WO2015020565A1 - Substituted [1,2,4]triazolo[4,3-a]pyridines exhibiting antagonist properties to adenosine a2a receptors, and use thereof - Google Patents

Abstract

This invention relates to novel compounds - substituted [1,2,4]-triazolo[4,3-а]pyridines of general formula (I), or the pharmaceutically acceptable salts thereof, where A is an unsubstituted or substituted aminocarbonyl group -N-С(О)-, an acylamino group or aminocarbonyl; В is a non-aromatic cyclic substituent selected from С₄-С₆ cycloalkyl; an aromatic cyclic substituent selected from phenyl, which can be substituted by halogen, C₁-С₃ alkoxy; a non-aromatic 5-6 membered heterocyclic substituent with a nitrogen atom as the hetero atom, and possibly N-substituted C₁-С₃ alkyl; an aromatic 5-6 membered heterocyclic substituent in which the hetero atoms are selected from nitrogen, oxygen or sulphur, and which can be substituted by C₁-С₆ alkyl; or an aromatic 5-6 membered heterocyclic substituent in which the hetero atom is selected from nitrogen condensed with a benzene ring; R1a, R1b and R1c are independently Н, С₁-С₃ alkoxy. These compounds exhibit antagonistic activity in relation to adenosine A2A receptors. The invention also relates to the use of said compounds as an active component for pharmaceutical compositions, drugs and adjuvants. The invention also relates to methods for treating disorders in the function of the central nervous system (CNS) and neuro-degenerative, inflammatory, infectious and oncological diseases.

Description

 SUBSTITUTED [1,2,4] TRIAZOLO [4,3-A] PYRIDINES MANIFESTING THE PROPERTIES OF Adenosine A2A RECEPTOR ANTAGONISTS, AND THEIR

 APPLICATION

Technical field

 This invention relates to new compounds - substituted [1, 2,4] triazolo [4,3-a] pyridines exhibiting antagonistic activity against adenosine A2A receptors, and to their use as a drug substance, pharmaceutical compositions, drugs and Adyovants. The invention also relates to methods for treating disorders of the central nervous system (CNS), neurodegenerative, inflammatory, infectious and oncological diseases.

State of the art

 Adenosine regulates many physiological functions, in particular, acts as a cytoprotector in normal and pathophysiological conditions in response to stress in organs and tissues [Hasko G, Linden J, Cronstein B, Pacher P. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov. 2008; 7: 759-770]. This protective response can manifest itself as increased blood supply (vasodilation or angiogenesis), ischemic preconditioning [Akaiwa K., Akashi H, Harada H, Sakashita H, Hiromatsu S, Kapo T, Aoyagi S. Moderate cerebral venous congestion induces rapid cerebral protection via adenosine A l receptor activation. Brain Res. 2006; 1 122: 47-55], and / or anti-inflammatory effect (activation and infiltration of inflammatory cells, production of cytokines and free radicals) [Ohta A, Sitkovsky M. Role of G-protein-coupled adenosine receptors in downregulation of inflammation and protection from tissue damage. Nature. 2001; 41: 916-920]. Extracellular adenosine acts on receptors located on the cell membrane, activating the corresponding intracellular signaling cascades.

There are four subtypes of adenosine receptors, designated as Al, A2A, A2B, and A3 (Table 1), each of which has a unique pharmacological profile, tissue distribution, and binding to effector molecules [Fredholm BB, IJzerman AP, Jacobson KA, Klotz N, Linden J. International Union of Pharmacology. Xxv. Nomenclature and classification of adenosine receptors. Pharmacol Rev. 2001; 53: 527-552]. All adenosine receptors belong to the family of receptors associated with G-proteins (GPCRs), structurally resembling receptors for biogenic amines.

 Activation of A 1 receptors leads to inhibition of adenylate cyclase via receptor-bound A l Gi / o proteins [Londos C, Cooper DM, Wolff J. Subclasses of external adenosine receptors. PNAS USA. 1980; 77: 255 1 -2554], and also increases the activity of phospholipase C PLC [Rogel A, Bromberg Y, Sperling O, Zoref-Shani E. Phospholipase C is involved in the adenosine activated signal transduction pathway conferring protection against iodoacetic acid-induced injury in primary rat neuronal cultures. Neurosci Lett. 2005; 373: 218-221]. The receptors A l activate potassium channels, including KATP channels, and block the Q-, P- and типы-types of calcium Ca2 + channels.

 Activation of A2A receptors increases adenylate cyclase activity. In the peripheral system, the main proteins conjugated to A2A receptors are Gs proteins. In the striatum, where the content of A2A receptors is maximum, they are coupled with Golf proteins [Kull B, Svenningsson P, Fredholm BB. Adenosine A2A receptors are colocalized with and activate Golf in rat striatum. Mol Pharmacol. 2000; 58: 771-777], which, like Gs proteins, are associated with adenylate cyclase. A2A receptors are able to incorporate a PLC signaling cascade, induce inositol phosphate synthesis and increase intracellular calcium concentration, and also activate protein kinase C.

A2B receptors are positively associated with adenylate cyclase and phospholipase C. Many functions of A2B receptors are determined by phospholipase C. which is activated by Gq proteins [Linden J, Thai T, Figler H, Jin X, Robeva AS. Characterization of human A2B adenosine receptors: radioligand binding, western blotting, and coupling to Gq in human embryonic kidney 293 cells and HMC- 1 mast cells. Mol Pharmacol. 1 999: 56: 705-71 3]. These receptors are also involved in the signaling cascade of arachidonic acid [Donoso MV, Lopez R, Miranda R, Briones R, Huidobro-Toro JP. A2B adenosine receptor mediates human chorionic vasoconstriction and signals through the arachidonic acid cascade. Am J Physiol Heart Circ Physiol. 2005; 288: H2439-H2449]. Table 1. Properties of adenosine GPCR receptors

 Subtype

 A1 A2A A2B A3 receptors

 G-protein Gi, Go Gs, Golf Gs, Gq Gi, Gq

 Inhibition

 adenylate cyclases

 CAC)

 Activation

 Mechanism

 phospholipase C († AC) († AC) CAC) transmission

(† PLC) (| chCa ⁺² ) (TPLC) (TPLC) signals

 Blockade of calcium

channels (J.chCa ⁺² )

 Potassium activation

channels († chK ⁺ )

 Effector J, with AMP

 † cAMP † cAMP † cAMP molecule † IP3

† IP3 † IP3 † IP3 (secondary | chCa ⁺²

† chCa ⁺² † chCa ⁺² † chCa ² instant messengers) † chK ⁺

 Affinity

 adenosine to

 receptors 10 30> 100,000 1000

(radioliga vdno (rAl) (rA2A) (hA2B) (hA3) e binding ")

 Kd, PM

 Affinity

 adenosine to

 receptors 310 700 24000 290

(function (hAl) (hA2A) (hA2B) (hA3) testing ^b )

Таблица 1. EC50, PM

Table 1.

 a) [J Med Chem. 2000; 43: 2196]; b) [Bioorg Med Chem Lett. 201 1; 21 (7): 1933]

A3 receptors are involved in classical signaling pathways, inhibiting adenylate cyclase, stimulating phospholipase C, and causing mobilization of calcium ions [Z ou QY, et al. Molecular cloning and characterization of an adenosine receptor: the A3 adenosine receptor. PNAS USA. 1992; 89: 7432-7436]. A3 receptor agonists inhibit melanoma cell growth by participating in the WNT signaling cascade [Fishman P, et al. Evidence for involvement of Wnt signaling pathway in IB-MECA mediated suppression of melanoma cells. Oncogene. 2002; 21: 4060-4064].

Small molecules - modulators of adenosine receptors can be widely used in pharmacology and medicine. Currently, a large number of substances with affinity for adenosine receptors are known, but most of them are not selective. Non-selective ligands of adenosine receptors (for example, some analogues of adenine and xanthines) have a very complex pharmacological profile, and therefore have extremely limited clinical use (with the exception of non-selective weakly affinity caffeine). Therefore, the search for selective adenosine ligands is an urgent task. Of particular importance are selective A2A receptor antagonists. A large number of scientific papers and patents are devoted to the use of A2A receptor antagonists as drug candidates for the treatment of central nervous system diseases, which include, but are not limited to:

 - Parkinson's disease [Pinna A. Novel investigational adenosine A2A receptor antagonists for Parkinson's disease. Expert Opin I nvest Drugs. 2009; 1 8 (1 1): 1 619-163 1];

 - Alzheimer's disease and other cognitive impairment [Takahashi RN, Pamlona FA, Prediger RD. Adenosine receptor antagonists for cognitive dysfunction: a review of animal studies. Front Biosci. 2008; 13: 2614-32];

 - cerebral ischemia and stroke [Monopoli A, Lozza G, Foriani A, Mattavelli A, Ongini E. Blockade of adenosine A2A receptors by SCH 58261 results in neuroprotective effects in cerebral ischaemia in rats. Neuroreport. 1998; 9 (17): 3955-3959];

 - mental disorders [Wardas J. Potential role of adenosine A2A receptors in the treatment of schizophrenia. Front Biosci., 2008; 13: 4071-4096];

 - other neurodegenerative diseases and addictions [Ribeiro JA, Sebastiao AM, de Mendonca A. Adenosine receptors in the nervous system: pathophysiological implications. Prog Neurobiol. 2002; 68 (6): 377-392].

The prospect of searching for selective adenosia A2A ligands is supported by a series of CNS drug candidates that are currently at different stages of clinical trials (Table 2) [http://www.integrity.prous.com]:

Table 2. A2A antagonists of adenosine receptors at different stages of testing

It was previously shown that adenosine, which accumulates near tumor tissue [Blay J, White TD, Oskin DW. The Extracellular Fluid of Solid Carcinomas Contains immunosuppressive Concentrations of Adenosine. Cancer Research. 1997; 57: 2602-2605], significantly inhibits the ability of activated T-lymphocytes and natural killer cells to bind to and kill tumor cells [Hoskin DW, Reynolds T, Blay J. Adenosine as a possible inhibitor of killer T-cell activation in the microenvironment of solid tumours. Int J Cancer. 1994; 59: 854-855]. Hypoxia, developing in conditions of solid tumors, leads to an increase in the concentration of adenosine near the tumor tissue. Adenosine, by binding to type A2A adenosine receptors located on the cell membrane of lymphocytes, transmits an adenosine signal into cells, which reduces the ability of lymphocytes to attack tumor tissue [Sitkovsky MV, Kjaergaard J, Lukashev D, Ohta A. Hypoxia-Adenosinergic Tumor Immunosuppression Tum: Regulatory Cells and Cancerous Tissue Hypoxia. Clin Cancer Res. 2008; 14 (19): 5947-5952]. On this basis, a new approach has been proposed to enhance the effectiveness of antitumor therapy (in particular, vaccines) using an adjuvant that is an antagonist of A2A receptors [Ohta A, Sitkovsky M. Methods and composition for improving immune responses. WO 2008/147482 04.12.2008].

Studies have shown that agonists of A2A adenosine receptors are important regulators of inflammatory processes. A2A agonists have been shown to have anti-inflammatory properties in vitro and in vivo. Adenosine, interacting with the surface receptors AI, A2A, A2B, and A3, has a different biological effect. Of all four receptors, A2A is the most common and closely associated with the inflammatory response. The studies revealed the ability of A2A to inhibit the phosphorylation of Zap-70 tyrosine kinase, the secretion of eosinophils and monocytes, weaken the perforin and cytotoxicity of lymphokine-activated killer cells. Activation of the A2A adenosine receptor suppresses the inflammatory signaling system in cytokines and accelerates the healing process. [M.A. Trevethick, SJ Mantell, EFStuart, A. Barnard, I .N. Wright, M Yeadon, Pfizer Global R&D, “Treatment of inflammation of the respiratory tract with adenosine A2A receptor agonists,” Journal of the Pharmacist, 2009, issue N ^” 3, http://www.provisor.com.ua /] Thus, the search for effective and selective A2A receptor antagonists seems to be an extremely important and promising task.

 In order to develop new highly effective A2A ligands, the authors of this invention performed a wide screening of a variety of low molecular weight compounds, determining the effectiveness of their interaction with adenosine receptors and. Surprisingly, hit compounds were discovered, which are some derivatives of [1, 2,4] triazolo [4,3-a] pyridines. Then, directed modifications of the detected structures and testing of new compounds were carried out; in this case, the structure – activity relationship was established and the most promising series and leader compounds were selected. As a result, a series of new derivatives of [1, 2,4] triazolo [4,3-a] pyridines, previously not described in the literature, which are original and highly effective A2A receptor antagonists, was synthesized.

 An object of the present invention is to provide novel selective A2A receptor antagonists.

 This goal is achieved by new antagonists of adenosine A2A receptors, which are substituted [1, 2,4] triazolo- [4,3-a] pyridines of the general formula I, as well as their pharmaceutically acceptable salts.

