0.18 mL, 1.30 mmol) and _Boc2O (284 mg, 1.30 mmol) and the reaction mixture was stirred at rt for 16 h. The resulting mixture was diluted with saturated aqueous _NaHCO3 . The organic layer was separated and washed with brine, dried over _{anhydrous Na2SO4} , filtered and concentrated to give the title compound (375 mg).

HPLC-MS (Method E): Rt.: 3.47 min; ESI+ MS: m/z 432.2 [M+H] ⁺ .

Step b. tert-Butyl 3-(3-((tert-butoxycarbonyl)(methyl)amino)-2-methylpyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

To a cooled to 0 °C solution of the title compound (a) (390 mg, 0.90 mmol) in DMF (3 mL) was added sodium hydride (60 wt % in mineral oil, 54 mg, 1.35 mmol) under argon and the resulting mixture was stirred for 20 min. Following the addition of iodomethane (0.11 mL, 1.80 mmol), the reaction mixture was stirred at rt for 2 h. After this time, starting material still remained and more reagents were added at 0 °C and the reaction mixture was stirred at rt for 16 h. The reaction mixture was then concentrated in vacuo and the residue was triturated with EtOAc and aq. saturated NaHCO ₃ solution. The organic layer was separated and washed with brine, dried over anhyd. Na ₂ SO ₄ , filtered and concentrated to give the title compound (330 mg).

HPLC-MS (Method E): Rt.: 3.73 min; ESI+ MS: m/z 446.2 [M+H] ⁺ .

Step c. N,2-Dimethyl-7-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-amine hydrochloride

Starting from the compound obtained in step b (330 mg, 0.74 mmol) and following the procedure described in step d of Example 110, the title compound (623 mg) was obtained.

HPLC-MS (Method E): Rt.: 1.85 min; ESI+ MS: m/z 246.1 [M+H] ⁺ .

Step d. Title compound

Starting from the compound obtained in step c (236 mg, 0.74 mmol) and benzaldehyde (0.22 ml, 2.22 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (24 mg, yield: 7%).

HPLC-MS (Method E): Rt.: 4.45 min; ESI+ MS: m/z 426.2 [M+H] ⁺ .

Example 144 N-Benzyl-1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methanamine

Step a. tert-Butyl 3-(2-methylpyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

Starting from the compound obtained in step b of Example 110 (2.0 g, 7.08 mmol) and 5-methyl-1H-pyrazol-3-amine (0.75 g, 7.79 mmol) and according to the procedure described in step c of Example 110, the title compound was obtained (2.1 g, yield: 93%).

HPLC-MS (Method E): Rt.: 3.22 min; ESI+ MS: m/z 317.1 [M+H] ⁺ .

Step b. 2-Methyl-7-(piperidin-3-yl)pyrazolo[1,5-a]pyrimidine hydrochloride

Starting from the compound obtained in step a (600 mg, 1.89 mmol) and following the procedure described in step d of Example 110, the title compound was obtained (403 mg). This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 1.98 min; ESI+ MS: m/z 217.1 [M+H] ⁺ .

Stage c. 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidine

Starting from the compound obtained in step b (403 mg, 1.60 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (379 mg, yield: 68%).

HPLC-MS (Method E): Rt.: 3.78 min; ESI+ MS: m/z 341.1 [M+H] ⁺ .

Step d. 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde

Starting from the compound obtained in step c (409 mg, 1.09 mmol) and following the procedure described in step a of Example 120, the title compound was obtained (379 mg, yield: 98%).

HPLC-MS (Method E): Rt.: 3.72 min; ESI+ MS: m/z 389.1 [M+H] ⁺ .

Stage e. The title compound

Starting from the compound obtained in step d (200 mg, 0.54 mmol) and phenylmethanamine (0.17 ml, 1.62 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (63 mg, yield: 25%).

HPLC-MS (Method E): Rt.: 4.23 min; ESI+ MS: m/z 460.2 [M+H] ⁺ .

This method was used to prepare Examples 145-192 using suitable starting materials.

Examples 193 and 194. (S)-1-(4-((((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one and (R)-1-(4-((((7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one

Starting from 1-(4-((((7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one, obtained according to a procedure similar to that described in Example 144, chiral preparative HPLC was performed [column Chiralpak AD-H 20 x 250 mm, 5 μm; temperature: rt; eluent: g-heptane/EtOH/Et ₂ NH 70/30/0.1 v/v/v, flow rate 14 ml/min; Rt1: 21.1 min; Rt2: 24.0 min] to give the title compounds.

Examples 195, 196, 197 and 198. (R)-N-((7-((R)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-1-phenylethan-1-amine, (R)-N-((7-((S)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-1-phenylethan-1-amine, (S)-N-((7-((R)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-1-phenylethan-1-amine and (S)-N-((7-((S)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-1-phenylethan-1-amine

Starting from N-((7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-1-phenylethanamine, obtained according to a procedure similar to that described in Example 144, chiral preparative HPLC was performed twice [column Chiralpak AD-H, 20 x 250 mm, 5 μm; temperature: rt; eluent: n-heptane/EtOH/Et ₂ NH 95/5/0.02 v/v/v; flow rate: 20 mL/min; Rt1: 6.9 min: Rt2: 8.2 min, and column Chiralpak AD-H, 20 x 250 mm, 5 μm; temperature: rt; eluent: n-heptane/EtOH/Et ₂ NH 90/10/0.03 v/v/v; flow rate: 20 ml/min; Rt1: 7.2 min: Rt2: 9.3 min] to give the title compounds.

Examples 199 and 200. (S)-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine and (R)-1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine

Starting from 1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine, obtained according to a procedure similar to that described in Example 144, chiral preparative HPLC was performed [column Reprosil AMS, 20 x 250 mm, 5 μm; temperature: 40°C; eluent: MeOH/CO ₂ /NH ₃ 20/80/0.2 v/v/v/; flow rate: 50 ml/min; Rt1: 3.19; Rt2: 3.65] to give the title compounds.

Examples 201, 202 and 203. (+/-)-1-(7-((R/S)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-(((S/R)-tetrahydrofuran-3-yl)methyl)methanamine, 1-(7-((R)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-(((R)-tetrahydrofuran-3-yl)methyl)methanamine and 1-(7-((S)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-(((15)-tetrahydrofuran-3-yl)methyl)methanamine

Starting from 1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydrofuran-3-yl)methyl)methanamine, obtained according to a procedure similar to that described in Example 144, chiral preparative HPLC was performed [column LUX C3, 21.1 x 250 mm, 5 μm; temperature: rt; eluent: ACN/NH ₃ 100/0.2 v/v; flow rate: 13 ml/min; Rt1: 3.9 min; Rt2: 4.65 min; Rt3: 5.38 min] to give the title compounds.

Examples 204 and 205. (S)-1-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine and (R)-1-(7-(1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine

Starting from 1-(7-(1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine, obtained according to a procedure similar to that described in Example 144, chiral preparative HPLC was performed [column Chiralpak AD-H, 20 x 250 mm, 5 μm; temperature: rt; eluent: H-heptane/EtOH/Et ₂ NH 85/15/0.05 v/v/v; flow rate: 12 ml/min; Rt1: 11.7; Rt2: 13.8 min] to afford the title compounds.

Examples 206 and 207. (S)-1-(7-(1-(4-Fluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine and (R)-1-(7-(1-(4-fluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine

Starting from 1-(7-(1-(4-fluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine, obtained according to a procedure similar to that described in Example 144, chiral preparative HPLC was performed [column Chiralpak AD-H, 20 x 250 mm, 5 μm; temperature: rt; eluent: H-heptane/EtOH/Et ₂ NH 95/5/0.4 v/v/v; flow rate: 14 ml/min; Rt1: 32.5 min; Rt2: 36.1 min] to afford the title compounds.

Examples 208 and 209. (S)-3-((3-(2-Methyl-3-((((tetrahydro-2H-pyran-4-yl)methyl)amino)methyl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidin-1-yl)methyl)benzonitrile and (R)-3-((3-(2-methyl-3-((((tetrahydro-2H-pyran-4-yl)methyl)amino)methyl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidin-1-yl)methyl)benzonitrile

Starting from 3-((3-(2-methyl-3-((((tetrahydro-2H-pyran-4-yl)methyl)amino)methyl)pyrazolo[1,5-a]pyrimidin-7-yl)piperidin-1-yl)methyl)benzonitrile, obtained according to a procedure similar to that described in Example 144, chiral preparative HPLC was performed [column Chiralpak AD-H, 20 x 250 mm, 5 μm: temperature: rt; eluent: H-heptane/EtOH/Et ₂ NH 70/30/0.1, v/v/v; flow rate: 12 ml/min; Rt1: 15.1 min; Rt2: 17.6 min] to give the title compounds.

Examples 210 and 211. (S)-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-dimethylmethanamine and (R)-1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-dimethylmethanamine

Starting from 1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-dimethylmethanamine, obtained according to a procedure similar to that described in Example 144, chiral preparative HPLC was performed [column Chiralcel OJ, 20 x 250 mm; 5 μm; temperature: rt; eluent: H-heptane/EtOH/Et ₂ NH 90/10/0.03 v/v/v; flow rate: 15 ml/min; Rt1: 6.1 min; Rt2: 7.5 min] to afford the title compounds.

Examples 212 and 213. (R)-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-methylmethanamine and (S)-1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-methylmethanamine

Starting from 1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-methylmethanamine, obtained according to a procedure similar to that described in Example 144, chiral preparative HPLC was performed [column LUX C3, 21.2 X 250, 5 μm; temperature: rt; eluent MeOH/NH ₃ 100/0.2 v/v; flow rate: 21 ml/min; Rt1: 2.7 min; Rt2: 2.98 min] to afford the title compounds.

Examples 214 and 215. ((S)-1-(7-(1-Benzylpiperidin-3-yl)-2-chloropyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine and ((-R)-1-(7-(1-benzylpiperidin-3-yl)-2-chloropyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine

Starting from 1-(7-(1-benzylpiperidin-3-yl)-2-chloropyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine, obtained according to a procedure similar to that described in Example 144, chiral preparative HPLC was performed [column Chiralpak AD-H, 20 x 250 mm; 5 μm; temperature: rt; eluent H-heptane/EtOH/Et ₂ NH 80/20/0.1 v/v/v; flow rate: 11 ml/min; Rt1: 13.23 min; Rt2: 16.2 min] to afford the title compounds.

Examples 216 and 217. (S)-1-(4-((((7-(1-Benzylpiperidin-3-yl)-2-chloropyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one and (R)-1-(4-((((7-(1-benzylpiperidin-3-yl)-2-chloropyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one

Starting from 1-(4-((((7-(1-benzylpiperidin-3-yl)-2-chloropyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethanone, obtained according to a procedure similar to that described in Example 144, chiral preparative HPLC was performed [column Chiralpak AD-H, 20 x 250 mm; 5 μm; temperature: rt; eluent H-heptane/EtOH/Et ₂ NH 80/20/0.1 v/v/v; flow rate: 12 ml/min; Rt1: 15.8 min; Rt2: 18.4 min] to give the title compounds.