 The subject of the present invention is substituted [1, 2,4] triazolo | 4,3-a] pyridines of the general formula I, as well as their pharmaceutically acceptable salts:

 I

wherein A is not necessarily a substituted aminocarbonyl group -NC (O) -, wherein the amino group may be substituted and the substituents may be selected from hydrogen, SrSgal yl, optionally substituted Ci-Szalkoksi, _Cs-C6 cycloalkyl, 5-6- membered heteroaryl in which the heteroatoms are selected from oxygen or nitrogen; an aryl selected from phenyl, optionally substituted with hydroxy, C hC ^ alkyl. With 1-C5 alkoxy, halogen, CrCgacylamino group, or naphthyl;

or an amino group is selected from _Cs-C7 heterocyclyl having 1 -2 goma geteroa loop selected from nitrogen, oxygen or sulfur, optionally substituted by hydroxy, Q - Szalkilom, benzyl, phenyl which may be substituted with halogen, and wherein said heterocyclyl may be condensed with a benzene ring;

 an acylamino group in which the acyl is selected from

C) -C ₆ alkylcarbonyl, wherein the alkyl may be substituted by phenyl, substituted phenyl wherein the substituents are selected from the CDS _b alkoxy; A 5-membered heteroaryl with a heteroatom selected from an oxygen or sulfur atom;

benzoyl, possibly substituted by CpC _b alkyl, C | -C ₅ alkoxy, C hC ₅ alkylthio or halogen, methylenedioxy;

 heterocyclylcarbonyl, in which heterocyclyl is selected from a 5-6 membered heterocyclyl, with 1 to 2 heteroatoms selected from nitrogen, oxygen or sulfur, optionally fused to a benzene ring and optionally substituted with Ci-C 1 -alkyl, halogen;

 or a ureido group in which one of the substituents on the terminal amido group is hydrogen, and the second substituent is selected from:

 Cj-Szalkyl substituted with phenyl, a 5-membered saturated or aromatic heterocyclyl, in which the heteroatoms are selected from oxygen or sulfur;

C ₂ -C _b alkenyl;

aryl selected from phenyl, substituted _C1-C5 alkyl, Ci-Szalkoksi, ethylenedioxy, methylenedioxy, halogen, Ci -Szalkilkarbonilom;

 A 5 membered heterocyclyl in which the heteroatoms are selected from a sulfur or oxygen atom, and optionally substituted with an alkyloxycarbonyl group;

B is a non-aromatic cyclic substituent selected from C - C ₆ cycloalkyl;

an aromatic cyclic substituent selected from phenyl which may be substituted with halogen, CpSalkalkoxy; a non-aromatic 5-6 membered heterocyclic substituent with a nitrogen atom as a heteroatom, and optionally Ν-substituted with C | -C ₃ alkyl;

aromatic 5-6 membered heterocyclic substituent in which the heteroatom is selected from nitrogen, oxygen or sulfur, and which may be substituted With | -C ₆ alkyl;

 or an aromatic 5-6 membered heterocyclic substituent in which the heteroatom is selected from nitrogen condensed with a benzene ring;

Rla, Rib and Rlc independently represent hydrogen, C iC ₃ alkoxy;

 excluding the compounds shown in Table 3.

Раскрытие изобретения

Disclosure of invention

 The following are definitions of terms that are used in the description of the present invention /

“Aminocarbonyl” means a —C (= 0) NR ₂ group, each R independently of one another is hydrogen, alkyl, alkenyl (see substituents of the aminocarbonyl group, see “carbamoyl substituent”). Preferably carbamoyl, methylamocarbonyl, ethylaminocarbonyl, propylaminocarbonyl or butylaminocarbonyl. Aminocarbonyl may have substituents, see "carbamoyl substituent" as defined in this section.

“Aminothiocarbonyl” means RC (= S) NH ₂ , aminothiocarbonyl may have substituents, see “carbamoyl substituent”, “substituted aminothiocarbonyl group” as defined in this section.

 "Substituted aminothiocarbonyl group" (aminothiocarbonyl) means R'R "N-C (= S) is a group in which the substituents R 'and R" may be optionally substituted with alkyl, cycloalkyl, aryl, hetaryl and heterocyclyl, the value of which is defined in this section. Preferred aminocarbonyl groups are optionally substituted CrCalkyl, C | -C5 cycloalkyl, optionally substituted aryl (see substituent of the cyclic system), optionally substituted hetaryl (see substituent of the cyclic system), optionally substituted heterocyclyl (see substituent of heterocyclyl) or amino group R'R "N.

“Amino group” means a radical of the formula —NR ₂ in which each R independently of one another is hydrogen, alkyl, alkenyl or cycloalkyl, for example, —NH ₂ , methylamino, diethylamino, cyclohexylamino, tert-butyl pshino or ethylamino.

“Azaheterocycle” means an aromatic or non-aromatic monocyclic or polycyclic system containing at least one nitrogen atom in a ring. Preferably piperidine, piperazine, pyrrolidine, morpholine, thiomorpholine, azacyclooctane. The azaheterocycle may have substituents (see cyclic system substituents).

“Aryl” means an aromatic monocyclic or polycyclic system comprising from 6 to 14 carbon atoms, preferably from 6 to 10 carbon atoms. Aryl may contain one or more “cyclic system substituents” which may be the same or different. Preferably phenyl or naphthyl.

 "Alkenyl" means a linear or branched hydrocarbon group containing from 2 to 7 carbon atoms and including at least one carbon-carbon double bond.

 Branched means that one or more lower alkyl groups, such as methyl, ethyl or propyl, are attached to the linear alkenyl chain. Preferred and alkenyl groups are ethenyl, propenyl, n-butenyl, isobutenyl, 3-methylbut-2-enyl, n-pentenyl, and cyclohexylbutenyl.

 An alkenyl group may have one or more substituents, see “Alkenyl Substituents”.

 "Alkenyl group substituents" may be halogen, alkenyloxy, cycloalkyl, cyano, hydroxy, alkoxy, carboxy, alkynyloxy, aralkoxy, aryloxy, aryloxycarbonyl, alkylthio, heteroaralkyloxy, heterocycle il, heterocyclylalkyloxy, alkoxycarbonylcarbonyl.

 "Alkynyl" means a linear or branched hydrocarbon group containing from 2 to 12 carbon atoms and including at least one carbon-carbon triple bond.

 Branched means that one or more lower alkyl groups, such as methyl, ethyl or propyl, are attached to the linear alkynyl chain. An alkynyl group may have one or more substituents, see “Alkenyl Substituents”. Preferred alkynyl groups are ethynyl, propynyl, n-butyl, isobutynyl, 3-methylbut-2-ynyl, n-pentynyl, buta-1, 3-diine and hexa-1, 3,5-triine.

"Alkyl" means an aliphatic hydrocarbon linear or branched group with 1 to 6 carbon atoms in the chain. A branched group means that the group C | —C _b alkyl, such as methyl, ethyl or propyl, is attached to the alkyl linear chain. Preferred straight or branched alkyl groups are those representing alkyl groups having from 1 to 10 carbon atoms. Most preferred lower alkyl groups have from 1 to 8 carbon atoms. Preferred alkyl groups are C | -C ₆ alkyl, more methyl, ethyl, n-propyl, 2-iso-propyl, n-butyl are preferred. iso-butyl, sec-butyl, tert-butyl, cyclopropylmethyl, cyclobutylmethyl, cyclopentylmethyl, n-pentyl, 2-pentyl, 3-pentyl, neo-pentyl, n-hexyl. Alkyl may have substituents, see "Substituted alkyl."

 "Alkylcycloalyl" means cycloalkyl substituted with alkyl. Preferably 4-, 2-, 3- or 4-methyl or ethylcyclohexyl.

 “Alkylcycloalkylalkyl” means alkyl substituted with alkylcycloalkyl.

Preferably 2-, 3- or 4-methyl- or ethylcyclohexylmethyl or 2-, 3- or 4-methyl- or ethylcyclohexylethyl.

 “Aralkyl” means alkyl substituted with aryl. Preferred aralkyl groups include benzyl, naphth-1-ylmethyl, naphth-2-ylmethyl and phenethyl.

 “Alkyloxy” or “Alkoxy” means a Ci-Sat Alkyl O- group in which alkyl is defined in this section. Preferred alkoxy groups are methoxy, ethoxy, i-propoxy, iso-propoxy, n-butoxy and tert-butoxy.

 “Aromatic cycle” (aromatic system) means a planar cyclic system in which all atoms of the cycle participate in the formation of a single conjugation system, which, according to the Hückel rule, includes (4n + 2) π-electros (n is a non-negative integer). Examples of aromatic cycles are benzene, naphthalene, anthracene, and the like. In the case of “heteroaromatic cycles”, π-electrons and p-electrons of heteroatoms participate in the conjugation system; their total number is also equal to (4n + 2). Examples of such cycles are pyridine, thiophene, pyrrole, furan, thiazole and the like. An aromatic ring may have one or more “ring system substituents” and may be anelated with a non-aromatic ring, heteroaromatic or heterocyclic ring.

“Acyl group” (Acyl) means RC (= 0) -, (preferably CgC ₆ acyl) optionally substituted with C | -C5alkyl-C (= 0) -, C | -C5 cycloalkyl-C (= 0) -, (preferably cyclopropyl-C (= 0) -, cyclobutyl-C (= 0) -); heterocyclyl-C (= 0) -, (preferably 2-methylfuran), aryl-C (= 0) - (aroyl), aralkyl-C (= 0) -, (preferably 3-phenylpentai-C (= 0) -) , heteroaryl-C (= 0) - (heteroaroyl), heteroarylalkyl-C (= 0) - group in which SrSzalkil-, _b CDS al enyl, SrSztsikloalkil-, getertsiklil-, aryl, aralkyl, heteroaryl, heteroarylalkyl, methoxy group, these groups may have substituents, see “Cyclic system substituents”, “substituted alkyl”, “substituted alkenyl”, “heterocyclic system substituents” as defined in this section.

R² _k+2, где R~_k, R _k+i и R _k+2 могут принимать значение водород, С|-С₅алкил-, арил, насыщенный или ненасыщенный гетероциклил, или NR² _kR² _k+2 представляет собой 5-6 членный гетероцикл, указанные группы могут иметь заместители, см. «заместители циклической системы» , «замещенный алкил», «заместители гетероциклической системы», «замещенный арил», определенные в данном разделе. “Α-aminoacyl group” (α-aminoacyl) means

R ² _{k + 2} , where R ~ _k , R _{k +} i and R _{k + 2} can be hydrogen, C | -C ₅ alkyl-, aryl, saturated or unsaturated heterocyclyl, or NR ² _k R ² _{k + 2} is 5-6 membered heterocycle, these groups may have substituents, see “cyclic system substituents”, “substituted alkyl”, “heterocyclic system substituents”, “substituted aryl” defined in this section.

“Acylo sigroup” means an R (= 0) -0 group

“Hydrazinocarbonyl group” means a —C (= 0) —NH — NH ₂ group.

 The hydrazinocarbonyl group may have substituents, see “carbamoyl substituent” as defined in this section.

 “Heteroaryl” (hetaryl) means an aromatic monocyclic or polycyclic system comprising from 5 to 14 carbon atoms, preferably from 5 to 10, in which one or more carbon atoms are replaced by a heteroatom or heteroatom and, such as nitrogen, sulfur or oxygen. The prefix "aza", "oxa" or "thia" before "heteroaryl" means the presence in the cyclic system of a nitrogen atom, an oxygen atom or a sulfur atom, respectively. The nitrogen atom in the heteroaryl can be oxidized to the Ν-oxide. Heteroaryl may have one or more “ring system substituents”, which may be the same or different. Preferably pyrrolyl, furanyl, thienyl, pyridinyl. Heteroaryl may have substituents (see cyclic system substituents).

“Heterocycle” means an aromatic or non-aromatic saturated or partially saturated monocyclic or polycyclic system comprising from 3 to 10 carbon atoms, preferably from 4 to 6 carbon atoms, in which one or more carbon atoms are replaced by a hetero atom such as nitrogen, oxygen, sulfur, phosphorus. The prefix "aza", "oxa" or "thia" before heterocyclyl means the presence in the cyclic system of a nitrogen atom, an oxygen atom or a sulfur atom, respectively. Heterocyclyl may have one or more substituents, which may be the same or different. The nitrogen and sulfur atoms in the heterocyclyl can be oxidized to Ν-oxide, S- oxide or S-dioxide. Representative heterocyclyls are piperidiyl, pyrrolidinyl, piperazinyl, morpholinyl, thiomorpholinyl, thiazolidinyl, 1, 4-dioxan-2-yl, tetrahydrofuryl, tetrahydrothienyl, etc. Heterocyclyl may have substituents. Compounds are preferred: piperidinyl substituted with methyl; piperidinyl substituted with an optionally substituted hydroxy group; piperidinyl substituted with phenyl; piperazinyl substituted with CpSalkyl.

“Hydro-group” (Hydro-strong group) means —OH group.

“Halogen” means fluoro, chloro, bromo and iodo. Fluorine, chlorine are preferred. “Cycloalkyl” means a saturated carbocyclic group having one or more rings having 3-10 carbon atoms. Preferred cycloalkyl groups include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and decahydronaphthyl.

 “Cycloalkylalkyl” means an alkyl group substituted with a cycloalkyl group. Preferred cycloalkylalkyls include cyclopentylmethyl,

cyclohexylmethyl, cyclohexylethyl, decahydronaphth-1-methylmethyl and decahydronaphth-2-ylmethyl. “Cyano group” means the group —C = N.

 “Substituted alkyl” substituted alkyl may have one or more, same or different substituents, including halogen, alkenyloxy, cycloalkyl, aryl, heteroaryl, heterocyclyl, hydroxy. Preferred alkyl substituents are: acyl, acylamino, acyloxy, alkenyl, alkoxy, alkyl, alkynyl, amino, aryl, aryloxy, carbamoyl, carboalkoxy, carboxy, carboxyamido, carboxyamino, cyano, disubstituted amino, formyl, guanidino, halo, halo, , hydroxy, iminoamino, nitro, oxo, phosphonamine, sulfinyl, sulfonamine, sulfonyl, thio, thioacylamine, thioureido or ureido.