Example 218. 4-((((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidine-1-carboxamide

Stage a. tert-Butyl-((1-(tosylcarbamoyl)piperidin-4-yl)methyl)carbamate

To a cooled to 0 °C solution of tert-butyl (piperidin-4-ylmethyl)carbamate (500 mg, 2.33 mmol) in anhydrous DCM (16 mL) was added 4-methylbenzenesulfonyl isocyanate (0.5 mL, 3.29 mmol) dropwise under argon. The reaction mixture was allowed to reach rt and stirred for 16 h. The reaction mixture was then quenched with sodium acetate/AcOH buffer pH 5 and brine. The aqueous layer was extracted with DCM and the combined organic extracts were dried over MgSO ₄ , filtered and concentrated. The residue was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound as an oil (461 mg, yield: 48%).

HPLC-MS (Method E): Rt.: 2.05 min; ESI+ MS: m/z 410.1 [M+H] ⁺ .

Step b. tert-Butyl ((1-carbamoylpiperidin-4-yl)methyl)carbamate

Sodium (155 mg, 6.74 mmol) and naphthalene (860 mg, 6.71 mmol) in anhydrous THF (67 mL) were stirred under argon for 2 h to give a dark green solution, then the solution was cooled to -78 °C and the title compound (460 mg, 1.18 mmol) in anhydrous THF (22 mL) was added dropwise (30 min addition). The reaction mixture was stirred at -78 °C for 1.5 h and then allowed to reach rt and stirred for an additional 1.5 h at this temperature. The reaction mixture was then cooled to -78 °C and carefully quenched with MeOH. The solution was then allowed to reach rt and the solvent was evaporated. The residue was partitioned between DCM and aq. saturated NaHCO ₃ and aq. The layer was extracted with DCM. The combined organic extracts were dried over _MgSO4 , filtered and concentrated. The residue was purified by flash chromatography on silica gel, DCM:MeOH, to give the title compound as an oil (150 mg, yield: 52%).

HPLC-MS (Method E): Rt.: 2.10 min; ESI+ MS: m/z 258.1 [M+H] ⁺ .

Stage C. 4-(Aminomethyl)piperidine-1-carboxamide hydrochloride

Starting from the compound obtained in step b (150 mg, 0.58 mmol) and following the procedure described in step d of Example 110, the title compound (113 mg) was obtained.

HPLC-MS (Method E): Rt.: 0.92 min; ESI+ MS: m/z 158.1 [M+H] ⁺ .

Stage d. Title compound

Starting from the compound obtained in step c (113 mg, 0.58 mmol) and the compound obtained in step d of Example 144 (128 mg, 0.35 mmol), and according to the procedure described in step e of Example 110, the title compound was obtained (14 mg, yield: 8%).

HPLC-MS (Method E): Rt.: 3.82 min; ESI+ MS: m/z 510.2 [M+H] ⁺ .

Example 219. (7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methanamine

Step a. N-((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)prop-2-en-1-amine

Starting from the compound obtained in step d of Example 144 (1.08 g, 2.93 mmol) and prop-2-en-1-amine (0.44 ml, 5.86 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (863 mg, yield: 71%).

HPLC-MS (Method E): Rt.: 4.20 min; ESI+ MS: m/z 410.2 [M+H] ⁺ .

Step b. The title compound

To a solution of the compound obtained in step a (863 mg, 2.10 mmol) in anhydrous DCM (50 mL) were added Pd(OAc) ₂ (47 mg, 0.20 mmol), _PPh3 (165 mg, 0.62 mmol) and 1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione (888 mg, 5.69 mmol). The resulting mixture was stirred at rt under argon for 16 h. Then the reaction mixture was quenched with aq. _saturated NaHCO3 solution and the aq. layer was extracted with DCM. The combined organic extracts were dried over _MgSO4 , filtered and evaporated. The residue was purified by flash chromatography on silica gel, DCM:MeOH:NH ₃ , to give the title compound as a solid (517 mg, yield: 63%).

HPLC-MS (Method E): Rt.: 4.43 min; ESI+ MS: m/z 370.1 [M+H] ⁺ .

Example 220. 1-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-(((2R,6S)-2,6-dimethyltetrahydro-2H-pyran-4-yl)methyl)methanamine

Step a. (2R,6S)-4-(Methoxymethylene)-2,6-dimethyltetrahydro-2H-pyran

To a cooled to 0 °C solution of LDA (2 M in THF, 4.4 mL, 8.80 mmol) was added a solution of (methoxymethyl)diphenylphosphine oxide (1.92 g, 7.80 mmol) in anhydrous THF (30 mL). The resulting red solution was cooled to -40 °C and another solution of (2R,6S)-1,6-dimethyltetrahydro-4H-pyran-4-one (250 mg, 1.95 mmol) in anhydrous THF (10 mL) was added. The resulting brown suspension was stirred at -40 °C for 30 min and then heated to <40 °C for 16 h under argon. The reaction mixture was then cooled to rt and quenched with water. Brine was then added to this solution and the aqueous layer was extracted with EtOAc. The combined organic extracts were dried over _MgSO4 , filtered and concentrated. The residue was purified by flash chromatography on silica gel, hexane/EtOAc, to give the title compound as an oil (141 mg, yield: 46%).

Step b. (2R,6S)-2,6-Dimethyltetrahydro-2H-pyran-4-carbaldehyde

To a solution of the compound obtained in step a (140 mg, 0.89 mmol) in ACN (1 mL) was added 2 M HCl (1.4 mL, 2.80 mmol). The mixture was stirred at rt for 5 h. The reaction mixture was diluted with 2 M HCl and the aq. layer was extracted with DCM. The combined organic extracts were dried over MgSO ₄ , filtered and concentrated at low pressure and low temperature to avoid distillation of the product, since it apparently had a low boiling point.

This afforded the title compound (120 mg), which was used in the next step without further purification.

Stage c. The compound indicated in the title

Starting from the compound obtained in step b (43 mg, 0.3 mmol) and (7-(1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methanamine (prepared according to the procedure described in Example 219) (150 mg, 0.44 mmol) and according to the procedure described in step e of Example 110, the title compound was obtained (118 mg, yield: 85%).

HPLC-MS (Method E): Rt.: 4.50 min; ESI+ MS: m/z 462.3 [M+H] ⁺ .

Examples 221, 222 and 223. (+/-)-1-(7-((R/S)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-(((R/S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)methanamine, (1-(7-((R)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-(((S)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)methanamine and (1-(7-((S)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-(((R)-2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)methanamine

Starting from 1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((2,2-dimethyltetrahydro-2H-pyran-4-yl)methyl)methanamine, obtained according to a procedure similar to that described in Example 220, chiral preparative HPLC was performed [column LUX A1, 21.2 x 250 mm; 5 μm; temperature: rt; eluent n-heptane/iPrOH/NH ₃ 80/20/0.5 v/v/v; flow rate: 21 ml/min; Rt1: 5.64 min; Rt2: 6.35; Rt3: 7.37 min] to give the title compounds.

Examples 224, 225 and 226. (+/-)-(R/S)-N-((7-((R/S)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-1-(tetrahydro-2H-pyran-4-yl)ethan-1-amine, (S)-N-((7-((R)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-1-(tetrahydro-2H-pyran-4-yl)ethan-1-amine and (R)-N-((7-((S)-1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-1-(tetrahydro-2H-pyran-4-yl)ethan-1-amine

Starting from N-((7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-1-(tetrahydro-2H-pyran-4-yl)ethanamine, obtained according to a procedure similar to that described in Example 220, chiral preparative HPLC was performed [column LUX C4, 21.2 x 250 mm; 5 μm; temperature: rt; eluent ACN/Et ₂ NH 100/1 v/v; flow rate: 21 ml/min; Rt1: 7.58 min; Rt2: 8.39; Rt3: 12.03 min] to give the title compounds.

Examples 227 and 228. (R)-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-(cyclopropylmethyl)-N-methylmethanamine and (S)-1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-(cyclopropylmethyl)-N-methylmethanamine

Step a. 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-(cyclopropylmethyl)-N-methylmethanamine

Starting from the compound obtained in Example 157 (685 mg, 1.6 mmol) and paraformaldehyde (976 mg, 32.5 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (314 mg, yield: 43%).

HPLC-MS (Method E): Rt.: 5.15 min; ESI+ MS: m/z 438.0 [M+H] ⁺ .

Step b. Title compounds

Starting from the compound obtained in step a, chiral preparative HPLC was performed [column Chiralcel OJ, 20 x 250 mm; 5 μm; temperature: rt; eluent H-heptane/EtOH/Et ₂ NH 98/2/0.01 v/v/v; flow rate: 19 ml/min; Rt1: 7.6 min; Rt2: 11.1 min] to afford the title compounds.

This method (step a) was used to prepare examples 229-234 using suitable starting materials:

Example 235. N-((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-2,2,2-trifluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)ethan-1-amine

To a solution of 1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine (prepared according to the procedure described in Example 144) (60 mg, 0.12 mmol) in DCM (4 mL) were added TEA (0.04 mL, 0.28 mmol) and 2,2,2-trifluoroethyl trifluoromethanesulfonate (0.14 mL, 1.0 mmol) and the reaction mixture was stirred under argon at rt for 4 days. The reaction mixture was poured into water and the aqueous layer was extracted with DCM. The combined organic extracts were dried over _MgSO4 , filtered and concentrated to give the title compound as an oil (58.6 mg, yield: 74%).

HPLC-MS (Method E): Rt.: 4.52 min; ESI+ MS: m/z 550.2 [M+H] ⁺ .

Example 236. 2-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-dimethylethan-1-amine

Step a. (E)-7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-(2-nitrovinyl)pyrazolo[1,5-a]pyrimidine

To a solution of the compound obtained in step d of Example 144 (500 mg, 1.35 mmol) in MeOH (10 mL) were added potassium acetate (532 mg, 5.42 mmol), methylamine hydrochloride (252 mg, 3.73 mmol) and nitromethane (0.08 mL, 1.49 mmol). The reaction mixture was stirred under argon atmosphere at rt for 60 h. Then it was poured into water and the solid precipitated. The solid was filtered, washed with water and dried under vacuum to give the title compound as a yellow solid (392 mg, yield: 70%). This solid was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 4.40 min; ESI+ MS: m/z 412.2 [M+H] ⁺ .