“Substituted aryl” means phenyl or naphthyl substituted with one or more substituents of the aryl group, which may be the same or different, where the “substituent of the aryl group” includes alkyl, alkenyl, alkynyl, aryl, aralkyl, hydroxy group, alkoxy group, aryloxy group, aralkoxy group , hydroxyalkyl, acyl, formyl, carboxy group, alkenoyl, aroyl, halogen, nitro group, trihaloimethyl, cyano group, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl, acylamino group, aroylamino, carbamoyl, alkylcarbamoyl, dialkylcarbamoyl, arylcarbamoyl, aralkilkarbamoil, alkylsulfonyl, alkylsulfinyl, arylsulfonyl, arylsulfinyl, aralkylsulfonyl, aralkylsulfinyl, or - NR _a R _b, where R _a and R _b are independently hydrogen, alkyl, aryl or aralkyl.

Preferably phenyl substituted with hydroxy; C ₁ -C ₅ alkyl (preferably methyl); halogen (preferably chlorine, fluorine); aminocarbonyl group; sulfo group. Preferably, naphthyl substituted with C ₁ -C ₅ alkyl. Aryl can be anelated with a non-aromatic ring system or heterocycle.

"Amino group substituents" amino group substituents R 'and R "are hydrogen, optionally substituted with C] -C ₅ a kil, optionally substituted with C3 - Czcycloalkyl (see the Deputy of the cyclic system), optionally substituted aryl (see the Deputy of the cyclic system), optionally substituted heteroaryl (see cyclic system substituent), optionally substituted heterocyclyl (see cyclic system substituent), alkoxycarbonyl substituted by linear or non-linear C | - C ₅ alkyl, halogen, heterocyclyl; alkylaminocarbonyl, arylaminocarbonyl, heteroarylaminocarbonyl, heterocyclylaminocarbonyl.

"Substituents of the cyclic system" may be representatives of aryl groups, preferably phenyl or naphthyl, substituted phenyl or substituted naphthyl. Preferably phenyl substituted with hydroxy; C ₁ -C ₅ alkyl; halogen; aminocarbonyl group.

Aryl can be annelated with a non-aromatic ring system or heterocycle. Preferably, the cyclic system moieties are hydrogen, halogens (chlorine, fluorine, bromine), optionally substituted With Csalkyl, hydroxy-group, With | - C ₅ alkyloxy group (methoxy, ethoxy, propoxy), carboxy group, aminocarbonyl (see "aminocarbonyl"), phenyl annelated with a 5-7 membered saturated ring containing 1-3 heteroatoms (nitrogen, oxygen and sulfur atoms are preferred).

“Substituent” means a chemical radical that is attached to a molecular skeleton (scaffold, fragment), for example, “substituent alkyl”, “substituent of amino group”, “substituent of carbamoyl”, “substituent of cyclic system”, the meanings of which are defined in this section. "Substituted aminocarbonyl group" (aminocarbonyl) means R'R "NC (= 0) - a group in which the substituents R 'and R" may be optionally substituted by alkyl, cycloalkyl, aryl, hetaryl and heterocyclyl, the meanings of which are defined in this section . Preferred aminocarbonyl groups are optionally substituted Ci-Csalkyl, C | -C ₅ cycloalkyl, optionally substituted aryl (see substituent of the cyclic system), optionally substituted hetaryl (see substituent of the cyclic system), optionally substituted heterocyclyl (see substituent of heterocyclyl) or amino group R'R "N.

аннелироваиный гетероарилциклоалкенил, аннелированныи гетероарилциклоалкил, аннелироваиный гетероарилгетероцикленил, аннелироваиный гетероарил гетероциклил, аннелироваиный арилциклоалкенил, аннелироваиный арилциклоалкил, аннелированныи арилгетероциклеиил, аннелированныи арилгетероциклил. Предпочтительными «заместителями карбамоильиым и» являются алкил, циклоалкил, арил, гетероарил, гетероциклил, алкоксикарбонилалкил, аралкоксикарбонилалкил, гетероаралкилокси-карбонилалкил или R_k ^aR_k+i^aN-, R_k ^aR_k+ι^aNC(=0)-aлκил, аннелироваиный арилгетероциклеиил, аннелироваиный арилгетероциклил. “Arbamoyl substituent” means a substituent attached to an aminocarbonyl group, the meaning of which is defined in this section. The carbamoyl substituent is hydrogen, alkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, heteroaralkyloxycarbonylalkyl or R _k ^a R _{k +} i ^a N-,

annelirovainy heteroarylcycloalkenyl, annelirovannyi heteroarylcycloalkyl, heteroarylheterocyclenyl annelirovainy, annelirovainy heteroaryl, heterocyclyl, annelirovainy arylcycloalkenyl, arylcycloalkyl annelirovainy, annelirovannyi arilgeterotsikleiil, annelirovannyi arylheterocyclyl. Preferred "carbamoyl substituents and" are alkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, alkoxycarbonylalkyl, aralkoxycarbonylalkyl, heteroaralkyloxycarbonylalkyl or R _k ^a R _{k +} i ^a N-, R _k ^a R _{k +} ι ^a NC (= 0) -a anneliroin arylheterocyclyl, anneliroin arylheterocyclyl.

“Heterocycle substituents” may be representatives of aryl groups, preferably phenyl or naphthyl, substituted phenyl or substituted naphthyl. Aryl can be anelated with a non-aromatic ring system or heterocycle. Preferred cyclic system moieties are hydrogen, halogens (chlorine, fluorine, bromine), optionally substituted CgSalkyl, optionally substituted cycloC Czalkyl, C ₁₃ -C ₅ alkene, hydroxy-group, C ₁ -C ₅ alkyloxy group (methoxy, ethoxy, propoxy), cyano, CpSalkyloxycarbonyl (methyl, ethyl), alkylthio group (methylthio), carboxy group, aminocarbonyl (see "am inocarbonyl"), phenyl anelated with 5-7th- a saturated saturated ring containing 1 to 3 heteroatoms (nitrogen, oxygen and sulfur atoms are preferred).

 “Medicinal product (preparation)” - a substance (or a mixture of substances in the form of a pharmaceutical composition) in the form of tablets, capsules, injections, ointments and other formulations intended to restore, correct or alter physiological functions in humans and animals, as well as for treatment and disease prevention, diagnosis, anesthesia, contraception, cosmetology and more.

"Nitro group" means a group - O2.

“Trifluoromethyl” means a —CF3 group;

"Ureido" means the group NH2 — CO — H—.

 More preferred are substituted [1, 2,4] triazolo [4.3-a] pyridines represented by the general formulas 1-1, 1-2, 1-3, and their pharmaceutically acceptable with

where: B has the meanings defined above;

R2a, R2b and R2c independently represent H, C1-C3 alkoxy; R3a and R3b independently represent hydrogen, C 1 -C 5 alkyl, optionally substituted with C i-Szalkoxy, C ₃ -C ₆ cycloalkyl, 5-6 membered heteroaryl, in which the heroatoms are selected from oxygen or nitrogen; aryl selected from phenyl optionally substituted with hydroxy, C | -C5a keel, C i - C5 alkoxy, halogen, C | -C5 acylam of a foreign group, or naphthalene;

R3a and R3b may together form cyclic substituents, wherein the group R3a-N-R3b represents a C ₃ -C ₇ heterocyclyl containing 1 -2 heteroatoms in the ring selected from nitrogen, oxygen or sulfur, optionally substituted with hydroxy, C | -Zalkyl, benzyl, phenyl, which may be substituted by halogen, wherein said heterocyclyl may be fused to a benzene ring;

R4 is C 1 -C5 a kil, where alkyl may be substituted with phenyl, substituted with phenyl, in which the substituents are selected from CpSalkalkoxy; A 5-membered heteroaryl with a heteroatom selected from an oxygen or sulfur atom; aryl selected from phenyl optionally substituted with Ci-Szalkyl, C ^ Szalkalkoxy, C gSzal ylthio or halogen, methylenedioxy; heterocyclyl, in which heterocyclyl is selected from a 5-membered heterocyclyl, with 1 to 2 heteroatoms selected from nitrogen, oxygen or sulfur, possibly fused with a benzene ring and optionally substituted with C 1 -C ₅ alkyl, halogen;

 R5 is hydrogen;

R6a and R6b independently represent hydrogen, C 1 -C3 alkyl substituted with phenyl, a 5-membered saturated or aromatic heterocyclyl, in which the heteroatoms are selected from oxygen or sulfur; C ₂ -C ₆ alkenyl, aryl selected from phenyl, substituted CDS _b alkyl, C ^ Szalkoksi, ethylenedioxy, methylenedioxy, halogen, C _\ - C ₃ alkylcarbonyl;

 R6a and R6b may together form cyclic substituents, wherein the R6a-N-R6b group is a 5 membered heterocycle in which the heteroatoms are selected from a sulfur or oxygen atom, and optionally substituted with an alkyloxycarbonyl group;

The most preferred derivatives of [1, 2,4] triazolo [4,3-a] pyridines are: 3- (4-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3- methoxyphenylamide (1-1-01);

 3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-methoxyphenylamide (1-1-02);

 3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid naphthyl-1-amide (1-1-03);

 3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-methylphenylamide (1-1-04);

3- (4-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-methylphenylamide (1-1-05); 3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid feilamide (I-1-06);

 3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-propylamide (1-1-07);

 3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 4-methylphenylamide (1-1-08);

 3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 4-fluorophenylamide (1-1-09);

 3- (4-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid (2-methoxyphenyl) ethylamide (1-1-10);

 3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid (2-methoxyphenyl) methylamide (1-1-11);

 3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-fluorophenylamide (1-1-12);

 3- (4-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-chlorophenylamide (1-1-13);

 3- (4-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-chlorophenylamide (1-1-14);

 3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-chlorophenylamide (1-1-15);

 3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methylphenylamide (1-1-16);

 3- (4-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methylphenylamide (1-1-17);

 3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-hydroxy-6-methylphenylamide (1-1-19);

 3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridi11-8-carboxylic acid

(cyclohexyl) methylamide (1-1-20);

3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2,3-dimethylphenylamide (1-1-21); 3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3,4-dimethylphenylamide (1-1-23);

 3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3,5-dimethylphenyl id (1-1-24);

 3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-ethylphenylamide (1-1-25);

 3- (pyrid-4-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 3-methylphenylamide (1-1-26);

 3- (pyrid-4-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-methylphenylamide (1-1-27);

 3- (pyrid-3-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-methylphenylamide (1-1-28);

 3- (pyrid-3-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-methoxyphenylamide (1-1-29);

 3- (5-methylfuryl-2) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methoxyphenylamide (1-1-30);

 3- (thienyl-2) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methoxyphenyl id (1-1-31);

 3- (indol-2-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-methoxyphenylamide (1-1-32);

 3 - ^ - methylpiperidin-4-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-ethylphenylamide (1-1-33);

 3 - ^ - methylpiperidin-4-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-methoxyphenylamide (1-1-34);

 3-cyclobutyl- [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methoxyphenylamide (1-1-35);

 3- (4-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid (furan-2-yl) methylamide (1-1-36);

3- (2-fluorophenyl) - [1, 2,4] triazolo | 4,3-a] pyridin-8-carboxylic acid (furan-2-yl) methylamide (1-1-37); 3- (4-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid heptamethyleneamide (1-1-38);

 - {3- (4-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carbonyl} -3,5-dimethylpiperidine (1-1-39);

 - {3- (4-methyphenyl) - [l, 2,4] thiazole [4,3-a] pyridine-8-aponyl} -4-hydroxy-4- (4-chlorophenyl) -piperidine (1-1 -40);

 - {3- (4-φτophenyl) - [l, 2,4] τ -razole [4,3-a] RIiridi n-8-aponyl} -4-benzylpyperidine (1-1-41);

 - {3- (4-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carbonyl} -1, 2,3,4-tetrahydroquinoline (1-1-42);

 - {3- (4-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carbonyl} -4-hydroxy-4- (4-chlorophenyl) piperidine (1-1- 43);

 3-phenyl- [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methyl4-chlorophenylamide (1-1-44)

 3- (4-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-naphthylamide (1-1-47);

 3- (4-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-propylamide (1-1-48);

 3- (2-methoxyphenyl) -5-methoxy- [1, 2,4] triazolo [4,3-a] pyridine-8-carboic acid

2-methylphenylamide (1-1-49);

 3- (2-methoxyphenyl) -5-methoxy- | 1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid

2-fluorophenylamide (1-1-50);

 3- (2-methoxyphenyl) -5-methoxy- [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-methylphenylamide (1-1-51);

 3- (2-fluorophenyl) -5-ethoxy- [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid (furan-2-yl) methylamide (1-1-52);

 - {3- (2-methoxypheyl) -5-methoxy- [1, 2,4] triazolo [4,3-a] pyridin-8-carbooyl} -piperazine (1-1-53);

- {3- (2-methoxyphenyl) -5-methoxy- [1, 2,4] triazolo [4,3-a] pyridin-8-carbonyl} ^ '- methylpiperazine (1-1-54); M- {3- (2-methoxyphenyl) -5-metho- [1,2,4] triazolo [4,3-a] pyridin-8-carbonyl} -2-hydroxyethylamine (1-1-55);

 8 - [(2-ethoxybenzoyl) amino] -3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-01); 8 - {[(2-methoxyphenyl) acetyl] amino} -3-cyclobutyl- [1, 2,4] triazolo [4,3-a] pyridine (I-2-02);

 8 - [(thien-3-yl) acetylamino] -3-cy lobutyl- [1, 2,4] triazolo [4,3-a] pyridine (1-2-03);

8 - [(2-chloro-5-1methylthio-benzoyl) amino] -3-cy lobutyl- [1,2,4] triazolo [4,3-a] pyridime

(1-2-04);