Step b. 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-(2-nitroethyl)pyrazolo[1,5-a]pyrimidine

To a solution of the compound obtained in step a (343 mg, 0.83 mmol) in MeOH (10 mL) was added sodium borohydride (98 mg, 2.58 mmol) slowly portionwise into the solution at rt. The reaction mixture was stirred under nitrogen for 45 min. The solvent was evaporated and the residue was diluted with a mixture of EtOAc, aq. _NaHCO3 and brine. The aq. layer was extracted with EtOAc, the combined organic extracts were dried over _MgSO4 , filtered and concentrated to give the title compound as a solid (328 mg, yield: 95%). This solid was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 3.93 min; ESI+ MS: m/z 414.2 [M+H] ⁺ .

Stage c. 2-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)ethan-1-amine

To a solution of the compound obtained in step b (328 mg, 0.79 mmol) in MeOH (10 mL) was added Raney nickel (46.5 mg, 0.79 mmol) and the reaction mixture was stirred under hydrogen atmosphere at 40 °C for 16 h. It was then filtered through a pad of celite and the solvent was evaporated to give the title compound as an oil (298 mg, yield: 98%). This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 5.06 min; ESI+ MS: m/z 384.1 [M+H] ⁺ .

Step d. Title compound

Starting from the compound obtained in step c (135 mg, 0.35 mmol) and following the procedure described in Examples 227 and 228, the title compound was obtained (72 mg, yield: 49%).

HPLC-MS (Method E): Rt.: 4.27 min; ESI+ MS: m/z 412.2 [M+H] ⁺ .

Example 237. 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2,6-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine

Stage a. tert-Butyl-3-propionylpiperidine-1-carboxylate

To a stirred solution of 1-(tert-butyl)-3-ethylpiperidine-1,3-dicarboxylate (2.06 g, 8.0 mmol) and N,O-dimethylhydroxylamine hydrochloride (273 mg, 8.95 mmol) in dry THF (21 mL) was added dropwise under argon at 0 °C. The reaction mixture was allowed to warm to rt for 3 h. The solution was then quenched with aq. saturated NH ₄ Cl at 0 °C. The aq. layer was extracted with EtOAc and the combined organic extracts were washed with brine, dried over anhyd. _Na2SO4 , filtered and concentrated to give the title compound (1.90 g, yield: 98%) as _a light brown oil.

HPLC-MS (Method E): Rt.: 3.17 min; ESI+ MS: m/z 242.0 [M+H] ⁺ .

Stage b. tert-Butyl-(Z)-3-(3-(dimethylamino)-2-methylacryloyl)piperidine-1-carboxylate

Starting from the compound obtained in step a (600 mg, 2.48 mmol) and following the procedure described in step b of Example 110, the title compound (735 mg) was obtained.

HPLC-MS (Method E): Rt.: 2.87 min; ESI+ MS: m/z 297.1 [M+H] ⁺ .

Stage c. The compound indicated in the title

Starting from the compound obtained in step b (735 mg, 2.48 mmol) and following the procedure described in Example 144, the title compound was obtained (29 mg, yield: 29% over 5 steps).

HPLC-MS (Method I): Rt.: 2.50 min; ESI+ MS: m/z 482.2 [M+H] ⁺ .

Example 238. 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2,5-dimethylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine

Step a. tert-Butyl (E)-3-(3-(dimethylamino)but-2-enoyl)piperidine-1-carboxylate

Starting from the compound obtained in step a of Example 110 (250 mg, 1.10 mmol) and 1,1-dimethoxy-N,N-dimethylethan-1-amine (176 mg, 1.32 mmol) and following the procedure described in step b of Example 110, the title compound (308 mg) was obtained.

HPLC-MS (Method E): Rt.: 2.87 min; ESI+ MS: m/z 297.1 [M+H] ⁺ .

Step b. The title compound

Starting from the compound obtained in step a (308 mg, 1.03 mmol) and following the procedure described in Example 144, the title compound was obtained (80 mg, yield: 14% over 6 steps).

HPLC-MS (Method I): Rt.: 2.97 min; ESI+ MS: m/z 482.2 [M+H] ⁺ .

Example 239. (S)-1-(7-(1-(2-Fluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N-((tetrahydro-2H-pyran-4-yl)methyl)methanamine

Step a. tert-Butyl (S)-3-acetylpiperidine-1-carboxylate

Methylmagnesium chloride (3 M in THF, 35.6 mL, 107 mmol) was added dropwise under argon to a stirred solution of 1-(tert-butyl)-3-ethyl-(S)-piperidine-1,3-dicarboxylate (5 g, 19.43 mmol) and N,O-dimethylhydroxylamine hydrochloride (2.27 g, 23.32 mmol) in dry THF (40 mL) at 0 °C. The reaction mixture was allowed to stir at 0 °C for 1 h. The solution was then quenched with aq. saturated NH ₄ Cl at 0 °C. The aq. layer was extracted with EtOAc and the combined organic extracts were washed with brine, dried over anhyd. _MgSO4 , filtered and concentrated to give the title compound (4.18 g, yield: 95%) as a light yellow oil.

HPLC-MS (Method K(f)): Rt.: 3.83 min; ESI+ MS: m/z 228.0 [M+H] ⁺ .

Step b. tert-Butyl (S,E)-3-(3-(dimethylamino)acryloyl)piperidine-1-carboxylate The compound obtained in step a (2.01 g, 8.84 mmol) and 1-tert-butoxy-N,N,N',N'-tetramethylmethanediamine (1.83 ml, 8.84 mmol) were mixed in a sealed reactor under argon atmosphere, and the mixture was stirred at 100 °C for 30 min. Thereafter, the reaction mixture was directly cooled to 0 °C over 15 min and then concentrated to dryness under reduced pressure to give the title compound as a yellow oil (2.49 g).

HPLC-MS (Method K(f)): Rt.: 4.98 min; ESI+ MS: m/z 283.3 [M+H] ⁺ .

Step c. tert-Butyl (S)-3-(2-bromopyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

A solution of the compound obtained in step b (2.50 g, 8.84 mmol) was dissolved in glacial AcOH (15 mL) and 5-bromo-1H-pyrazol-3-amine (1.56 g, 8.84 mmol) was added. The reaction mixture was stirred at 50 °C for 7 h. The solvent was evaporated and the residue was purified by flash chromatography on silica gel, hexane/EtOAc as eluents, to afford the title compound as a yellow sticky solid (2.45 g, yield: 70%).

HPLC-MS (Method L): Rt.: 7.68 min; ESI+ MS: m/z 396.1 [M+H] ⁺ .

Step d. tert-Butyl (S,E)-3-(2-methyl-3-styrylpyrazolo[1,5-a]pyrimidin-7-yl)piperidine-1-carboxylate

A solution of the compound obtained in step c (2.49 g, 6.30 mmol), (E)-4,4,5,5-tetramethyl-2-styryl-1,3,2-dioxaborolane (2.90 g, 12.60 mmol), Pd(dppf)Cl ₂ (140 mg, 0.17 mmol) and aqueous sodium carbonate solution (2 M, 10.7 mL, 21.42 mmol) in toluene/EtOAc (2:1, 21 mL) was degassed by bubbling with argon and stirred at 90 °C for 16 h. The reaction mixture was diluted with EtOAc, the organic layer was washed with aq. saturated Na ₂ CO ₃ solution, brine, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated. The residue was purified by flash chromatography on silica gel, DCM as eluent, to give the title compound as a yellow oil (647 mg, yield: 24%).

HPLC-MS (Method K(b)): Rt.: 7.07 min; ESI+ MS: m/z 419.1 [M+H] ⁺ .

Step e. (S,E)-2-Methyl-7-(piperidin-3-yl)-3-styrylpyrazolo[1,5-a]pyrimidine hydrochloride

Starting from the compound obtained in step d (647 mg, 1.54 mmol) and following the procedure described in step d of Example 110, the title compound was obtained (549 mg). This compound was used in the next step without further purification.

Step f. (S,E)-7-(1-(2-Fluorobenzyl)piperidin-3-yl)-2-methyl-3-styrylpyrazolo[1,5-a]pyrimidine

The compound obtained in step e (175 mg, 0.49 mmol) was dissolved in dry DCM (8 mL) and TEA (0.2 mL, 1.48 mmol) was added at rt. To this solution were added 2-fluorobenzaldehyde (0.1 mL, 0.99 mmol) and AcOH (0.003 mL, 0.49 mmol), after shaking for 5 min, sodium triacetoxyhydroborate (218 mg, 1 mmol) was added to the solution and the reaction mixture was kept at rt for 16 h. Then the reaction mixture was diluted with DCM, the organic layer was washed with aq. _{saturated Na2CO3} solution, then dried over _{anhydrous Na2SO4} and filtered. The solvent was evaporated and the residue was purified by flash chromatography on silica gel, DCM:MeOH as eluents, to give the title compound as a yellow oil (150 mg, yield: 67% over 2 steps).

HPLC-MS (Method K(a)): Rt.: 7.78 min; ESI+ MS: m/z 427.1 [M+H] ⁺ .

Stage g. (S)-7-(1-(2-Fluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde

To a solution of the compound obtained in step f (145 mg, 0.4 mmol) in acetone/water (6:1, 7 mL) were added _NaIO4 (218 mg, 1.02 mmol) and _OsO4 (10 mg, 0.04 mmol) successively at rt. After addition of _OsO4, the yellow solution turned black and a light brown solid precipitated. The resulting mixture was stirred at rt for 2 h, then it was filtered through a fritted glass funnel, the gray solid was washed with EtOAc. Then the organic phase was washed with aq. _{saturated Na2CO3} solution, brine and dried over anhyd. _Na2SO4 , _filtered and concentrated. The residue was purified by flash chromatography on silica gel, DCM:MeOH as eluents, to afford the title compound as a yellow solid (55 mg, yield: 45%). This yellow solid was precipitated in a minimum amount of MeOH, then filtered, the solid was washed with a minimum amount of MeOH, then hexane and dried in vacuo to afford the title compound with an enantiomeric excess of >90%.

HPLC-MS (Method K(d)): Rt.: 5.53 min; ESI+ MS: m/z 353.1 [M+H] ⁺ .

Stage h. Title compound

To a solution of the compound obtained in step g (50 mg, 0.14 mmol) in dry MeOH (2 mL) were added tetrahydro-2H-pyran-4-ylmethanamine (24.0 mg, 0.21 mmol) and drops of AcOH. The reaction mixture was shaken at rt for 15 min, sodium cyanotrihydroborate (9.0 mg, 0.14 mmol) was added and the reaction mixture was stirred at rt for 3 h. Then the solvent was evaporated and the reaction mixture was dissolved with DCM and poured into aqueous saturated NaHCO ₃ solution, the organic layer was separated and the aq. layer was extracted with DCM. The combined organic extracts were washed with brine, dried over anhydrous Na ₂ SO ₄ and filtered. The solvent was evaporated and the residue was purified by flash chromatography on silica gel, DCM:MeOH as eluents, to give the title compound (53 mg, yield: 79%).

HPLC-MS (Method M): Rt.: 12.77 min; ESI+ MS: m/z 452.2 [M+H] ⁺ .

This method was used to prepare Examples 240-242 using suitable starting materials.

Examples 243 and 244. (R)-4-((((7-((S)-1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)-1-methylpiperidin-2-one, (S)-4-((((7-((S)-1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)-1-methylpiperidin-2-one

Starting from 4-((((7-((S)-1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)-1-methylpiperidin-2-one, obtained according to a procedure similar to that described in Example 239, chiral preparative HPLC was performed [column Chiralpak AD-H, 20 x 250 mm; 5 μm; temperature: rt; eluent H-heptane/EtOH/Et ₂ NH 70/30/0.1 v/v/v; flow rate: 12 ml/min; Rt1: 13.7 min; Rt2: 17.2 min] to afford the title compounds.

Examples 245 and 246. (R)-5-((((7-((S)-1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidin-2-one and (S)-5-((((7-((S)-1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidin-2-one

Starting from 5-((((7-(1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidin-2-one, obtained according to a procedure similar to that described in Example 239, chiral preparative HPLC was performed [column Chiralpak IB, 20 x 250 mm; 5 μm; temperature: rt; eluent n-heptane/EtOH/Et ₂ NH 80/20/0.1 v/v/v; flow rate: 12 ml/min; Rt1: 19.8 min; Rt2: 27.3 min] to afford the title compounds.

Example 247. (S)-1-(4-((((7-(1-(3,4-Difluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one

Method 1:

Stage a. Ethyl (S)-1-(3,4-difluorobenzyl)piperidine-3-carboxylate

To a solution of ethyl (S)-piperidine-3-carboxylate (6.10 g, 38.80 mmol) in dry DCM (130 mL) cooled at 0 °C was added dropwise DIPEA (10.13 mL, 58.2 mmol) under argon atmosphere followed by the addition of 4-(bromomethyl)-1,2-difluorobenzene (4.96 mL, 38.80 mmol). The reaction mixture was allowed to warm to rt and stirred for 16 h. The organic layer was washed with aq. _{saturated Na2CO3} solution and brine. Then it was dried over anh. _Na2SO4 and _concentrated . The residue was purified by flash chromatography on silica gel, hexane:EtOAc as eluents, to give the title compound as a yellow oil (9.65 g, yield: 83%).

HPLC-MS (Method K(b)): Rt.: 4.58 min; ESI+ MS: m/z 284.0 [M+H] ⁺ .

Stage b. (S)-1-(1-(3,4-Difluorobenzyl)piperidin-3-yl)ethan-1-one

Starting with the compound obtained in step a (5.20 g, 18.35 mmol) and following the procedure described in step a of Example 239, the title compound was obtained as a light brown oil (4.61 g). This compound was used in the next step without further purification.

HPLC-MS (Method K(g)): Rt.: 13.03 min; ESI+ MS: m/z 254.0 [M+H] ⁺ .

Step c. (S,E)-1-(1-(3,4-Difluorobenzyl)piperidin-3-yl)-3-(dimethylamino)prop-2-en-1-one

Starting with the compound obtained in step b (3.39 g, 13.38 mmol) and following the procedure described in step b of Example 239, the title compound was obtained as a brown oil (4.10 g). This compound was used in the next step without further purification.

HPLC-MS (Method K(e)): Rt.: 5.28 min; ESI+ MS: m/z 309.0 [M+H] ⁺ .

Step d. (S)-3-Bromo-7-(1-(3,4-difluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidine

Starting from the compound obtained in step c (4.10 g, 13.30 mmol) and following the procedure described in step c of Example 239, the title compound was obtained as a thick brown oil (3.20 g, yield: 55% over 3 steps).

HPLC-MS (Method K(c)): Rt.: 5.57 min; ESI+ MS: m/z 421.0 [M+H] ⁺ .

Step f. (S,E)-7-(1-(3,4-Difluorobenzyl)piperidin-3-yl)-2-methyl-3-styrylpyrazolo[1,5-a]pyrimidine

Starting from the compound obtained in step d (2.16 g, 5.13 mmol) and following the procedure described in step d of Example 239, the title compound was obtained as a yellow sticky solid (1.94 g, yield: 80%).

HPLC-MS (Method K(a)): Rt.: 7.02 min; ESI+ MS: m/z 445.1 [M+H] ⁺ .

Step f. (S)-7-(1-(3,4-Difluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde

Starting from the compound obtained in step e (1.94 g, 4.36 mmol) and following the procedure described in step g of Example 239, the title compound was obtained as a white solid (500 mg, yield: 31%).

HPLC-MS (Method K(d)): Rt.: 5.60 min; ESI+ MS: m/z 3715.1 [M+H] ⁺ .

Step g. Title compound

Starting with the compound obtained in step f (500 mg, 1.35 mmol) and 1-(4-aminomethyl)piperidin-1-yl)ethan-1-one and following the procedure described in step h of Example 239, the title compound was obtained as a sticky brown solid (434 mg, yield: 62%).

HPLC-MS (Method E): Rt.: 3.10 min; ESI+ MS: m/z 511.2 [M+H] ⁺ .

Method 2:

Step a. Piperidin-4-ylmethanol hydrochloride

Starting with tert-butyl 4-(hydroxymethyl)piperidine-1-carboxylate (1.0 g, 4.64 mmol) and following the procedure from step d of Example 110, the title compound (704 mg) was obtained. This compound was used in the next step without further purification.

Stage b. 1-(4-(Hydroxymethyl)piperidin-1-yl)ethan-1-one

_To a solution of the compound obtained in step a (704 mg, 4.64 mmol) in acetone (16 mL) was added _K2CO3 (1.6 g, 11.6 mmol) followed by dropwise addition of acetic anhydride (0.52 mL, 5.57 mmol). The reaction mixture was stirred at rt for 3 h. It was then filtered through a pad of celite and the resulting white solid was washed with acetone several times. The combined filtrates were then concentrated under reduced pressure. The residue was purified by flash chromatography on silica gel, DCM:MeOH as eluents, to afford the title compound as a yellow oil (600 mg, yield: 82%).

HPLC-MS (Method E): Rt.: 1.00 min; ESI+ MS: m/z 158.0 [M+H] ⁺ .

Stage c. 1-Acetylpiperidine-4-carbaldehyde

To a cooled to 0°C solution of the compound obtained in step b (600 mg, 3.82 mmol) in chloroform (13 mL) was added Dess-Martin periodinane (1.78 g, 4.20 mmol) under argon atmosphere and the reaction mixture was allowed to warm to rt and stirred for 2 h. The resulting suspension was then filtered through a pad of celite and the resulting white solid was washed with chloroform several times. The combined filtrates were then concentrated under reduced pressure. The residue was dissolved in DCM and MP-carbonate resin (3.5 mmol/g loading, 3.2 g, 11.46 mmol) was added to the solution and the reaction mixture was stirred for 3 h. Then it was filtered through a fritted glass funnel and the resulting filtrate was concentrated under vacuum to give the desired title compound as a colorless oil (238 mg, yield: 40%). This compound should be stored in a freezer under argon for a short time because it is an unstable compound.

HPLC-MS (Method E): Rt.: 0.87 min; ESI+ MS: m/z 156.0 [M+H] ⁺ .

Step d. tert-Butyl (S)-((7-(1-(3,4-difluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)carbamate

To a solution of the compound obtained in step d (method 1) from Example 247 (839 mg, 1.99 mmol) in a dioxane/water mixture (5:1.5, 12 mL) were added potassium (((tert-butoxycarbonyl)amino)methyl)trifluoroborate (944 mg, 3.98 mmol), dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (327 mg, 0.8 mmol), K ₃ PO ₄ (3.38 g, 15.93 mmol) and allylpalladium(II) chloride dimer (61 mg, 0.17 mmol), the resulting mixture was degassed with argon for 5 min and heated at 100 °C for 16 h. It was then cooled to rt. and filtered through double filter paper, the resulting solid was washed with EtOAc several times and the combined filtrates were concentrated to dryness under vacuum. The residue was purified by flash chromatography on silica gel, DCM:MeOH as eluents, to give the title compound as an orange solid (556 mg, yield: 59%).

HPLC-MS (Method E): Rt.: 3.92 min; ESI+ MS: m/z 472.1 [M+H] ⁺ .

Step e. (S)-(7-(1-(3,4-Difluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methanamine dihydrochloride

Starting with the compound obtained in step d (455 mg, 0.96 mmol) and following the procedure described in step d of Example 110, the title compound was obtained (358 mg). This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 4.40 min; ESI+ MS: m/z 372.0 [M+H] ⁺ .

Step f. Title compound

To a solution of the compound obtained in step e (398 mg, 1.07 mmol) in dry MeOH (14 mL) was added TEA (0.37 mL, 2.68 mmol), followed by dropwise addition of the aldehyde obtained in step c (145 mg, 0.91 mmol) in dry MeOH (1 mL) and a few drops of AcOH. After vigorous stirring for 10 min, sodium cyanotrihydroborate (67.30 mg, 1.07 mmol) was added under argon atmosphere and the reaction mixture was stirred at rt for 3 h. The solvent was then evaporated under reduced pressure and the resulting residue was partitioned between DCM (30 mL) and aq. sat. NaHCO ₃ . The organic layer was separated, washed with aq. sat. _NaHCO3 solution, dried over _MgSO4 , filtered and concentrated in vacuo. The residue was purified by preparative HPLC (XBridge C ₁₈ column and 10 mM _NH4HCO3 / ₂₅ % w/w _NH4OH (99.8:0.12):ACN as eluents) to afford the title compound as a colourless oil (180 mg, yield: 32%).

HPLC-MS (Method E): Rt.: 3.10 min; ESI+ MS: m/z 511.2 [M+H] ⁺ .

This method (2) was used to obtain Example 248 using suitable starting materials:

Example 249. 7-((1-(4-Chlorobenzyl)piperidin-3-yl)methyl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine

Step a. tert-Butyl 3-(2-(methoxy(methyl)amino)-2-oxoethyl)piperidine-1-carboxylate

To a solution of 2-(1-(tert-butoxycarbonyl)piperidin-3-yl)acetic acid (2 g, 8.22 mmol) in DCM (60 mL) cooled at 0 °C were added sequentially N,O-dimethylhydroxylamine (653 mg, 10.69 mmol), EDC.HCl (2.36 g, 12.33 mmol), HOBt (1.89 g, 12.33 mmol) and TEA (4.6 mL, 32.9 mmol) and the reaction mixture was allowed to warm to rt and stirred for 16 h. Then it was partitioned between DCM and 2 N HCl. The organic layer was separated, washed with 2 N HCl, 1 N NaOH, brine, dried over anhydrous. _Na2SO4 , _filtered and concentrated in vacuo to give the title compound as a colourless viscous oil (1.70 g, yield: 72%). This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 2.83 min; ESI+ MS: m/z 287.1 [M+H] ⁺ .