 8 - [(thien-3-yl) carbonylamino] -3-cyclobutyl- [1, 2,4] triazolo [4,3-a] pyridine (1-2-05);

8 - [(3-methylthien-2-yl) carbonylamino] -3-cy lobutyl- [1,2,4] triazolo [4,3-a] pyridine

(1-2-06);

 8 - [(indol-2-yl) carbonylamino] -3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-07); 8 - [(3-fluoro-4-metho-si-benzoyl) amino] -3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-08);

 8 - [(2,3-dihydrobenzo [1,4] dio-syn-2-yl) carbonylamino] -3-cy lobutyl- [1, 2,4] triazolo [4,3-a] pyridine (1-2- 09);

 8 - [(5-chlorothien-2-yl) arbonylamino] -3-cy lobutyl- [1,2,4] triazolo [4,3-a] pyridine (I-2-U);

 8 - [(3,4-methylenedioxybenzoyl) amino] -3-cyclobutyl- [1, 2, 4] triazolo | 4,3-a | pyridine (1-2-11);

 8 - [(5-methylisoxazol-3-yl) carbonylamino] -3-cyclobutyl- [1, 2,4] triazolo | 4,3-a] pyridine (1-2-12);

 8 - [(2-metho-sibenzoyl) amino] -3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-13); 8 - [(2-metho-sibenzoyl) amino] -3-cyclopentyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-14); 8 - [(2 is sibenzoyl) amino] -3-cy lopentyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-15); 8 - [(2-methoxybenzoyl) amino] -3-cyclo-sil- [1,2,4] triazolo [4,3-a] pyridine (1-2-16); 8 - [(2-metho-sibenzoyl) amino] -3- (Y-methylpiperidin-4-yl) - [1,2,4] griazolo [4,3-a] pyridine (1-2-17);

8- (benzoylamino] -3- (Y-methylpiperidin-4-yl) - [1, 2,4] triazolo [4,3-a] pyridine (1-2-18); 8- (benzoylamino] -3- (2-methoxyphenyl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-19);

8- (2-eto sibenzoylamino] -3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine (1-2-20);

 8- (2-ethoxybenzoylamino] -3-phenyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-21);

8 - [(2-fluorobenzoyl) amino] -3- (T-methylpiperidin-4-yl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-22);

 8 - [(2-fluorobenzoyl) amino] -3- (methylpiperidin-3-yl) - [l, 2,4] τ-trizole [4,3-a | pyridine (1-2-23);

 8 - [(2-ethoxybenzoyl) amino] -3- (Thl-ethylpiperidin-3-yl) - [1, 2,4 | triazolo | 4.3-a] pyridine (1-2-24);

 8 - [(2-methoxybenzoyl) amino] -3- (pyridin-4-yl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-

25);

 8 - [(2-ethoxybenzoyl) amino] -3- (pyridin-3-yl) - [1, 2,4] triazolo [4,3-a] pyridine (G-2-

26);

 8 - [(2-chlorobenzoyl) amino] -3- (1-methylpiperidin-4-yl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-27);

 8 - [(2-chlorobenzoyl) amino] -3- (7-methylpiperidin-3-yl) - [1,2,4] triazolo [4, 3-aj pyridine (1-2-28);

 8 - [(2,6-dichlorobenzoyl) amino] -3- (T-methylpiperidin-3-yl) - [1,2,4] triazolo | 4,3-a] pyridine (1-2-29);

 8 - [(2,6-dimethylbenzoyl) amino] -3- (! -Methylpiperidin-3-yl) - [1, 2,4] triazolo | 4,3-a] pyridine (1-2-30);

 1- (3-cy lobutyl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (3,4-dimethoxyphenyl) urea (1-3-01);

 1- (3-cyclobutyl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (2-methoxy-5-methylpheiyl) - urea (1-3-02);

 1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (3,4-ethylenedio syphenyl) urea (1-3-03);

1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (2-phenylethyl) urea (1-3-04); 1- (3-cy lobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (3,4-methylenedioxyphenyl) urea (1-3-05);

 1- (3-qi lobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) urea 3-06);

 1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (tetrahydrofuryl-2-ethyl) urea (1-3-07);

 1- (3-cy lobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (2-methoxy arbonylthienyl-3) -urea (1-3-08);

 1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (3-acetylphenyl) urea 3-09);

 1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (4-methoxy-2-methylphenyl) - urea (1-3-10) ;

 1 - (3-cyclobutyl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (4-methoxy-3-fluorophenyl) urea (1-3-11);

 1- (3-cyclopentyl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) urea (1-3-12);

 1- (3-cyclohexyl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) urea (1-3-13);

 1- {3- (1M-methylpiperidin-4-yl) [1, 2,4] triazolo [4,3-a] pyridin-8-yl} -3- (furyl-2-methyl) -urea (1- 3-14);

 1- {3- (Y-methylpiperidin-3-yl) [1,2,4] triazolo | 4,3-a] pyridin-8-yl} -3- (furyl-2-methyl) -urea (1- 3-15);

 1- {3 - ^ - methylpiperidin-4-yl) [1,2,4] triazolo [4,3-a] pyridin-8-yl} -3- (2-methoxyphenyl) urea (1-3-16 );

 1- {3- (1M-methylpiperidin-4-yl) [1,2,4] triazolo [4,3-a] pyridin-8-yl} -3- (3,4-dimetho-siphenyl) -urea (1 -3-17);

 1- {3 - ^ - methylpiperidin-3-yl) [1,2,4] triazolo [4,3-a] pyridia-8-yl} -3- (2-methoxyphenyl) urea (1-3-18 );

1- {3- (TM-methylpiperidin-3-yl) [1,2,4] triazolo [4,3-a] pyridium-8-yl} -3- (3,4-dimethoxyphenyl) urea (1- 3-19); 1 - (3-pyrid-4-yl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) -urea (I-3-20 );

 1 - (3-pyrid-3-yl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) -urea (I- 3-21 );

 1 - (3-pyrid-4-yl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) -urea (I-3-22 );

 1 - (3-pyrid-3-yl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) -urea (I-3-23 );

 1 - {3- (T-methylpiperidin-4-yl) [1, 2,4] triazolo [4,3-a] pyridin-8-yl} -3-allylurea

(1-3-24);

 1 - {3- (1M-methylpiperidin-3-yl) [1, 2,4] triazolo [4,3-a] pyridin-8-yl} -3-allylurea

(1-3-25);

The subject of this invention is the pharmaceutically acceptable salts of the compounds of general formula I. A portion of the compounds of this invention contains ionic groups (secondary, tertiary amines) and can form salts which have been prepared by methods known in the art.

 The subject of this invention is a method for producing derivatives of [1, 2,4] triazolo [4,3-a] pyridines of general formulas 1-2 and 1-3 (Scheme 2):

 Scheme 2

Для этого из 2-хлор-З-нитропиридинов Ы получали соответствующие 2-гидразино-З- нитропиридины Ь2. Гидразины Ь2 цикло онденсировали с подходящим ацил-производным. получая [ 1 ,2,4]триазоло[4,3-а]пиридины ЬЗ. Далее нитропиридины ЬЗ восстанавливали водородом над палладием на угле и получали серию гетероциклических ам инов Ь4. Ацилирование ам инов Ь4 подходящими ацилгалогенидами (ацилхлоридом, ацилфторидом, ацилбромидом) в апротонном нейтральном растворителе (дихлорметан, диоксан, хлороформ и подобные) в присутствии основания (триэтиламин, DABCO, пиридин и подобные) при охлаждении приводило к серии веществ 1-2. Взаимодействие аминов Ь4 с изотиоцианатам и в нейтральном растворителе (этанол, дихлорметан, диоксан, хлороформ и подобные) приводило к серии веществ 1-3.

For this, the corresponding 2-hydrazino-3-nitropyridines L2 were obtained from 2-chloro-3-nitropyridines L. Hydrazines b2 were cyclone-condensed with a suitable acyl derivative. obtaining [1, 2,4] triazolo [4,3-a] pyridines b3. Next, nitropyridines L3 were reduced with hydrogen over palladium on charcoal and a series of heterocyclic amines L4 was obtained. Acylation of amines L4 with suitable acyl halides (acyl chloride, acyl fluoride, acyl bromide) in an aprotic neutral solvent (dichloromethane, dioxane, chloroform and the like) in the presence of a base (triethylamine, DABCO, pyridine and the like) upon cooling led to a series of substances 1-2. The interaction of L4 amines with isothiocyanates and in a neutral solvent (ethanol, dichloromethane, dioxane, chloroform and the like) led to a series of substances 1-3.

 The substituents R2, R3a and R3b, R4, R6 and B in Schemes 1 and 2 are defined above, X = O.

 The subject of this invention is an active component having the properties of an A2A receptor antagonist, which is a (substance) for the preparation of pharmaceutical compositions and finished dosage forms for the prevention and treatment of disorders of the CYS, neurodegenerative, inflammatory, infectious and oncological diseases and is a compound of the general formula I .

 The subject of this invention is new compounds of general formula I, which are an agent (adjuvant) for enhancing the immune response or action of drugs in the combined treatment of disorders of the central nervous system, neurodegenerative, inflammatory, infectious and oncological diseases.

 The subject of this invention is a pharmaceutical composition having antagonistic activity against an adenosine Α2Λ receptor, comprising, as an active component (substance) or agent (adjuvant), compounds of general formula I or their pharmaceutically acceptable salts in a therapeutically effective amount.

The subject of this invention is any of the aforementioned pharmaceutical compositions in the form of tablets, capsules and injections, ointments, gels and other formulations placed in a pharmaceutically acceptable package. Pharmaceutical compositions may include pharmaceutically acceptable excipients, namely, diluents, auxiliary agents, and / or carriers used in the pharmaceutical field. The pharmaceutical composition, along with the compound of general formula I or a pharmaceutically acceptable salt thereof, of the present invention, may include other active substances, provided that they do not cause undesirable effects.

 If it is necessary to use the pharmaceutical compositions of the present invention in clinical practice, they can be mixed for the manufacture of various forms, and they may include traditional pharmaceutical carriers; for example, oral forms (such as tablets, gelatine capsules, pills, solutions or suspensions); injection forms (such as injectable solutions or suspensions, or dry powder for injection, which requires the addition of water for injection before use); local forms (such as ointments or solutions).

 The carriers used in the pharmaceutical compositions of the present invention are carriers that are used in the pharmaceutical industry to obtain common forms, including: in oral forms, binders, lubricants, disintegrants, solvents, diluents, stabilizers, suspending agents, colorless are used agents, flavoring agents of taste; antiseptic agents, solubilizers, stabilizers are used in injection forms; in local forms, bases, diluents, lubricants, antiseptic agents are used.

 The subject of this invention is a method for preparing a pharmaceutical composition by mixing with an inert excipient, auxiliary agent, carrier and / or solvent of at least one active component (substance) of the general formula I or a pharmaceutically acceptable salt thereof in a therapeutically effective amount.

The subject of this invention is a method for selectively inhibiting the activity of an adenosine A2A receptor, which consists in the action of the active component (substance) of the general formula I on biological objects or samples whose functions are regulated by A2A adenosine receptors. The subject of this invention is a medicament having antagonistic activity with respect to the adenosine A2A receptor, in the form of tablets, capsules or injections, placed in a pharmaceutically acceptable package intended for the prophylaxis and treatment of disorders of CYS. neurodegenerative, inflammatory, infectious and oncological diseases in humans and warm-blooded animals, including a new active component (substance) of general formula I or a pharmaceutical composition in a therapeutically effective amount.

 Medicines can be administered orally or parenterally (for example, intravenously, subcutaneously, intraperitoneally or topically). The clinical dosage of an agent of the general formula I in patients can be adjusted depending on the therapeutic efficacy and bioavailability of the active ingredients in the body, their metabolic rate and excretion from the body, as well as on the patient’s age, gender and disease. In this case, the daily dose in adults is usually 10 ~ 500 mg, preferably 50 ~ 300 mg. In accordance with the instructions of a doctor or pharmacist, these drugs can be taken several times during certain periods of time (preferably from one to six times a day).

 The subject of the present invention is a method for the prophylaxis and treatment of disorders of CYS, neurodegenerative, inflammatory, infectious and oncological diseases in animals and humans, which consists in administering in an effective amount to a patient a drug or pharmaceutical composition comprising a new active component (substance) general formula I, in a therapeutically effective amount.

The best embodiment of the invention

The invention is illustrated, but not limited to the following examples and. Initial reagents and physicochemical methods of proofing the synthesis of synthesized substances and their purity.

 All solvents and reagents were obtained from commercial sources such as Acros (Belgium), Sigma-Aldrich (USA), Lancaster (England) and ChemDiv (USA). Solvents and reagents were used without further purification. 'H-NMR spectra were recorded on a Bruker DPX-400 spectrometer (400 MHz, 27 ° C). Chemical shifts are given on a scale of δ (ppm), the internal standard is tetramethylsilane.

LC-MS characteristics of the claimed compounds (Tables 5-7) were determined using a Shimadzu HPLC unit equipped with a Waters XBridge Ci ₈ 3.5 mm column (4.6 mm ^χ 150 mm), a PE SCIEX API 150 EX mass detector, or a Shimadzu detector spectrophotometric detector (λ , 220 and 254 nm). According to LC-MS data, all synthesized compounds had a basic substance content above 95%.

 Analytical TLC was performed on silica gel on Si lufol UV254 aluminum plates (5 cm x 15 cm) (avalier, Czech Republic) or on glass plates with a 0.25 mm layer of silica gel 60 F254 (Merck, Germany). Visualization was carried out using UV light at a wavelength of 254 nm. Silica gel 5-40 μτη (Chemapol, Czech Republic) and 63 μτη (EM Science, USA) were used for chromatographic purification.