Step b. tert-Butyl 3-(2-oxopropyl)piperidine-1-carboxylate

To a stirred solution of the compound obtained in step a (1.7 g, 5.94 mmol) in anhydrous THF (15 mL) was added dropwise methylmagnesium chloride (3 M in THF, 3.0 mL, 9 mmol) under argon atmosphere at 0 °C. The reaction mixture was allowed to warm to rt and stirred for 2 h. The reaction mixture was then partitioned between Et ₂ O and 2 N HCl. The organic layer was separated, washed with brine, dried over anhydrous Na ₂ SO ₄ , filtered and concentrated in vacuo to give the title compound as a colorless oil (1.32 g, yield: 92%). This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 3.00 min; ESI+ MS: m/z 242.1 [M+H] ⁺ .

Step c. tert-Butyl (E)-3-(4-(dimethylamino)-2-oxobut-3-en-1-yl) piperidine-1-carboxylate

Starting from the compound obtained in step b (1.32 g, 5.47 mmol) and following the procedure described in step b of Example 110, the title compound (1.62 g) was obtained. This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 2.67 min; ESI+ MS: m/z 297.0 [M+H] ⁺ .

Step d. tert-Butyl 3-((3-bromo-2-methylpyrazolo[1,5-a]pyrimidin-7-yl)methyl)piperidine-1-carboxylate

Starting from the compound obtained in step c (800 mg, 2.7 mmol) and following the procedure described in step a of Example 121, the title compound was obtained (640 mg, yield: 57%).

HPLC-MS (Method E): Rt.: 3.73 min; ESI+ MS: m/z 409.1 [M+H] ⁺ .

Step E. tert-Butyl-3-((2-methyl-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidin-7-yl)methyl)piperidin-1-carboxylate

Starting from the compound obtained in step d (220 mg, 0.53 mmol) and following the procedure described in step a of Example 114, the title compound was obtained (123 mg, yield: 55%).

HPLC-MS (Method E): Rt.: 3.42 min; ESI+ MS: m/z 408.1 [M+H] ⁺ .

Step f. 2-Methyl-7-(piperidin-3-ylmethyl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine dihydrochloride

Starting from the compound obtained in step e (123 mg, 0.30 mmol) and following the procedure described in step d of Example 110, the title compound was obtained (104 mg). This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 2.47 min; ESI+ MS: m/z 308.0 [M+H] ⁺ .

Step g. Title compound

Starting from the compound obtained in step f (120 mg, 0.35 mmol) and according to the procedure described in step e of Example 110, the title compound was obtained (90 mg, yield: 59%).

HPLC-MS (Method E): Rt.: 3.98 min; ESI+ MS: m/z 432.1 [M+H] ⁺ .

This method was used to prepare Example 250 using the appropriate starting materials:

Example 251. 1-(7-((1-(4-Chlorobenzyl)piperidin-3-yl)methyl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-dimethylmethanamine

Stage a. tert-Butyl-3-((2-methylpyrazolo[1,5-a]pyrimidin-7-yl)methyl)piperidine-1-carboxylate

Starting from the compound obtained in step c of Example 249 (2.15 g, 7.25 mmol) and following the procedure described in step a of Example 144, the title compound was obtained (1.5 g, yield: 60%).

HPLC-MS (Method E): Rt.: 3.20 min; ESI+ MS: m/z 331.0 [M+H] ⁺ .

Step b. 2-Methyl-7-(piperidin-3-ylmethyl)pyrazolo[1,5-a]pyrimidine hydrochloride

Starting from the compound obtained in step a (1.0 g, 3.03 mmol) and following the procedure described in step d of Example 110, the title compound was obtained (807 mg). This compound was used in the next step without further purification.

HPLC-MS (Method E): Rt.: 2.12 min; ESI+ MS: m/z 231.0 [M+H] ⁺ .

Stage c. 7-((1-(4-Chlorobenzyl)piperidin-3-yl)methyl)-2-methylpyrazolo[1,5-a]pyrimidine

Starting from the compound obtained in step b (420 mg, 1.57 mmol) and according to the procedure described in step e of Example 110, the title compound was obtained (245 mg, yield: 59%).

HPLC-MS (Method E): Rt.: 3.77 min; ESI+ MS: m/z 355.1 [M+H] ⁺ .

Step d. 7-((1-(4-Chlorobenzyl)piperidin-3-yl)methyl)-2-methylpyrazolo[1,5-a]pyrimidine-3-carbaldehyde

Starting from the compound obtained in step c (345 mg, 0.97 mmol) and following the procedure described in step a of Example 120, the title compound was obtained (290 mg, yield: 54%).

HPLC-MS (Method E): Rt.: 3.70 min; ESI+ MS: m/z 383.1 [M+H] ⁺ .

Stage e. The title compound

Starting from the compound obtained in step d (290 mg, 0.75 mmol) and dimethylamine (0.94 ml, 1.89 mmol) and following the procedure described in step e of Example 110, the title compound was obtained (31 mg, yield: 8%).

HPLC-MS (Method I): Rt.: 2.95 min; ESI+ MS: m/z 412.2 [M+H] ⁺ .a

This method was used to prepare Examples 252 and 253 using suitable starting materials.

BIOLOGICAL ACTIVITY

Pharmacological research

Analysis of the α ₂ δ-1 subunit of human calcium channels Ca _v 2.2

Membranes enriched with human α ₂ δ-1 (2.5 μg) were incubated with 15 nM radiolabeled [ ³ H]-gabapentin in assay buffer containing 10 mM Hepes-KOH, pH 7.4. NSB (non-specific binding) was measured by adding 10 μM pregabalin. Binding of test compound was measured either at a single concentration (% inhibition at 1 or 10 μM) or at five different concentrations to determine affinity (Ki) values. After incubation for 60 min at 27°C, the binding reaction was terminated by filtration through Multiscreen GF/C (Millipore) presoaked with 0.5% polyethyleneimine on a Vacuum Manifold Station, followed by 3 washes with ice-cold filtration buffer containing 50 mM Tris-HCl, pH 7.4. The filter plates were dried at 60°C for 1 h and 30 μl of scintillation fluid were added to each well before radioactivity was counted. Readings were performed on a Trilux 1450 Microbeta radioactivity counter (Perkin Elmer).

Human oi receptor radioligand assay

Transfected HEK-293 membranes (7 μg) were incubated with 5 nM [ ³ H](+)-pentazocine in assay buffer containing 50 mM Tris-HCl at pH 8. NBS (non-specific binding) was measured by adding 10 μM haloperidol. Binding of test compound was measured either at a single concentration (% inhibition at 1 or 10 μM) or at five different concentrations to determine affinity (Ki) values. Plates were incubated at 37°C for 120 min. After the incubation period, the reaction mixture was then loaded onto Multiscreen HTS, FC plates (Millipore), filtered, and the plates were washed three times with ice-cold 10 mM Tris-HCL (pH 7.4). The filters were dried and counted at approximately 40% efficiency in a MicroBeta scintillation counter (Perkm-Elmer) using EcoScint liquid scintillation cocktail.

Results

Since the present invention is directed to providing compounds or chemically related species of compounds which act as dual acting ligands for the _α2δ subunit of voltage-dependent calcium channels and the _σ1 receptor, a highly preferred embodiment is one in which the compounds are selected from compounds which act as dual acting ligands for the _α2δ subunit of voltage-dependent calcium channels and the _σ1 receptor, and especially compounds which are characterized by binding expressed as K _i according to the following scales.

Κ _i (σ ₁ ) is preferably <1000 nM, more preferably <500 nM, even more preferably <100 nM.

Κ _i ((α ₂ δ-1) is preferably <10000 nM, more preferably <5000 nM, or even more preferably <500 nM.

The following scale was chosen to represent σ ₁ -receptor binding, expressed as K _i :

Preferably, if K _i (σ ₁ ) >1000 nM, the following scale was chosen to represent binding to the σ1 receptor:

or inhibition ranges from 1% to 50%.

The following scale was chosen to represent binding to the _α2δ -1 subunit of voltage-gated calcium channels, expressed as K _i :

Preferably, if Κ _i (α ₂ δ-1)>5000 nM, the following scale was chosen to represent the binding of the α ₂ δ-1 subunit of voltage-gated calcium channels:

or inhibition ranges from 1% to 50%.

Table with examples of binding to the σ ₁ receptor and the α ₂ δ-1 subunit of the voltage-gated calcium channel

All compounds obtained in the present application demonstrate binding to the α ₂ δ-1 subunit of voltage-dependent calcium channels and to the σ ₁ receptor, in particular, showed the following binding results.

Claims (95)

1. A compound of general formula (I), Where m is equal to 1, 2, 3, or 4; n is equal to 1 or 2; t is equal to 0 or 1; X is selected from the group consisting of the bond, –[CH ₂ ] _p -, -[CH ₂ ] _p NR _x [CH ₂ ] _q -, -[CH ₂ ] _p O[CH ₂ ] _q -, -[CH ₂ ] _p NR _x C(O)[CH ₂ ] _q - and –[CH ₂ ] _p NR _x CH(CH ₃ )-; Where p is 0, 1, 2, 3, or 4; q is equal to 0, 1, 2, 3, or 4; R _x is selected from the group consisting of hydrogen, unsubstituted C _1-6 alkyl, and C _1-6 alkyl substituted with one or more halogen atoms; R ₁ is selected from the group consisting of hydrogen, unsubstituted C _1-6 alkyl, halogen, haloC _1-6 alkyl, -OR ₆ , -NR ₆ R ₆ ', -CN, C _3-7 cycloalkyl, phenyl and 5-6-membered heterocyclyl containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur; R ₆ is selected from the group consisting of hydrogen, unsubstituted C _1-6 alkyl, unsubstituted phenyl, unsubstituted C _1-6 alkylC _3-7 cycloalkyl, substituted or unsubstituted C _1-6 alkylphenyl and substituted or unsubstituted C _1-6 alkylheterocyclyl, where heterocyclyl is a 5-6-membered heterocyclyl containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur; wherein said C _1-6 alkylphenyl, when substituted, is substituted by one or more substituents selected from halogen and -[CH ₂ ] _r OR ₁₄ ; wherein said C _1-6 alkylheterocyclyl, when substituted, is substituted with one or more substituents selected from halogen, -R ₁₄ , =O, -S(O) ₂ R ₁₄ , -C(O)R ₁₄ and -C(O)NR ₁₄ R _14' ; R ₆ ' is selected from the group consisting of hydrogen and unsubstituted C _1-6 alkyl; alternatively R ₆ and R ₆ ' taken together with the nitrogen atom to which they are attached form a substituted or unsubstituted 5- to 6-membered heterocyclyl containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur, wherein said heterocyclyl, when substituted, is substituted with one or more substituents selected from -R ₁₄ , -[CH ₂ ] _r OR ₁₄ , =O, -[CH ₂ ] _r NR ₁₄ R _14' , S(O) ₂ R ₁₄ , –CN, -C(O)R ₁₄ and -C(O)NR ₁₄ R _14' ; where R ₁₄ and R _14' are independently selected from hydrogen and unsubstituted C _1-6 alkyl; R ₂ is selected from the group consisting of hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _3-7 cycloalkyl, unsubstituted C _1-6 alkylC _3-7 cycloalkyl, halogen and -OR ₇ ; R ₇ is selected from the group consisting of hydrogen and unsubstituted C _1-6 alkyl; R ₃ is selected from the group consisting of hydrogen and unsubstituted C _1-6 alkyl; R ₄ is selected from the group consisting of unsubstituted C _1-6 alkyl, unsubstituted C _3-7 cycloalkyl, substituted or unsubstituted phenyl, and substituted or unsubstituted 5-6-membered heterocyclyl containing one nitrogen heteroatom or one oxygen heteroatom; wherein phenyl in R ₄ , when substituted, is substituted by one or more substituents selected from halogen, -R ₄₁ , -[CH ₂ ] _r OR ₄₁ , –CN and haloC _1-6 alkyl; where R ₄₁ is selected from hydrogen and unsubstituted C _1-6 alkyl; where heterocyclyl in R ₄ , in the case of substitution, is substituted by one halogenC _1-6 alkyl; R ₅ and R ₅ ' are independently selected from the group consisting of hydrogen, unsubstituted C _1-6 alkyl, and C _1-6 alkyl substituted with one -OH substituent; where r is 0, 1, 2, or 3; or a stereoisomer or its corresponding salt; where the following connection is excluded: 2. The compound of claim 1, wherein the compound of formula (I) is a compound of formula (I'), 3. The compound of claim 1, wherein the compound of formula (I) is a compound of formula (I ² '), 4. The compound of claim 1, wherein the compound of formula (I) is a compound of formula (I ³ '), 5. A compound according to any one of claims 1, 3 and 4, where t equals 0 and n equals 1. 6. A compound according to any one of claims 1 to 5, wherein R ₄ is substituted or unsubstituted phenyl. 7. A compound of formula (I) as defined in claim 1, wherein R ₁ is hydrogen, bromine, chlorine, -CN, methyl, ethyl, isopropyl, -CF ₃ , -OH, methoxy, -O-isopropyl, -NH ₂ , -NHCH ₃ , -N(CH ₃ ) ₂ , -N(CH ₃ )(CH ₂ -cyclopropyl), -N(CH ₃ )(benzyl), -N(CH ₃ )(piperidine), -N(CH ₂ CF ₃ )(CH ₂ -tetrahydropyran), cyclopropyl, or a substituted or unsubstituted group selected from phenyl, pyridine, piperidine, pyrrolidine, piperazine, pyrimidine, pyrazole, isoxazole, isothiazole, imidazole, morpholine, thiomorpholine, tetrahydropyran, tetrahydrofuran and thiophene; wherein the said group, in the case of substitution, is substituted by one or more substituents selected from halogen, R ₁₁ , -[CH ₂ ] _r OR ₁₁ , =O, -[CH ₂ ] _r NR ₁₁ R _11' , -S(O) ₂ R ₁₁ , –CN, halogenC _1-6 alkyl, -C(O)R ₁₁ , -C(O)NR ₁₁ R _11' ; where R ₁₁ and R _11' are independently selected from hydrogen, unsubstituted C _1-6 alkyl, unsubstituted C _1-6 alkylC _3-7 cycloalkyl, unsubstituted C _3-7 cycloalkyl and 5-6-membered heterocyclyl containing one or more heteroatoms selected from the group consisting of nitrogen, oxygen and/or sulfur, wherein said heterocyclyl is unsubstituted or substituted with one R ₂₁ or -[CH ₂ ] _r NR ₂₁ R _21' , wherein R ₂₁ and R _21' are independently selected from hydrogen and unsubstituted C _1-6 alkyl; where r is 0, 1, 2, or 3; and X, R ₂ , R ₃ , R ₄ , R ₅ , R _5' , m, n and t are as defined in paragraph 1, where the following connections are excluded: And . 8. A connection according to any one of paragraphs 1-7, selected from the following: 1 7-(1-Benzylpiperidin-3-yl)-2-bromopyrazolo[1,5- a ]pyrimidine 2 7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidine 3 7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 4 7-(1-Benzylpiperidin-3-yl)-2-ethylpyrazolo[1,5- a ]pyrimidine 5 7-(1-Benzylpiperidin-3-yl)-3-bromopyrazolo[1,5- a ]pyrimidine 6 7-(1-Benzylpiperidin-3-yl)-3-bromo-2,6-dimethylpyrazolo[1,5- a ]pyrimidine 7 7-(1-Benzylpiperidin-3-yl)-3-bromo-6-methylpyrazolo[1,5- a ]pyrimidine 8 N -(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)acetamide 9 N -(7-(1-Benzylpiperidin-3-yl)-3-methylpyrazolo[1,5- a ]pyrimidin-2-yl)acetamide 10 7-(1-Benzylpiperidin-3-yl)-3-bromo-2-methylpyrazolo[1,5- a ]pyrimidine 11 7-(1-Benzylpiperidin-3-yl)-3-bromo-2-ethylpyrazolo[1,5- a ]pyrimidine 12 7-(1-Benzylpiperidin-3-yl)-2-phenylpyrazolo[1,5- a ]pyrimidine 13 7-(1-Benzylpiperidin-3-yl)-2-(4-ethoxyphenyl)pyrazolo[1,5- a ]pyrimidine 14 7-(1-Benzylpiperidin-3-yl)-2-(2-fluorophenyl)pyrazolo[1,5- a ]pyrimidine 15 7-(1-Benzylpiperidin-3-yl)-2-(4-chlorophenyl)pyrazolo[1,5- a ]pyrimidine 16 7-(1-Benzylpiperidin-3-yl)-2-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 17 7-(1-Benzylpiperidin-3-yl)-2-(pyridin-3-yl)pyrazolo[1,5- a ]pyrimidine 18 7-(1-Benzylpiperidin-3-yl)-2-(3,5-dichloropyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 19 7-(1-Benzylpiperidin-3-yl)-2-(thiophen-2-yl)pyrazolo[1,5- a ]pyrimidine 20 4-(7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl)isothiazole 21 7-(1-Benzylpiperidin-3-yl)-2-(1-methyl- 1H- imidazol-5-yl)pyrazolo[1,5- a ]pyrimidine 22 4-(7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl) -N , N -dimethylaniline 23 7-(1-Benzylpiperidin-3-yl)-2-(pyrimidin-5-yl)pyrazolo[1,5- a ]pyrimidine 24 5-(7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl)pyridin-2-amine 25 7-(1-Benzylpiperidin-3-yl)-2-(1-methyl- 1H- pyrazol-4-yl)pyrazolo[1,5- a ]pyrimidine 26 7-(1-Benzylpiperidin-3-yl)-2-(pyridin-2-yl)pyrazolo[1,5- a ]pyrimidine 27 7-(1-Benzylpiperidin-3-yl)-2-(2-methoxypyridin-3-yl)pyrazolo[1,5- a ]pyrimidine 28 7-(1-Benzylpiperidin-3-yl)-2-(6-methoxypyridin-3-yl)pyrazolo[1,5- a ]pyrimidine 29 7-(1-Benzylpiperidin-3-yl)-2-(2-methoxyphenyl)pyrazolo[1,5- a ]pyrimidine 30 7-(1-Benzylpiperidin-3-yl)-2-(6-methoxypyridin-2-yl)pyrazolo[1,5- a ]pyrimidine 31 7-(1-Benzylpiperidin-3-yl)-2-(5-methoxypyridin-3-yl)pyrazolo[1,5- a ]pyrimidine 32 7-(1-Benzylpiperidin-3-yl)-2-(2-methoxypyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 33 7-(1-Benzylpiperidin-3-yl)-2-(3-methoxypyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 34 7-(1-Benzylpiperidin-3-yl)-2-(4-methoxypyridin-3-yl)pyrazolo[1,5- a ]pyrimidine 35 7-(1-Benzylpiperidin-3-yl)-3-phenylpyrazolo[1,5- a ]pyrimidine 36 7-(1-Benzylpiperidin-3-yl)-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 37 7-(1-Benzylpiperidin-3-yl)-3-(pyridin-3-yl)pyrazolo[1,5- a ]pyrimidine 38 7-(1-Benzylpiperidin-3-yl)-3-(2-methoxypyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 39 7-(1-Benzylpiperidin-3-yl)-3-(4-ethoxyphenyl)pyrazolo[1,5- a ]pyrimidine 40 7-(1-Benzylpiperidin-3-yl)-3-(2-methoxypyridin-3-yl)pyrazolo[1,5- a ]pyrimidine 41 7-(1-Benzylpiperidin-3-yl)-6-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 42 7-(1-Benzylpiperidin-3-yl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 43 7-(1-Benzylpiperidin-3-yl)-3-(2-methoxypyridin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 44 7-(1-Benzylpiperidin-3-yl)-2-methyl-3-phenylpyrazolo[1,5- a ]pyrimidine 45 7-(1-Benzylpiperidin-3-yl)-3-(4-ethoxyphenyl)-2-methylpyrazolo[1,5- a ]pyrimidine 46 7-(1-Benzylpiperidin-3-yl)-3-(2-methoxypyridin-4-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 47 4-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl) -N , N -dimethylaniline 48 7-(1-Benzylpiperidin-3-yl)-3-(2-fluorophenyl)-2-methylpyrazolo[1,5- a ]pyrimidine 49 7-(1-Benzylpiperidin-3-yl)-2-methyl-3-(3-methylpyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 50 7-(1-Benzylpiperidin-3-yl)-3-(2-fluoropyridin-4-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 51 7-(1-Benzylpiperidin-3-yl)-2-methyl-3-(2-methylpyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 52 7-(1-Benzylpiperidin-3-yl)-3-(3-fluoropyridin-4-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 53 7-(1-Benzylpiperidin-3-yl)-2-methyl-3-(2-(trifluoromethyl)pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 54 7-(1-Benzylpiperidin-3-yl)-3-(2-ethylpyridin-4-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 55 3-(3-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)phenyl)-5-methyl-1,2,4-oxadiazole 56 2-(3-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)phenyl)-5-methyl-1,3,4-oxadiazole 57 7-(1-Benzylpiperidin-3-yl)-3-(3-methoxypyridin-4-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 58 7-(1-Benzylpiperidin-3-yl)-2,6-dimethyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 59 7-(1-Benzylpiperidin-3-yl)-2,5-dimethyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 60 7-(1-Benzylpiperidin-3-yl)-2-ethyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 61 1-(1-(3-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5 -a ]pyrimidin-3-yl)phenyl) -1H- 1,2,3-triazol-4-yl) -N -methylmethanamine 62 1-(4-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)pyridin-2-yl)-N-methylmethanamine 63 7-(1-(2-Fluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 64 7-(1-Butylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 65 7-(1-(2,6-Difluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 66 2-Methyl-7-(1-(pyridin-2-ylmethyl)piperidin-3-yl)pyrazolo[1,5- a ]pyrimidine 67 2-Methyl-7-(1-phenethylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidine 68 3-((3-(2-Methylpyrazolo[1,5- a ]pyrimidin-7-yl)piperidin-1-yl)methyl)phenol 69 7-(1-Ethylpiperidin-3-yl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 70 2-Methyl-7-(1-propylpiperidin-3-yl)-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 71 7-(1-Isobutylpiperidin-3-yl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 72 2-Methyl-7-(1-(pyridin-2-ylmethyl)piperidin-3-yl)-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 73 6-Methyl-7-(1-phenethylpiperidin-3-yl)-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 74 6-Methyl-7-(1-(pyridin-2-ylmethyl)piperidin-3-yl)-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 75 2-Methyl-7-(1-(2-methylbenzyl)piperidin-3-yl)-3-(pyridin-4-yl)pyrazolo[1,5-a]pyrimidine 76 2-Methyl-7-(1-(4-methylbenzyl)piperidin-3-yl)-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 77 2-Methyl-7-(1-(3-methylbenzyl)piperidin-3-yl)-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 78 7-(1-Benzylpiperidin-3-yl)-2-(pyrrolidin-1-yl)pyrazolo[1,5- a ]pyrimidine 79 2-((7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl)(methyl)amino)ethanol 80 N ¹ -(7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl) -N ¹ -methylethane-1,2-diamine 81 N ¹ -(7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl)- N ¹ , N ² -dimethylethane-1,2-diamine 82 7-(1-Benzylpiperidin-3-yl) -N -methyl- N- (piperidin-4-yl)pyrazolo[1,5- a ]pyrimidin-2-amine 83 N ¹ -(7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl) -N ² -methylethane-1,2-diamine 84 ( R )-1-(7-(( R )-1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl) -N -methylpyrrolidin-3-amine 85 ( S )-1-(7-(( S )-1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl) -N -methylpyrrolidin-3-amine 86 ( S )-1-(7-(( R )-1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl) -N -methylpyrrolidin-3-amine 87 ( R )-1-(7-(( S )-1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl) -N- methylpyrrolidin-3-amine 88 7-(1-Benzylpiperidin-3-yl)-3-(pyrrolidin-1-yl)pyrazolo[1,5- a ]pyrimidine 89 7-(1-Benzylpiperidin-3-yl)-2-methyl-3-(pyrrolidin-1-yl)pyrazolo[1,5- a ]pyrimidine 90 7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-amine 91 7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-carbonitrile 92 1-(7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl) -N , N- dimethylmethanamine 93 1-(7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl) -N- methylmethanamine 94 N -Benzyl-1-(7-(1-benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-yl)methanamine 95 (7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methanol 96 1-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5 -a ]pyrimidin-3-yl) -N- methylmethanamine 97 N -((7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-2-phenylethanamine 98 N -Benzyl-1-(7-(1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methanamine 99 (7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methanamine 100 7-(1-Benzylpiperidin-3-yl)-2-methyl-3-(piperazin-1-ylmethyl)pyrazolo[1,5- a ]pyrimidine 101 3-((Benzyloxy)methyl)-7-(1-benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 102 7-(1-Benzylpiperidin-3-yl)-2-methyl-3-(phenoxymethyl)pyrazolo[1,5- a ]pyrimidine 103 3-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)propan-1-amine 104 7-(1-Benzylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-2-ol 105 7-(1-Benzylpiperidin-3-yl)-3-bromopyrazolo[1,5- a ]pyrimidin-2-ol 106 ( S )-2-(( R )-3-(2-Methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidin-7-yl)piperidin-1-yl)-2-phenylethanol 107 ( S )-2-(( S )-3-(2-Methyl-3-(pyridin-4-yl)pyrazolo[1,5 -a ]pyrimidin-7-yl)piperidin-1-yl)-2-phenylethanol 108 ( R )-2-(( S )-3-(2-Methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidin-7-yl)piperidin-1-yl)-2-phenylethanol 109 ( R )-2-(( R )-3-(2-Methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidin-7-yl)piperidin-1-yl)-2-phenylethanol 110 2-Bromo-7-(1-(4-chlorobenzyl)piperidin-3-yl)pyrazolo[1,5- a ]pyrimidine 111 2-Bromo-7-(1-(3-chlorobenzyl)piperidin-3-yl)pyrazolo[1,5- a ]pyrimidine 112 2-Bromo-7-(1-(3,4-dichlorobenzyl)piperidin-3-yl)pyrazolo[1,5- a ]pyrimidine 113 2-Bromo-7-(1-(3,4-difluorobenzyl)piperidin-3-yl)pyrazolo[1,5- a ]pyrimidine 114 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-(2-methoxypyridin-3-yl)pyrazolo[1,5-a]pyrimidine 115 3-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)pyrazolo[1,5-a]pyrimidin-2-yl)pyridin-2-ol 116 7-(1-(3-Chlorobenzyl)piperidin-3-yl)-2-(2-methoxypyridin-3-yl)pyrazolo[1,5- a ]pyrimidine 117 3-(7-(1-(3-Chlorobenzyl)piperidin-3-yl)pyrazolo[1,5 -a ]pyrimidin-2-yl)pyridin-2-ol 118 7-(1-(3,4-Dichlorobenzyl)piperidin-3-yl)-2-(2-methoxypyridin-3-yl)pyrazolo[1,5- a ]pyrimidine 119 7-(1-(3,4-Difluorobenzyl)piperidin-3-yl)-2-(2-methoxypyridin-3-yl)pyrazolo[1,5- a ]pyrimidine 120 1-(2-Bromo-7-(1-(4-chlorobenzyl)piperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 121 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 122 7-(1-(3-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 123 7-(1-(3,4-Dichlorobenzyl)piperidin-3-yl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 124 7-(1-(2,4-Dichlorobenzyl)piperidin-3-yl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 125 7-(1-(3,4-Difluorobenzyl)piperidin-3-yl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 126 2-Methyl-3-(pyridin-4-yl)-7-(1-(4-(trifluoromethyl)benzyl)piperidin-3-yl)pyrazolo[1,5- a ]pyrimidine 127 7-(1-Isopentylpiperidin-3-yl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 128 3-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N , N -dimethylbenzamide 129 4-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)benzamide 130 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-(pyrimidin-5-yl)pyrazolo[1,5- a ]pyrimidine 131 5-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)pyrimidin-2-amine 132 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-(1-methyl-1 H -pyrazol-4-yl)pyrazolo[1,5- a ]pyrimidine 133 4-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)-3,5-dimethylisoxazole 134 (4-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)pyridin-2-yl)methanol 135 (5-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)pyridin-2-yl)methanol 136 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-3-(2-ethoxypyridin-4-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 137 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-3-(2-(cyclopropylmethoxy)pyridin-4-yl)-2-methylpyrazolo[1,5- a ]pyrimidine 138 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-(1-methyl- 1H- imidazol-5-yl)pyrazolo[1,5- a ]pyrimidine 139 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-(pyrimidin-4-yl)pyrazolo[1,5- a ]pyrimidine 140 4-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)pyrimidin-2-amine 141 7-(1-(4-Chlorobenzyl)piperidin-3-yl) -N , N ,2-trimethylpyrazolo[1,5-a]pyrimidin-3-amine 142 7-(1-Benzylpiperidin-3-yl) -N , N ,2-trimethylpyrazolo[1,5 -a ]pyrimidin-3-amine 143 N -Benzyl-7-(1-benzylpiperidin-3-yl) -N ,2-dimethylpyrazolo[1,5- a ]pyrimidin-3-amine 144 N -Benzyl-1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methanamine 145 N -Benzyl-1-(7-(1-(4-chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -methylmethanamine 146 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -(4-fluorobenzyl)methanamine 147 (4-((((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)phenyl)methanol 148 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -(pyridin-4-ylmethyl)methanamine 149 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -(thiophen-2-ylmethyl)methanamine 150 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((5-methylthiophen-2-yl)methyl)methanamine 151 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((1-methyl-1 H -pyrazol-3-yl)methyl)methanamine 152 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((5-methyl-1,3,4-oxadiazol-2-yl)methyl)methanamine 153 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-2-phenylethan-1-amine 154 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-2-(4-methoxyphenyl)ethan-1-amine 155 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)ethanamine 156 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-2,2,2-trifluoroethane-1-amine 157 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5 -a ]pyrimidin-3-yl) -N- (cyclopropylmethyl)methanamine 158 2-(((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)ethan-1-ol 159 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)propan-2-amine 160 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-2-methylpropan-1-amine 161 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-3-methylbutan-1-amine 162 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-2-isopropoxyethane-1-amine 163 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-4-methoxybutan-1-amine 164 ( 2S , 6R )-4-((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-2,6-dimethylmorpholine 165 4-((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)morpholine 166 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-2-morpholinoethane-1-amine 167 4-((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)thiomorpholine 168 4-((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)thiomorpholine-1,1-dioxide 169 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-(piperidin-1-ylmethyl)pyrazolo[1,5- a ]pyrimidine 170 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-3-((4-(methoxymethyl)piperidin-1-yl)methyl)-2-methylpyrazolo[1,5- a ]pyrimidine 171 1-((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)piperidine-4-carboxamide 172 1-((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)piperidine-4-carbonitrile 173 4-((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)piperazin-2-one 174 1-(4-((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)piperazin-1-yl)ethan-1-one 175 7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methyl-3-((4-(methylsulfonyl)piperazin-1-yl)methyl)pyrazolo[1,5- a ]pyrimidine 176 1-(3-(((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)propyl)pyrrolidin-2-one 177 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((4-fluorotetrahydro-2 H -pyran-4-yl)methyl)methanamine 178 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-2-(tetrahydro-2 H -pyran-4-yl)ethan-1-amine 179 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((1-(methylsulfonyl)piperidin-4-yl)methyl)methanamine 180 1-(4-((((7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one 181 1-(7-(1-(3-Fluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 182 1-(7-(1-(3,4-Difluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 183 4-((3-(2-Methyl-3-((((tetrahydro-2 H -pyran-4-yl)methyl)amino)methyl)pyrazolo[1,5- a ]pyrimidin-7-yl)piperidin-1-yl)methyl)benzonitrile 184 1-(2-Methyl-7-(1-((6-(trifluoromethyl)pyridin-3-yl)methyl)piperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 185 1-(2-Methyl-7-(1-((tetrahydro-2 H -pyran-4-yl)methyl)piperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 186 1-(7-(1-(2,4-Dichlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N , N -dimethylmethanamine 187 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-ethylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 