Production Methods and NMR Characteristics of the Compounds of the Invention Example 1. Synthesis of ethyl 2-hydrazioyl-nicotinic acid / yuta a2-1

a2-1

a2-1

See Scheme l, a2, where R2 = H. A solution of ethyl 2-chloronicotinate al-1 (10 g, 53.9 mmol) and anhydrous hydrazine (4.08 g, 127.6 mmol) in 200 ml of dioxane was stirred at 60 ° C for 12 hours. The mixture was cooled, concentrated in vacuo and dissolved in 35 ml of absolute methanol, removing the precipitate. The methanol was evaporated, the product a2-1 crystallized under absolute ether. Yield: 5.4g

(55%). MB 181; LC MS m / z 1 82 (M + H).

 Example 2. General method for the synthesis of ethyl esters of 2 - [(2-aggl-substituted) hydrazinyl] -nicotinic acids.

 A suspension of carboxylic acid (45.8 mmol), hydroxybenzotriazole HOBt (6.25 g, 46 mmol) and TM-ethyl-3'-3-dimethylaminopropylcarbodiimide EDC (8.74 g, 46 mmol) in dry dichloromethane (200 ml) was stirred at room temperature for 10 minutes then a solution of hydrazine a2-1 (9.5 g, 52.4 mmol) in 1 50 ml of dichloromethane was added to the mixture. The reaction mixture was stirred at room temperature from 2.0 to 16 hours, the precipitate was removed, and then washed with water (3x 100 ml). The organic layer was dried over MgS04 and evaporated. The resulting solid residue was used further without further purification. Output: 50-

85%

 Example 3. General method for the synthesis of ethyl esters of 3-substituted

 a] pyridine-8-carboxylic acids az (see Scheme 1).

To a solution of 3.0 mmol of ethyl 2 - [(2-acyl-substituted) hydrazinyl] -nitrate acid in 150 ml of dichloromethane was added 1.5 ml of POC13, then the mixture was boiled for 2.5–20 hours, monitoring the progress of the reaction using TLC. The mixture was cooled and concentrated in vacuo. The residue was dissolved in 200 ml of ethyl acetate, the resulting mixture was treated with an aqueous solution of NaHC03 and dried over magnesium sulfate. After evaporation of ethyl acetate, heterocyclic esters of az were obtained in yields of 70-90%. Scheme 1

where R2, R ₃ a and R ₃ b, B have the above meanings, X = OH.

Example 4. The general method for the synthesis of 3-substituted [1,2,4] trszolo [4,3-a pyridine-8-carboxylic acids a4 (see Scheme 1).

 To a cooled (0 ° C) solution of 1.5 mmol of a3 ether in 10 ml of ethanol was added with stirring 1.5 ml of a 2.5 N aqueous solution of NaOH. The mixture was warmed to room temperature for 3 hours, the reaction was stopped by adding concentrated hydrochloric acid (to pH = 2-3). The mixture was evaporated, the residue was washed with water and dried. A4 acid yield: 70-95%.

Example 5. General method for the synthesis of amides of 3-substituted [1, 2, 4] tr azolo [4,3-a] pyridine-8-carboxylic acids 1-1 The synthesis was carried out in accordance with Scheme 1. A mixture of acid a4 (1 .0 mmol). amine (1 .1 mmol), carbodiimide EDC (1 .0 mmol) and 1-hydroxybenzotriazole (1 .0 mmol) in 10 ml of DMF was stirred for 2-20 hours at room temperature, monitoring the progress of the reaction using LS-MS. At the end of the reaction, the mixture was diluted with 30 ml of water and extracted with methylene chloride (3x30 ml). The organic layer was dried over magnesium sulfate and evaporated. The product was purified by chromatography on silica gel (eluent CH2C12 / MeOH 19: 1). The yields of amides 1-1 25-85%.

 Thus, compounds of the general formula 1-1-01 to 1-1-55, shown in Table 4, were prepared.

Table 4. Compounds of general formula 1-1, their LC MS analysis and activity data.

Below are the NMR spectral data of some of the obtained amides of the compounds of general formula 1-1:

 1-1-01. IH NMR (400 MHz, DMSO-d6) δ 3.83 (s, 3H), 6.74 (dt, J = 7.6, 2.1 Hz, IH), 7.25 - 7.36 (m, 3H), 7.47 (t, J = 8.8 Hz, 2H), 7.56 (t, J = 2.1 Hz, IH), 8.00 (dd, J = 8.8, 5.4 Hz, 2H), 8.27 (d, J = 7.0 Hz, 1 H), 8.76 (d, J = 6.9 Hz , 1 H), 11.71 (s, 1 H)

 T-l-02. IH NMR (400 MHz, DMSO-d6) δ 3.84 (s, 3H), 6.74 (dt, J = 7.1, 2.4 Hz, IH), 7.30 (m, 3H), 7.51 (m, 2Ы), 7.57 (m, IH), 7.75 (m, IH), 7.84 (td, J = 7.4, 2.0 Hz, IH), 8.31 (d, J = 7.0 Hz, 1 H), 8.48 (dd, J = 7.0, 3.1 Hz, 1 H ), 11.65 (s, 1 H)

 1-1-03. IH NMR (400 MHz, DMSO-d6) δ 3.88 (s, 3H), 7.25 (m, 2H), 7.33 (d, J = 8.5 Hz, 111), 7.60 (m, 2H), 7.70 (m, 3H) , 7.79 (d, J = 8.2 Hz, IH), 7.99 (d, J = 8.1 Hz, IH), 8.33 (d, J = 6.9 Hz, 1 H), 8.38 (d, J = 7.0 Hz, 1 H) , 8.50 (d, J = 7.5 Hz, 1 H), 8.58 (d, J = 8.5 Hz, 1 H), 12.27 (s, 1 H) 1-1-04.1 H NMR (400 MHz, DMSO-d6) δ 2.40 (s, 3H), 3.86 (s, 3H), 6.99 (d, J = 7.6 Hz, IH), 7.21 (m, 2H), 7.30 (m, 2H), 7.65 (m, 4H), 8.27 (m , 2Y), 11.68 (s, 1 H)

 1-1-05. IH NMR (400 MHz, DMSO-d6) δ 2.40 (s, 3H), 3.91 (s, 3H), 6.98 (d, J = 7.8 Hz, 1 H), 7.19 (d, J = 8.7 Hz, 2H), 7.24 (t, J = 7.0 Hz, 1 H), 7.28 (t, J = 7.8 Hz, 1 H), 7.63 (bs, 1 H), 7.66 (d, .1 = 8.0 Hz, 1 H), 7.86 ( d, J = 8.7 Hz, 2H), 8.25 (d, J = 7.0 Hz, 1 H), 8.72 (d, J = 7.0 Hz, 1 H), 11.71 (s, IH) 1-1-06.1 H NMR ( 400 MHz, DMSO-d6) δ 7.17 (t, J = 7.6 Hz, 1 H), 7.30 (t, J = 7.0 Hz, 1 H), 7.42 (t, J = 7.6 Hz, 2H), 7.52 (m, 2H), 7.75 (m, IH), 7.84 (m, 3H), 8.31 (d, J = 7.0 Hz, IH), 8.48 (dd, J = 6.9.3.1 Hz, IH), 11.67 (s, IH)

1-1-07. IH NMR (400 MHz, DMSO-d6) δ 1.34 (d, J = 6.5 Hz, 6H), 4.24 (m, III), 7.14 (t, J = 7.0 Hz, 1 H), 7.19 (t, J = 7.5 Hz, 1 H), 7.29 (d, J = 8.3 Hz, 1 H), 7.58 (d, J = 7.5 Hz, IH), 7.64 (t, J = 8.3 Hz, 1 H), 8.15 (m, 2H) , 9.51 (d, J = 7.6 Hz, 1 H) 1-1-08. IH NMR (400 MHz, DMSO-d6) δ 2.35 (s, 3Η), 7.22 (d, J = 8.1 Hz, 2H), 7.29 (t, J = 7.0 Hz, IH), 7.51 (m, 2H), 7.72 (m, 3H), 7.84 (td, J = 7.4, 1.7 Hz, IH), 8.30 (d, J = 7.0 Hz, IH), 8.46 (dd, J = 7.0, 3.1 Hz, 1 H), 11.59 (s , 1 H)

 1-1-09. IH NMR (400 MHz, DMSO-d6) δ 3.86 (s, 3H), 7.21 (m, 4H), 7.31 (d, J = 8.5 Hz, IH), 7.65 (m, 2H), 7.86 (m, 2H) , 8.27 (m, 2H), 11.72 (s, 1 H)

 1-1-10. IH NMR (400 MHz, DMS0-d6) δ 3.89 (s, 3H), 3.93 (s, 3H), 4.66 (d, J = 5.8 Hz, 2H), 6.91 (t, J = 7.4 Hz, IH), 7.00 (d, J = 8.1 Hz, IH), 7.17 (m, 3H), 7.27 (t, J = 7.4 Hz, IH), 7.31 (d, J = 7.4 Hz, IH), 7.81 (d, J = 8.6 Hz , 2H), 8.14 (d, J = 7.0 Hz, IH), 8.65 (d, J = 7.0 Hz, IH), 10.04 (l, J =

5.8 Hz, IH)

 1-1-11. IH NMR (400 MHz, DMS0-d6) δ 3.93 (s, 3H), 4.67 (d, J = 5.9 Hz, 2H), 6.91 (t, J = 7.3 Hz, IH), 7.01 (d, J = 8.1 Hz , IH), 7.25 (m, 2H), 7.32 (d, J = 7.4 Hz, IH), 7.49 (m, 211), 7.73 (m, IH), 7.80 (t, J = 7.4 Hz, IH), 8.20 (d, J = 6.9 Hz, IH), 8.39 (dd, J = 7.1, 3.2 Hz, IH), 9.99 (t, J =

5.9 Hz, IH)

 1-1-12.1 H NMR (400 MHz, DMS0-d6) δ 3.86 (s, 3H), 6.95 (m, 1 H), 7.21 (m, 211), 7.31 (d, J = 8.4 Hz, 1 H) , 7.46 (m, 2H), 7.65 (m, 2H), 7.89 (dt, J = 11.4, 2.2 Hz, 1 H), 8.28 (d, J = 7.0 Hz, 2H), 11.86 (s, IH)

 1-1-13.1 H NMR (400 MHz, DMS0-d6) δ 3.90 (s, 3H), 7.18 (m, 3H), 7.24 (t, J = 7.0 Hz, 1 H), 7.43 (t, J = 8.1 Hz, IH), 7.64 (d, J = 8.1 Hz, IH), 7.85 (d, J = 8.8 Hz, 2H), 8.06 (t, J = 2.1 Hz, IH), 8.25 (d, J = 7.0 Hz, 1 H), 8.73 (d, J = 7.0 Hz, 1 H), 11.85 (s, 1 H)

 1-1-14. IH NMR (400 MHz, DMS0-d6) δ 7.19 (dd, J = 7.9, 2.1 Hz, IH), 7.27 (t, J = 7.0 Hz, IH), 7.45 (m, 3H), 7.63 (d, J = 8.3 Hz, IH), 7.99 (dd, J - 8.7, 5.3 Hz, 2H), 8.06 (t, J = 2.1 Hz, 1 H), 8.27 (d, J = 7.0 Hz, 1 H), 8.77 (d, J = 7.0 Hz, 1 H), 11.81 (s, 1 H)

 1-1-15. IH NMR (400 MHz, DMS0-d6) δ 7.20 (dd, J = 8.0, 2.0 Hz, IH), 7.30 (t, J = 7.0 Hz, 111), 7.44 (t, J = 8.1 Hz, IH), 7.52 (m, 2H), 7.66 (d, J = 8.2 Hz, OH), 7.75 (m, IH), 7.84 (t, J = 7.4 Hz, 1 H), 8.08 (t, J = 2.0 Hz, 1 H) , 8.31 (d, J = 7.0 Hz, 1 H), 8.49 (dd, J = 7.0, 3.1 Hz, 1 H), 11.75 (s, IH) 1-1-16. IH NMR (400 MHz, DMS0-d6) δ 2.56 (s, 3H), 3.86 (s, 3H), 7.10 (t, J = 7.4 Hz, IH), 7.22 (m, 3H), 7.30 (m, 2H) , 7.65 (m, 2H), 8.27 (m, 2H), 8.31 (d, J = 7.0 Hz, 1 H), 11.54 (s, 1 II)

1-1-17. IH NMR (400 MHz, DMS0-d6) δ 2.56 (s, 3H), 3.91 (s, 3H), 7.09 (t, J = 7.4 Hz, 111), 7.19 (d, J = 8.7 Hz, 2H), 7.26 (m, 3H), 7.86 (d, J = 8.7 Hz, 2Ы), 8.29 (d, J = 7.5 Hz, 2Ы), 8.74 (d, J = 7.0 Hz, IH), 11.56 (s, IH) 1-1-19. IH NMR (400 MHz, DMSO-d6) δ 2.29 (s, 311), 3.87 (s, 3H), 6.76 (d, J = 7.5 Hz, 1 II), 6.80 (d, J = 7.7 Hz, IH), 7.04 (t, J = 7.8 Hz, IH), 7.21 (m, 2H), 7.31 (d, J = 8.4 Hz, IH), 7.65 (m, 211), 8.26 (m, 2H), 9.37 (s, 1 H), 10.99 (s, IH)

 1-1-20.1 H NMR (400 MHz, DMSO-d6) δ 1.00 - 1.35 (m, 5H), 1.57- 1.89 (m, 6H), 3.37 (t, J = 6.3 Hz, 2H), 7.23 (t, J = 7.0 Hz, 1 H), 7.49 (m, 2 H), 7.72 (m, 1 H), 7.80 (t, J = 7.4 Hz, 1 H), 8.18 (d, J = 7.0 Hz, 1 H), 8.39 (dd, J = 7.0, 3.3 Hz, 1 H), 9.59 (t, J = 5.9 Hz, 1 H)

 1-1-21. IH NMR (400 MHz, DMSO-d6) δ 2.37 (s, 3H), 2.43 (s, 3H), 7.03 (d, J = 7.4 Hz, 1 W), 7.14 (t, J = 7.8 Hz, IH), 7.30 (t, J = 7.0 Hz, IH), 7.51 (m, 2H), 7.75 (m, III), 7.85 (t, J = 7.3 Hz, IH),

7.95 (d, J = 8.5 Hz, 1 H), 8.34 (d, J = 7.0 Hz, 1 H), 8.48 (dd, J = 7.0, 3.3 Hz, 1 H), 11.42 (s, 1 I I)

1-1-23. IH NMR (400 MHz, DMSO-d6) δ 2.26 (s, 3H), 2.30 (s, 3H), 7.15 (d, J - 8.0 Hz, 111), ^' 7.29 (t, J = 7.0 Hz, IH), 7.51 (m, 2H), 7.58 (m, 2H), 7.75 (m, IH), 7.84 (t, J = 7.4 Hz, IH), 8.29 (d, J = 7.0 Hz, 1 H), 8.46 (dd, J = 7.0, 3.2 Hz, 1 H), 11.54 (s, 1 H)

 1-1-24. IH NMR (400 MHz, DMSO-d6) δ 2.36 (s, 6H), 3.86 (s, 3H), 6.81 (s, IH), 7.21 (m, 2H),

7.31 (d, J = 8.4 Hz, 1 H), 7.46 (s, 211), 7.65 (m, 2H), 8.26 (m, 2H), 11.63 (s, 1 H)

 1-1-25. IH NMR (400 MHz, DMSO-d6) δ 1.34 (t, J = 7.5 Hz, 311), 2.94 (q, J = 7.5 Hz, 2H), 7.14 (t,

J = 7.5 Hz, 1 H), 7.29 (m, 3H), 7.52 (m, 2H), 7.75 (m, 1 H), 7.86 (t, J = 7.4 Hz, 1 H), 8.23 (d, J = 8.1

Hz, 1 H), 8.35 (d, J = 7.0 Hz, 1 H), 8.49 (dd, J = 6.9, 3.2 Hz, 1 H), 11.53 (s, 1 H)

 1-1-36. IH NMR (400 MHz, DMSO-d6) δ 4.71 (d, J = 5.5 Hz, 2H), 6.38 (m, 2H), 7.20 (t, J = 6.9

Hz, IH), 7.44 (t, J = 8.5 Hz, 2H), 7.55 (s, IH), 7.95 (dd, J = 8.5, 5.3 Hz, 2H), 8.18 (d, J = 6.9 Hz,

IH), 8.69 (d, J = 6.9 Hz, IH), 9.91 (t, J = 5.5 Hz, 111)

 1-1-37. IH NMR (400 MHz, DMSO-d6) δ 4.72 (d, J = 5.8 Hz, 2H), 6.39 (m, 2H), 7.23 (t, J = 7.0 Hz, 1 H), 7.49 (m, 2H), 7.55 (d, J = 1.8 Hz, 1 H), 7.73 (m, 1 H), 7.79 (t, J = 7.4 Hz, 1 H), 8.22 (d, J = 7.0 Hz, IH), 8.41 (dd, J = 7.0, 3.2 Hz, 1 H), 9.88 (t, J = 5.8 Hz, 1 H)

 1-1-38. IH NMR (400 MHz, DMSO-d6) δ 1.57 (m, 4H), 1.68 (m, 4H), 1.85 (m, 2H), 3.28 (m, 2H), 3.65 (t, J = 6.2 Hz, 2Ы) , 7.07 (t, J = 6.8 Hz, IH), 7.33 (d, J = 6.7 Hz, IH), 7.43 (t, J = 8.8 Hz, 2H),

7.96 (dd, J = 8.8, 5.3 Hz, 2H), 8.55 (d, J = 7.1 Hz, 1 H)

1-1-39. IH NMR (400 MHz, DMSO-d6) δ 0.74 (d, J = 6.5 Hz, 3H), 0.86 (m, IH), 0.99 (d, J - 6.5 Hz, 3H), 1.42 -2.09 (m, 3H) , 2.31 (m, IH), 2.55 - 2.91 (m, IH), 3.24 -3.69 (m, 111), 4.59 (m, IH), 7.06 (t, J = 6.9 Hz, IH), 7.36 (d, J = 6.8 Hz, IH), 7.43 (t, J = 8.8 Hz, 2H), 7.97 (m, 2H), 8.56 (d, J = 7.1 Hz, IH) 1-1-40. 1H NMR (400 MHz. DMSO-d6) δ 1.74 (d, J = 13.7 Hz, 2H), 2.32 (m, 2H), 3.30 (m, 4H), 3.89 (s, 3H), 5.43 (s, 1H) , 7.04 (t, J = 6.9 Hz, 1H), 7.15 (d, J = 8.4 Hz, 2H), 7.33 (d, J = 8.6 Hz, 2H), 7.51 (d, J = 8.6 Hz, 2H), 7.79 (d, J = 8.4 Hz, 2H), 7.91 (m, 1 H), 8.48 (d, J = 6.9 Hz, 1 H), 9.43 (s, 1H)

 1-1-41. 1H NMR (400 MHz, DMSO-d6) δ 1.31 (m, 2H), 1.52 (m, 1H), 1.77 (d, J = 14.3 Hz, 1H), 1.84 (m, 1H), 2.58 (d, J = 7.1 Hz, 2H), 2.81 (t, J = 12.5 Hz, 1H), 3.03 (t, J = 12.6 Hz, 1H), 3.42 (d, J = 13.1 Hz, 1H), 4.60 (d, J = 12.9 Hz , 1H), 7.06 (t, J = 6.9 Hz, 1H), 7.16 (m, 3H), 7.25 (m, 211), 7.36 (d, J = 6.7 Hz, 1 H), 7.42 (t, J = 8.7 Hz, 2H), 7.95 (dd, J = 8.7, 5.5 Hz, 2H), 8.54 (d, J = 7.1 Hz, 1H)

 1-1-42.1H NMR (400 MHz, DMSO-d6) δ 2.05 (m, 2H), 2.90 (t, J = 6.7 Hz, 2H), 3.78 (s, 2H), 7.02 (m, 4H), 7.17 (d, J = 8.0 Hz, 1H), 7.41 (t, J = 8.8 Hz, 2H), 7.45 (m, 1H), 7.94 (dd, J = 8.8, 5.4 Hz, 2H), 8.55 (d, J = 7.0 Hz, 1H)

 1-1-43. 1H NMR (400 MHz, DMSO-d6) δ 1.50 (d, J = 13.0 Hz, 1H), 1.78 (d, J = 13.8 Hz, 1H), 2.04 (m, 2H), 3.30 (m, 2H), 3.53 (t, J = 13.0 Hz, 1H), 4.58 (d, J = 12.7 Hz, 1H), 5.22 (s, 1H), 7.08 (t, J = 6.9 Hz, 1H), 7.35 (d, J = 8.6 Hz , 2H), 7.43 (m, 3H), 7.53 (d, J = 8.6 Hz, 2H), 7.96 (dd, J = 8.8, 5.3 Hz, 2H), 8.55 (d, J = 7.1 Hz, 1H)

 1-1-44.1H NMR (400 MHz, DMSO-d6) δ 2.26 (s, 3H), 7.01 (t, J = 7.0 Hz, 1H), 7.15 (dd, J = 8.6, 2.4 Hz, 1H), 7.21 (d, J = 2.4 Hz, 1H), 7.60 (m, 3H), 7.84 (d, J = 7.1 Hz, 2H), 7.89 (d, J = 6.7 Hz, 1 H), 7.97 (d, J = 8.6 Hz, 1 H), 8.48 (d, J = 6.9 Hz, 1 H), 9.93 (s, IH)

 Example 6. Synthesis of 3-nitropyridyl-2-hydrazine L2-1 (Scheme 2, L2, R2 = H).

(see Scheme 2)

 s

A solution of 0.6 mol of chloropyrididium in 2 liters of ethanol was placed in a conical flask and 2.5 mol of hydrazine hydrate was added in portions. The mixture was stirred at room temperature for two hours. The precipitate was filtered off, washed with water and cold ethanol, and dried in air. Yield b2-1: 95%.

B2-1

 Example 7. General method for the synthesis of 3-substituted 8-nitro [1, 2, 4] triazolo / 4,3-a] pyridines L3 (see Scheme 2)

 In a suspension of 5 mmol of hydrazine L2-1 in 50 ml of ethanol, 5.5 mmol of the corresponding orthoester was added and boiled with stirring for 1-2 hours. The mixture was cooled, the precipitate was filtered off, washed with ether and dried. Product yield b3: 50-

80%

 Example 8. General method for the synthesis of 3-substituted 8-amino [1,2, 4 / triazolo / 4, 3-a / pyridine b4 (Scheme 2).

 In 250 ml. an autoclave was placed 0.05 mol of compound L3 in 100 ml of methanol, I g of 10% Pd / C and hydrogenated at room temperature until the calculated amount of hydrogen was completely absorbed. The mixture was filtered, the organics were evaporated, the precipitate was washed with acetonitrile, dried. Yield b4: 50-70%.

Пример 9. Общий метод синтеза З-замещенных 8-ациламино[Ч.2, 4/^' триазоло 4.3- aJnupuduHoe 1-2

Example 9. General method for the synthesis of 3-substituted 8-acylamino [Part 2, 4 / ^' triazolo 4.3-aJnupuduHoe 1-2

 The synthesis was carried out in accordance with Scheme 2. Amine L4 (0.001 mol) was dissolved in 3 ml of dichloromethane, triethylamine (0.002 mol, 0.202 g) was added and cooled to 0 ° C. With vigorous stirring, 0.0012 mol of R4C (0) X chloride was carefully added and the mixture was warmed to room temperature. After three hours, the reaction mixture was diluted with dichloromethane (30 ml), washed with 2.0 N hydrochloric acid (2 * 1 5 ml), dried over sodium sulfate, and chromatographed with CH2C12 / EHN (column height 5 cm, width 1 cm). Received pure products 1-2 with yields of 60-90%.

 Thus, compounds 1-2-01 to 1-2-30, which are shown in Table 5, were prepared.

Таблица 5.

Table 5.

MB 363.5;

 1-2-30 LC MS m / z A

 364 (M + l)

Below are the NMR spectral data of some of the obtained amides 1-2: 1-2-04. 1H NMR (400 MHz, DMSO-d6) δ 1.75 (t, J = 7.0 Hz, 3H), 2.06 (m, 1H), 2.19 (m, 1H), 2.54 (m, 4H), 4.02 (p, J = 8.5 Hz, 1 H), 4.42 (q, J = 7.0 Hz, 2H), 6.90 (t, J = 7.1 Hz, 1 H), 7.13 (t, J = 7.4 Hz, 1H), 7.27 (d, J = 8.4 Hz, 1H), 7.58 (td, J = 7.2, 1.9 Hz, 1H), 7.94 (d, J = 7.1 Hz, 1H), 8.13 (dd, J = 7.9, 1.9 Hz, 1 H), 8.25 (d , J = 7.1 Hz, 1 H), 11.09 (s, 1 H)

 1-2-07. 1H NMR (400 MHz, DMSO-d6) δ 2.05 (m, 1H), 2.21 (m, 1H), 2.55 (m, 4H), 4.05 (d, J = 8.0 Hz, 1H), 6.94 (t, J = 7.1 Hz, 1H), 7.06 (t, J = 8.0 Hz, 1H), 7.23 (t, J = 8.0 Hz, 1H), 7.48 (m, 2H), 7.67 (d, J = 8.1 Hz, 1 H), 8.02 (m, 2H), 9.99 (s, 1 H), 11.92 (s, 1 H)

 1-2-10.1H NMR (400 MHz, DMSO-d6) δ 2.04 (m, 1H), 2.19 (m, 1H), 2.52 (m, 4H), 4.04 (p, J = 8.4 Hz, 1H), 6.93 (t, J = 7.1 Hz, 1H), 7.18 (m, 1H), 7.83 (d, J = 7.1 Hz, IH), 8.04 (d, J = 7.1 Hz, 1H), 8.11 (d, J = 4.1 Hz , IH), 10.43 (s, 1H)

Example 10. General method for the synthesis of 3-substituted 8-ureido [1, 2,4] triazolo _\ 14,3-a] pyridines 1-3

 The synthesis was carried out in accordance with Scheme 2. Amine L4 (0.001 mol) was dissolved in 3 ml of dichloromethane, triethylamine (0.002 mol, 0.202 g) was added and cooled to 0 ° C. With vigorous stirring, 0.0012 mol of R6NCO isothiocyanate was added and the mixture was warmed to room temperature. After 1-3 hours, the reaction mass was diluted with dichloromethane (30 ml), washed with 2.0 N hydrochloric acid (2x15 ml), dried over sodium sulfate and chromatographed with CH2C12 / EHN (column height 5 cm, width 1 cm). Received pure products 1-3 with yields of 60-90%.

Thus, compounds 1-3-01 -1-3-25, shown in Table 6, were obtained. Table 6. The compounds of General formula 1-3, the data of their LC MS analysis and activity.