188 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-cyclopropylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 189 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methoxypyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 190 1-(2-Chloro-7-(1-(4-chlorobenzyl)piperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 191 1-(2-Chloro-7-(1-isopentylpiperidin-3-yl)pyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 192 1-(4-((((2-Chloro-7-(1-isopentylpiperidin-3-yl)pyrazolo[1,5-a]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one 193 ( S )-1-(4-((((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one 194 ( R )-1-(4-((((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one 195 ( R )- N -((7-(( R )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-1-phenylethan-1-amine 196 ( R )- N -((7-(( S )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)methyl)-1-phenylethan-1-amine 197 ( S )- N -((7-(( R )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-1-phenylethan-1-amine 198 ( S )- N -((7-(( S )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-1-phenylethan-1-amine 199 ( S )-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 200 ( R )-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 201 (+/-)-1-(7-(( R/S )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((( S/R )-tetrahydrofuran-3-yl)methyl)methanamine 202 1-(7-(( R )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((( R )-tetrahydrofuran-3-yl)methyl)methanamine 203 1-(7-(( S )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((( S )-tetrahydrofuran-3-yl)methyl)methanamine 204 ( S )-1-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl) -N -((tetrahydro- 2H -pyran-4-yl)methyl)methanamine 205 ( R )-1-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl) -N -((tetrahydro- 2H -pyran-4-yl)methyl)methanamine 206 ( S )-1-(7-(1-(4-Fluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 207 ( R )-1-(7-(1-(4-Fluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 208 ( S )-3-((3-(2-Methyl-3-((((tetrahydro-2 H -pyran-4-yl)methyl)amino)methyl)pyrazolo[1,5- a ]pyrimidin-7-yl)piperidin-1-yl)methyl)benzonitrile 209 ( R )-3-((3-(2-Methyl-3-((((tetrahydro-2 H -pyran-4-yl)methyl)amino)methyl)pyrazolo[1,5- a ]pyrimidin-7-yl)piperidin-1-yl)methyl)benzonitrile 210 ( S )-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N , N -dimethylmethanamine 211 ( R )-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N , N -dimethylmethanamine 212 ( R )-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -methylmethanamine 213 ( S )-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -methylmethanamine 214 (( S )-1-(7-(1-Benzylpiperidin-3-yl)-2-chloropyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 215 (( R )-1-(7-(1-Benzylpiperidin-3-yl)-2-chloropyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 216 ( S )-1-(4-((((7-(1-Benzylpiperidin-3-yl)-2-chloropyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one 217 ( R )-1-(4-((((7-(1-Benzylpiperidin-3-yl)-2-chloropyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one 218 4-((((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)piperidine-1-carboxamide 219 (7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methanamine 220 1-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -(((2 R ,6 S )-2,6-dimethyltetrahydro-2 H -pyran-4-yl)methyl)methanamine 221 (+/-)-1-(7-(( R/S )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((( R/S )-2,2-dimethyltetrahydro-2 H -pyran-4-yl)methyl)methanamine 222 (1-(7-(( R )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)- N -((( S )-2,2-dimethyltetrahydro-2 H -pyran-4-yl)methyl)methanamine 223 (1-(7-(( S )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)- N -((( R )-2,2-dimethyltetrahydro-2 H -pyran-4-yl)methyl)methanamine 224 (+/-)-( R/S )- N -((7-(( R/S )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-1-(tetrahydro-2 H -pyran-4-yl)ethan-1-amine 225 ( S )- N -((7-(( R )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-1-(tetrahydro-2 H -pyran-4-yl)ethan-1-amine 226 ( R )- N -((7-(( S )-1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-1-(tetrahydro-2 H -pyran-4-yl)ethan-1-amine 227 ( R )-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -(cyclopropylmethyl)- N -methylmethanamine 228 ( S )-1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5 -a ]pyrimidin-3-yl) -N- (cyclopropylmethyl) -N -methylmethanamine 229 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -(2,6-difluorobenzyl)- N -methylmethanamine 230 (4-((((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)(methyl)amino)methyl)phenyl)methanol 231 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -methyl- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 232 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)propan-2-amine 233 N -((7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)- N -(((2 R ,6 S )-2,6-dimethyltetrahydro-2 H -pyran-4-yl)methyl)propan-2-amine 234 1-(7-(1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5 -a ]pyrimidin-3-yl) -N- (cyclopropylmethyl) -N -methylmethanamine 235 N -((7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)-2,2,2-trifluoro- N -((tetrahydro-2 H -pyran-4-yl)methyl)ethan-1-amine 236 2-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5-a]pyrimidin-3-yl)-N,N-dimethylethan-1-amine 237 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2,6-dimethylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 238 1-(7-(1-(4-Chlorobenzyl)piperidin-3-yl)-2,5-dimethylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 239 ( S )-1-(7-(1-(2-Fluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 240 ( S )-1-(7-(1-(2,4-Difluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 241 ( S )-1-(7-(1-(3,5-Difluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 242 1-(7-(1-(4-Methoxybenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 243 ( R )-4-((((7-(( S) -1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)-1-methylpiperidin-2-one 244 ( S )-4-((((7-(( S) -1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)-1-methylpiperidin-2-one 245 ( R )-5-((((7-(( S )-1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)piperidin-2-one 246 ( S )-5-((((7-(( S )-1-Benzylpiperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)piperidin-2-one 247 ( S )-1-(4-((((7-(1-(3,4-Difluorobenzyl)piperidin-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)methyl)amino)methyl)piperidin-1-yl)ethan-1-one 248 1-(7-(1-Benzylpiperidin-3-yl)-2-methoxypyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine 249 7-((1-(4-Chlorobenzyl)piperidin-3-yl)methyl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 250 7-((1-(3-Chlorobenzyl)piperidin-3-yl)methyl)-2-methyl-3-(pyridin-4-yl)pyrazolo[1,5- a ]pyrimidine 251 1-(7-((1-(4-Chlorobenzyl)piperidin-3-yl)methyl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N , N -dimethylmethanamine 252 1-(7-((1-(3-Chlorobenzyl)piperidin-3-yl)methyl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N , N -dimethylmethanamine 253 1-(7-(1-(4-Chlorobenzyl)azepan-3-yl)-2-methylpyrazolo[1,5- a ]pyrimidin-3-yl)- N -((tetrahydro-2 H -pyran-4-yl)methyl)methanamine. 9. A method for producing a compound according to formula (I), said method comprising treating a compound of formula VI in which A is –(CR ₅ R ₅ ') _m -R ₄ , and Y is a halogen atom, a suitable boronic acid (or boronic acid ester) of formula VII, ; or said method comprises alkylating a compound of formula Ia in which A is hydrogen, , a suitable alkylating reagent of formula XI, where T is –(CR ₅ R ₅ ') _m -R ₄ , and Z is a leaving group; or alternatively by a reductive amination reaction using a suitable aldehyde of formula XI wherein Z is =O; and where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', X, m, n and t have the meanings defined in the previous paragraphs. 10. The method of claim 9, wherein Z is a leaving group representing iodine, bromine or chlorine. 11. A method for producing a compound according to formula (I), wherein R ₁ is –CH ₂ NR ₆ R ₆ ', said method comprising: carrying out a reaction of a compound of formula VI in which A is –(CR ₅ R ₅ ') _m -R ₄ , and Y is -COOH, with a suitable amine of formula IX, ; or carrying out a reaction of a compound of formula VI in which A is –(CR ₅ R ₅ ') _m -R ₄ , and Y is a halogen atom, with a suitable salt, which is potassium aminomethyl trifluoroborate, of formula X, ; or carrying out a reaction of a compound of formula VIII in which A is –(CR ₅ R ₅ ') _m -R ₄ , with a suitable amine of formula IX, ; or alkylation of a derivative of formula (Ib) in which A is hydrogen, a suitable alkylating reagent of formula XI, where T is –(CR ₅ R ₅ ') _m -R ₄ , and Z is a leaving group; or alternatively by a reductive amination reaction using a suitable aldehyde of formula XI wherein Z is =O; where R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ', R ₆ , R ₆ ', m, n and t have the meanings defined in the previous paragraphs. 12. The method of claim 10, wherein Z is a leaving group representing iodine, bromine or chlorine. 13. Use of compounds of formula (Ia), (Ib), (IIa), (IIb), (IIIa), (IIIb), (IV), (V), (VI), (VII), (VIII), (IX), (X) or (XI), , , , , , , , , , , , , , wherein R represents an alkyl group, Y represents hydrogen, a halogen atom or -COOH, A represents any of hydrogen, -C(R ₅ R _5' ) _m R ₄ or a protecting group for an amino functionality which is benzyl or tert -butoxycarbonyl, T represents a group -C(R ₅ R _5' ) _m R ₄ , and Z represents a halogen or an oxygen atom, and wherein R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ' , R ₆ , R ₆ ' , X, m, n and t have the meaning defined in the preceding paragraphs, to obtain compounds of formula (I). 14. Use of compounds of formula (Ia), (Ib), (VI) or (VIII), , , , , where Y is hydrogen, a halogen atom or -COOH, A is any of hydrogen, -C(R ₅ R _5' ) _m R ₄ or a protecting group for the amino functionality which is benzyl or tert -butoxycarbonyl, and where R ₁ , R ₂ , R ₃ , R ₄ , R ₅ , R ₅ ' , R ₆ , R ₆ ' , X, m, n and t have the meaning defined in the preceding paragraphs, to obtain compounds of formula (I). 15. A pharmaceutical composition having a bidirectional binding activity with the _α2δ -1 subunit of voltage-dependent calcium channels and with the sigma-1 (σ1) receptor, wherein the pharmaceutical composition contains an effective amount of a compound of formula (I) according to any one of claims 1-8 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier, excipient or carrier medium. 16. A compound of formula (I) according to any one of claims 1 to 8 for use as a medicinal product having bidirectional binding activity to the _α2δ -1 subunit of voltage-dependent calcium channels and to the σ1 receptor. 17. A compound of formula (I) according to any one of claims 1 to 8 for use as a medicinal product, preferably a medicinal product for the treatment of pain, in particular moderate to severe pain, visceral pain, chronic pain, cancer pain, migraine, inflammatory pain, acute pain or neuropathic pain, allodynia or hyperalgesia.