Below are the NMR spectral data of some of the obtained urea 1-3: 1-3.03.1 H NMR (400 MHz, DMSO-d6) δ 2.04 (m, 1H), 2.18 (m, 1H), 2.53 (m, 4H), 4.00 (p, J =

8.3 Hz, 1H), 4.20 (m, 4H), 6.74 (m, 2H), 6.84 (t, J = 7.1 Hz, 1H), 7.10 (d, J = 2.4 Hz, 1H), 7.79 (d, J = 6.8 Hz, 1 H), 7.88 (d, J = 7.3 Hz, 1 H), 9.13 (s, 1 H), 9.26 (s, 1 H)

 1-3-06. 1H NMR (400 MHz, DMSO-d6) δ 2.03 (m, 1H), 2.17 (m, 1H), 2.50 (m, 411), 3.98 (p, J =

8.4 Hz, 1H), 4.33 (d, J = 5.5 Hz, 2H), 6.25 (d, J = 3.1 Hz, 1H), 6.36 (dd, J = 3.1, 1.8 Hz, 1H), 6.80 (t, J = 7.1 Hz, 1H), 7.46 (t, J = 5.5 Hz, 1H), 7.51 (d, J = 1.8 Hz, 1H), 7.75 (d, J = 6.9 Hz, 1H), 7.84 (d, J = 7.2 Hz , 1H), 9.07 (s, 1H)

 1-3-08.1H NMR (400 MHz, DMSO-d6) δ 2.05 (m, 1H), 2.18 (m, 1H), 2.54 (m, 4H), 3.86 (s, 311), 4.01 (p, J = 8.2 Hz, 1H), 6.85 (t, J = 7.1 Hz, 1H), 7.73 (d, J = 5.5 Hz, 1 H), 7.84 (d, J = 6.9 Hz, 1H), 7.92 (d, J = 7.5 Hz, 1H), 7.97 (d, J = 5.5 Hz, 1H), 10.11 (s, 1H), 10.74 (s, 1H)

1-3-10.1 H NMR (400 MHz, DMSO-d6) δ 2.04 (m, 1 H), 2.19 (m, 1 H), 2.24 (s, 3H), 2.51 (m, 4H), 3.74 (s, 3H), 4.00 (p, J = 8.4 Hz, 1H), 6.70 (m, 2H), 6.82 (t, J = 7.1 Hz, 1H), 7.59 (d, J = 8.7 Hz, 1 H), 7.78 (d , J = 6.8 Hz, 1 H), 7.89 (d, J = 7.4 Hz, 1 H), 8.61 (s, 1 H), 9.52 (s, 1 H)

The antagonistic activity of the new compounds of general formula I and their pharmaceutically acceptable salts with respect to the adenosine A2A receptor was carried out ex vitro in a functional test on cells. In the experiment used cells ValiScreen cell line (PerkinElmer, USA) expressing the recombinant human adenosine A2A receptor.

 Tables 4-6 present data on the activity of some of the compounds of general formula I, confirming their high antagonistic activity with respect to the adenosine A2A receptor: A means the inhibition of A2A receptors by the compound at a concentration of 10 μΜ by more than 75%, B by more than 50% , C - more than 25%, D - more than 10%.

Example 11 General Method for the Synthesis of Salts of Compounds of General Formula I.

 Part of the compounds of this invention contains ionic groups (secondary, tertiary amines) and can form salts that have been obtained by methods and known in the art.

For this, for example, to a solution of a base in an inert solvent (alcohol, acetone, chloroform, ether, ethyl acetate), a solution of an equivalent amount (sometimes excess) of an organic or inorganic acid in an inert solvent was added and precipitation of the desired salt was achieved. The inorganic acid may be hydrochloric acid, phosphoric acid, sulfuric acid, nitric acid, hydrobromic acid or hydroiodic acid. The organic acid may be methanesulfonic acid, p-toluenesulfonic acid, acetic acid, trifluoroacetic acid, maleic acid, succinic acid, oxalic acid, benzoic acid, tartaric acid, fumaric acid, mandelic acid, propionic acid, citric acid, lactic acid, lactic acid , gluconic acid, galacturonic acid, glutamic acid, glutaric acid, glucuronic acid, aspartic acid, ascorbic acid, carboxylic acid or vanillic acid, but not limited to them. Table 7 presents examples of the obtained pharmaceutically acceptable salts and some of their properties. Table 7. Pharmaceutically acceptable salts of the compounds of general formula I

Biological tests and the activity of synthesized compounds.

Example 11. The study of the antagonistic activity of compounds of General formula J and their pharmaceutically acceptable salts with respect to the adenosine A2A receptor.

The antagonistic activity of the new compounds of general formula I and their pharmaceutically acceptable salts with respect to the adenosine A2A receptor was carried out ex vitro in a functional test on cells. In the experiment, cells of the ValiScreen cell line line (PerkinElmer, USA) expressing the recombinant human A2A type adenosine receptor were used. When receptors are stimulated in these cells by a CGS-21680 agonist (Tocris), adenylate cyclase is activated, which leads to an increase in the synthesis of intracellular cyclic adenosine monophosphate (cAMP or cAMP). The amount of cAMP was determined using LANCE technology (LANCE Ultra cAMP kit, PerkinElmer). By the ability of the test compounds to reduce the amount of cAMP synthesized in the presence of CGS-21680, their antagonistic activity was evaluated. AT W-6002 antagonist (Axon Medchem, Netherlands) described in the literature was used as a standard (comparison compound).

Cells were cultured in DMEM (PanEco, Russia) supplemented with 10% FBS (Biological Industries), a mixture of penicillin / streptomycin (PanEco) and G41 8 (Sigma) at a temperature of 37 ° С in an atmosphere of 5% С0 ₂ . Before the experiment, the cells were removed from the culture vial with Versen's solution (PanEco) and suspended in SB2 buffer (Hanks medium + 5 mM HEPES (pH 7.4) +0.1% BSA + 200 u Ro-20- 1 734 + 2U / mL ADA (adenosine deaminase)) to a density of 0.2 million cells per milliliter. ULight ^{1 M} -anti-cAMP Antibody (PerkinElmer) was added to the cell suspension 1: 150 (v ^/ v) and the mixture was poured into white 384-well plates (PerkinElmer) 5 μl (1000 cells) per well.

 Test compounds were dissolved in DMSO to a concentration of 6.32 mM and 3.16-fold serial dilutions in DMSO were prepared. The prepared serial dilutions were diluted 50 times with SB 1 buffer solution (Hanks' medium + 5 mM HEPES (pH 7.4) +0.1% BSA). The resulting solutions of the compounds in SB 1 buffer were mixed in a 1: 1 ratio with a solution of CGS-21680 (12.64 nM), previously prepared in SB3 buffer (SB 1 + 0. 1% Pluronic F 127). The resulting mixtures of test compounds with an agonist were added (5 μl in duplicates) to the plate wells containing 5 μl of cells (as described above) and the plates were incubated for 30 minutes at room temperature. Each plate also contained 16 holes for each control (MAX and MIN). MAX - cells with 3. 1 6 nM CGS 21680 (agonist concentration corresponding to ECod, that is, a concentration that causes 90% cell activity); the signal from these wells was used in the calculations as 100% activity (0% inhibition). MIN - cells with a mixture of 3. 16 nM CGS-21680 and 2 μM KW-6002 (the concentration of the antagonist corresponding to 1Cuo, that is, the concentration that causes 100% suppression of cell activity); the signal from these wells was used in the calculations as 0% activity (100% inhibition). In addition, each plate contained wells (in 4 repetitions), where the cells were treated with an agonist (CGS-21680) at different concentrations. The final concentration of DMSO in all wells was 1%.

The cAMP formed in the cells was quantified using the LAIMCE Ultra cAMP kit (PerkinElmer, USA), in accordance with the methodology recommended manufacturer. The fluorescent signal was measured on a VictorSV instrument (PerkinElmer) equipped with a built-in LANCE High Count program.

 The apparent affinity of the test compounds was determined by the formula:

K = IC ₅₀ l (\ + LIK _o ),

 where ICso is the antagonist concentration at which adenylate cyclase activity is 50% of the maximum, L is the concentration of CGS-21680 at which measurements are carried out (3.16 pM), and Ko is the apparent affinity constant of CGS-2 1,680, quantitatively corresponding to ECso ( concentration of half-maximal cell stimulation) for CGS-21680 and determined from the stimulation curves of cAMP accumulation in cells at different agonist concentrations.

 Tables 5-7 provide activity data for the compounds of general formula I.

Example 12. Radioligid analysis of the interaction of compounds of General formula I with adenosine A 1, A2A, A2B and A3 receptors.

A radioligand analysis of the interaction of compounds of general formula I with adenosine A1, A2A, A2B and A3 receptors was performed to determine the selectivity of the interaction of compounds of general formula I with adenosine A2A receptor. When determining the interaction of the studied compounds with the adenosine A2A receptor, membrane preparations were used, obtained from human kidney embryonic cells expressing the recombinant human A2A receptor. Receptor expression was 7 pmol / mg protein. As the radioligand used | ^J H] CGS 21680 at a concentration of 0.05 μM. Solutions of the test compounds were prepared in the same way as described in the functional test procedure, with the difference that, in addition to SB 1 medium, a buffer of the following composition was used: 50 mM Tris-HCl, pH 7.4, 10 tM MgCb, 1 t M EDTA, 2 U / mL Adenosine Deaminase. Membrane preparations were incubated in the presence of a mixture of the test compounds and [H] CGS 2 1680 for 90 min at 25 ° C, and the mixtures were filtered on GF glass fiber filters (Millipor, USA). The radioactivity on the filters was determined using a MicroBeta liquid-oscillation counter (PerkinElmer, USA). Nonspecific binding was measured in the presence of 50 μM NECA, which amounted to no more than 15% of the total binding. The affinity of the tested compounds was determined by the formula:

i = IC ₅₀ (l + L _D ),

where 1C ₅₀ is the concentration of the antagonist at which the binding of [ ³ H] CGS-21680 is reduced to 50% of the maximum, L is the concentration of [ ³ H] CGS-21 680, at which measurements are carried out (50 pM) and _D is the affinity constant [ ³ H] CGS-2 1680, quantitatively corresponding to the EC ₅₀ value (half-maximum binding concentration) for [H] CGS-21680, and determined from the radioactive binding curves at different concentrations of [H] CGS-21680 (K _D = 64 nM).

 Similarly investigated the interaction of new compounds of General formula I with adenosine A l, A2B and A3 receptors.

The radioligand analysis of the interaction of some compounds of the general formula I with adenosine A l, A2A, A2B and A3 receptors showed their high selectivity with respect to the adenosine A _2A receptor (Table 8).

Table 8. The activity and selectivity of compounds 1-2-01 and the reference ligand W-6002 under conditions of radioligand analysis in relation to adenosine A l, A2A, A2B and A3 receptors.

Example 13. Obtaining a pharmaceutical composition.

The pharmaceutical composition according to the invention is prepared using methods generally accepted in the art and includes a pharmacologically effective amount of a drug substance representing a compound of the formula I or a pharmaceutically acceptable salt thereof, usually comprising from 5 to 30% by weight, in combination with one or more pharmaceutically acceptable auxiliary additives, such as diluents, binders, disintegrating agents, adsorbents, flavoring agents, flavoring agents. In accordance with known methods, pharmaceutical compositions may be in various liquid or solid forms.

 Examples of solid dosage forms include, for example, tablets, pills, gelatine capsules, etc.

 Examples of liquid dosage forms for injection and parenteral administration include solutions, emulsions, suspensions, etc.

 Compositions, as a rule, are obtained using standard procedures involving the mixing of the active compound with a liquid or finely divided solid carrier.

 Example 100 mg of a composition containing 15.0 mg of the compound 3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methylphenylamide (compound 1-1-16)

 Compound 1-1-16 15.0 mg

 Lactose 40.0 mg

 Alginic acid 20.0 mg

 Citric Acid 5.0 mg

 Tragacanth 20.0 mg

 According to the invention, pharmaceutical compositions containing other compounds of the general formula I as a drug substance are likewise prepared.

Industrial applicability

 The invention can be used in medicine, veterinary medicine, biochemistry.

Claims

CLAIM 1. Substituted [1, 2,4] triazolo [4,3-a] pyridines of the general formula I, as well as their pharmaceutically acceptable salts

where A represents an optionally substituted aminocarbonyl group - NC (O) -, in which the amino group can be substituted and substituents can be selected from hydrogen, CrCalkyl, optionally substituted, C | -C ₃ alkoxy, C3-C ₆ cycloalkyl, 5- A 6-membered heteroaryl in which the heteroatoms are selected from oxygen or nitrogen;  aryl selected from phenyl, optionally substituted with hydroxy, C pCzalkyl, C 1 -C5 alkoxy, halogen, C | -C5 acylamino group, or naphthyl; or an amino group is selected from a C ₃ -C ₇ heterocyclyl containing 1 -2 heteroatoms in a ring selected from nitrogen, oxygen or sulfur, optionally substituted with hydroxy, C | - C5 & acyl, benzyl, phenyl, which may be substituted by halogen, wherein said heterocyclyl may be fused to a benzene ring;  an acylamino group in which the acyl is selected from C | -C ₆ alkylcarbonyl, wherein the alkyl may be substituted with phenyl substituted with phenyl, wherein the substituents are selected from C | -Salkalkoxy; A 5-membered heteroaryl with a heteroatom selected from an oxygen or sulfur atom; benzoyl, possibly substituted by CpSalkyl, CgC _b a coxy, C | -Salkylthio or halogen, methylenedioxy; heterocyclylcarbonyl in which heterocyclyl is selected from a 5-6 membered heterocyclyl, with 1 -2 heteroatoms selected from nitrogen, oxygen or sulfur, possibly fused to a benzene ring and optionally substituted With hC ^ alkyl, halogen;  or a ureido group in which one of the substituents on the terminal amido group is hydrogen, and the second substituent is selected from:  CpSalkyl substituted with phenyl, a 5-membered saturated or aromatic heterocyclyl, in which the heteroatoms are selected from oxygen or sulfur; C ₂ -C ₆ alkenyl; aryl selected from phenyl substituted with C ^ Czalkyl, C ₁ -C ₅ alkoxy, ethylenedioxy, methylenedioxy, halogen, C | -C ₃ alkylcarbonyl;  A 5 membered heterocyclyl in which the heteroatoms are selected from a sulfur or oxygen atom, and optionally substituted with an alkyloxycarbonyl group; B is a non-aromatic cyclic substituent selected from C ₄ - C ₆ cycloalkyl;  an aromatic cyclic substituent selected from phenyl which may be substituted with halogen, Ci-Szalkoxy; a non-aromatic 5-6 membered heterocyclic substituent with a nitrogen atom as a heteroatom, and optionally Ν-substituted with C | -C ₃ alkyl; aromatic 5-6 membered heterocyclic substituent in which heteroatoms are selected from nitrogen, oxygen or sulfur, and which may be substituted With | -C ₆ alkyl;  or an aromatic 5-6 membered heterocyclic substituent in which the heteroatom is selected from nitrogen, fused to a benzene ring; Rla, Rib and Rlc, independently represent H, C | -C ₃ alkoxy,  excluding connections:

2. Substituted [1, 2,4] triazolo [4,3-a] pyridines according to claim 1 of the general formulas 1-1, 1-2 or 1-3, or their pharmaceutically acceptable salts,

Where:  B has the meanings defined in claim 1; R2a, R2b and R2c independently represent H, C | -C ₃ alkoxy; R3a and R3b independently represent hydrogen, Ci-C ₅ alkyl optionally substituted with C i-Szalkoxy, C ₃ -C ₆ cycloalkyl, 5-6 membered heteroaryl in which the heteroatoms are selected from oxygen or nitrogen; aryl selected from phenyl, optionally substituted with hydroxy, Czalkyl, C 1 -C5 alkoxy, halogen, CpCazacylamino, or naphthalene; R3a and R3b may together form cyclic substituents, with the group R3a-N-R3b being a C ₃ -C ₇ heterocyclyl containing 1 -2 heteroatoms in the ring selected from nitrogen, oxygen or sulfur, optionally substituted with hydroxy, C | -C ₅ al silt benzyl, phenyl, which may be substituted by halogen, wherein said heterocyclyl may be fused to a benzene ring; R4 is Czalkyl, where alkyl may be substituted with phenyl, substituted by phenyl, in which the substituents are selected from C ^ Szalkoxy; A 5-membered heteroaryl with a heteroatom selected from an oxygen or sulfur atom; aryl selected from phenyl optionally substituted with Ci-Calkyl, Ci-Szalkalkoxy, C pCzalkylthio or halogen, methylenedioxy; heterocyclyl, in which heterocyclyl is selected from a 5-6 membered heterocyclyl, with 1 to 2 heteroatoms selected from nitrogen, oxygen or sulfur, possibly fused to a benzene ring and optionally substituted by CpC ₆ alkyl, halogen;  R5 is hydrogen; R6a and R6b independently represent hydrogen, C | -C ₃ alkyl substituted with phenyl, a 5-membered saturated or aromatic heterocyclyl in which the hetero atoms are selected from oxygen or sulfur; _C2-C6 alkenyl, aryl selected from phenyl, substituted C 1 to _C-5 alkyl, Ci-Szal oxy, ethylenedioxy, methylenedioxy, halogen, C | - With ₃ alkylcarbonyl;  R6a and R6b may together form cyclic substituents, wherein the group R6a-N-R6b is a 5-membered heterocycle in which heteroatoms are selected from a sulfur or oxygen atom, and optionally substituted with an alkyloxycarbonyl group; 3. Substituted [1, 2,4] triazolo [4,3-a] pyridines according to claim 1, which are: 3- (4-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-methoxyphenylamide (1-1-01);  3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-methoxyphenylamide (1-1-02);  3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid naphthyl-1-amide (1-1-03); 3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-methylphenylamide (1-1-04); 3- (4-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-ethylphenylamide (1-1-05);  3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid phenylamide (1-1 -06); 3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-propylamide (I-1-07);  3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 4-methylphenylamide (1-1-08);  3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 4-fluorophenylamide (1-1-09);  3- (4-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid (2-methoxyphenyl) methylamide (1-1-10);  3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid (2-methoxyphenyl) methylamide (1-1-11);  3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-fluorophenylamide (1-1-12);  3- (4-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-chlorophenylamide (1-1-13);  3- (4-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-chlorophenyl id (1 1-14);  3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridium-8-carboxylic acid 3-chlorophenyl id (1-1-15);  3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methylphenylamide (1-1-16);  3- (4-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methylphenylamide (1-1-17);  3- (2-methoxyphenyl) - | 1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-hydroxy-6-methylphenylamide (1-1-19);  3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid (cyclohexyl) methylamide (1-1-20); 3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridium-8-carboxylic acid 2,3- dimethylphenylamide (1-1-21);  3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3,4-dimethylphenylamide (1-1-23);  3- (2-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3,5-diethylphenylamide (1-1-24);  3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-ethylphenylamide id (1-1-25);  3- (pyrid-4-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 3-methylphenylamide (1-1-26);  3- (pyrid-4-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-methylphenylamide (I- 1-27);  3- (pyrid-3-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-methylphenylamide (1-1-28);  3- (pyrid-3-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-methoxyphenyl id (M-29);  3- (5-methylfuryl-2) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methoxyphenylamide (1-1-30);  3- (thienyl-2) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methoxyphenylamide (L-31); 3- (indol-2-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-methoxyphenylamide (1-1-32);  3- (Y-methylpiperidin-4-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-ethylphenyl id (1-1-33);  3-CM-methylpiperidin-4-yl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid 2-methoxyphenylamide (1-1-34);  3-cyclobutyl- [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methoxyphenylamide (L-35); 3- (4-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid (furan-2-yl) methylamide (1-1-36); 3- (2-fluorophenyl) - [1, 2,4] triazolo [4,3-a] pyridin-8-carboxylic acid (furan-2-yl) methylamide (1-1-37);  3- (4-fluorophenyl) - [1,2,4] triazolo [4,3-a] pyridine-8-carboxylic acid heptamethylene id (1-1-38);  N- {3- (4-φτophenyl) - [l, 2,4] τ-diazol [4,3-a] pyridine-8-carbonyl} -3,5-di ^ 4 eti Jli [иiIepidi] I (I- 1-39 ); N- {3- (4-methoxy) - [l, 2,4] τrazole [4 _! 3-a] I-pyridine-8-carbonyl} -4-hydroxy-4- (4-chlorophenyl) piperidine (1-1-40);  - {3- (4-fluorophenyl) - [1,2,4] triazolo [4,3-a] pyridin-8-carbonyl} -4-benzyl piperidine (1-1- 41);  - {3- (4-φτophenyl) - [l, 2,4] τ-diazol [4,3-a] pyridine-8-aponyl} -l, 2,3,4-τeparidopoxinoJιιιι (11-42);  T - {3- (4-fluorophenyl) - [1,2,4] triazolo [4,3-a] pyridin-8-carbonyl} -4-hydroxy-4- (4-chlorophenyl) piperidine (1-1 -43);  3-phenyl- [1,2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methyl4-chloro-phenyl id (1-1-44)  3- (4-methoxyphenyl) - [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-yaftylamide (L-47);  3- (4-methoxyphenyl) - [1,2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-propylamide (1-1-48);  3- (2-methoxyphenyl) -5-methoxy- [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 2-methylphenyl id (1-1-49);  3- (2-ethoxyphenyl) -5-methoxy- [1, 2,4] triazolo [4,3-a | pyridin-8-carboxylic acid 2-fluorophenylamide (1-1-50);  3- (2-methoxyphenyl) -5-methoxy- [1, 2,4] triazolo [4,3-a] pyridine-8-carboxylic acid 3-methylphenylamide (1-1-51); 3- (2-fluorophenyl) -5-ethoxy- [1.2,4] triazolo [4,3-a] pyridine-8-carboxylic acid (furan-2-yl) methylamide (1-1-52); - {3- (2-methoxyphenyl) -5-methoxy- [1,2,4] triazolo [4,3-a] pyridin-8-carbonyl} piperazine (1-1-53);  N- {3- (2-methoxyphenyl) -5-methoxy- [l, 2,4] thiazole [4,3-a] pyridine-8-aponyl} - '- methylpiperazine (1-1-54);  - {3- (2-methoxy) -5-metho [l, 2,4] tyrazole [4,3-a] pyridine-8-carbone} -2-hydroxyethylamine (1-1-55);  8 - [(2-ethoxybenzoyl) amino] -3-cyclobutyl- [1, 2,4] triazolo [4,3-a] pyridine (1-2-01); 8 - {[(2-methoxyphenyl) acetyl] amino} -3-cy lobutyl- [1, 2,4] triazolo [4,3-a | pyridine (G-2-02);  8 - [(thien-3-yl) acetylamino] -3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-03); 8 - [(2-chloro-5-methylthio-benzoyl) amino] -3-cyclobutyl- [1, 2,4] triazolo | 4,3-a] pyridine (1-2-04);  8 - [(thien-3-yl) carbonyl ino] -3-cyclobutyl- [1, 2,4] triazolo [4,3-a] pyridine (1-2-05); 8 - [(3-methylthien-2-yl) arbonylamino] -3-cy lobutyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-06);  8 - [(indol-2-yl) arbonylamino] -3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridip (1-2-07); 8 - [(3-fluoro-4-methoxybenzoyl) amino] -3-cyclobutyl- [1, 2,4] triazolo [4,3-a] pyridine (1-2-08);  8 - [(2,3-dihydrobenzo [1, 4] dioxin-2-yl) carbonyl ino] -3-cyclobutyl- | 1, 2,4] triazolo | 4,3-a] pyridine (1-2-09);  8 - [(5-chlorothien-2-yl) carbonylamino] -3-qi lobutyl- [1, 2,4] triazolo [4,3-a | pyridine (1-2-10); 8 - [(3,4-methylenedio si-benzoyl) amino] -3-cy lobutyl- [1,2,4] triazolo | 4,3-a] pyridine (1-2- P);  8 - [(5-methylisoxazol-3-yl) carbonylamino] -3-cy lobutyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-12);  8 - [(2-methoxybenzoyl) amino] -3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-13); 8 - [(2-methoxybenzoyl) amino] -3-cyclopentyl- [1, 2,4] triazolo [4,3-a] pyridine (1-2-14); 8 - [(2-ethoxybenzoyl) amino] -3-cyclopentyl- [1, 2,4] triazolo [4,3-a] pyridia (1-2-15); 8 - [(2-methoxybenzoyl) amino] -3-cyclohexyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-16); 8 - [(2-methoxybenzoyl) amino] -3- (Thl-methylpiperidin-4-yl) - [1,2,4] triazolo [4,3-a | pyridine (1-2-17); 8- (benzoylamino] -3- methylpiperidin-4-yl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-18); 8- (benzoylamino] -3- (2-methoxyphenyl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-19); 8- (2-methoxybenzoylamino] -3- (2-methoxyphenyl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-20); 8- (2 is sibenzoylamino] -3 phenyl- [1,2,4] triazolo [4,3-a] pyridine (1-2-21); 8 - [(2-fluorobenzoyl) amino] -3- (1-methylpiperidin-4-yl) - [1,2,4] triazolo [4,3-a] pyridine (1-2- 22);  8 - [(2-fluorobenzoyl) aino] -3- (1-methylpiperidin-3-yl) - [1,2,4] triazolo [4,3-a | pyridine (1-2- 23);  8 - [(2-methoxybenzoyl) amino] -3- (1-methylpiperidin-3-yl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-24);  8 - [(2-methoxybenzoyl) amino] -3- (pyridin-4-yl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-25); 8 - [(2-methoxybenzoyl) amino] -3- (pyridin-3-yl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-26); 8 - [(2-chlorobenzoyl) amino] -3- (b1-methylpiperidin-4-yl) - [1,2,4] triazolo [4,3-a] pyridine (T-2-27);  8 - [(2-chlorobenzoyl) amino] -3-Y-methylpiperidin-3-yl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-28);  8 - [(2,6-dichlorobenzoyl) amino] -3- (1-methylpiperidin-3-yl) - [1,2,4] triazolo [4,3-a] pyridine (1-2-29);  8 - [(2,6-dimethylbenzoyl) amino] -3 ^ -methylpiperidium-3-yl) - [1,2,4] triazolo | 4,3-a] pyridine n (1-2-30);  1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (3,4-dimethoxyphenyl) urea (1-3-01);  1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (2-methoxy-5-methylphenyl) - urea (1-3-02) ;  1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (3,4-ethylenedioxyphenyl) urea (1-3-03); 1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (2-phenylethyl) urea (1-3-04); 1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (3,4-methylenedioxyphenyl) urea (1-3-05); 1- (3-qi lobutyl- [1,2,4] triazolo4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) urea (1-3-06);  1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (tetrahydrofuryl-2-methyl) urea (1-3-07);  1- (3-cy lobutyl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (2-methoxycarbonylthienyl-3) - urea (1-3-08);  1- (3-cyclobutyl- [1, 2,4] triazolo | 4,3-a] pyridin-8-yl) -3- (3-acetylphenyl) urea (1-3-09);  1- (3-cyclobutyl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (4-methoxy-2-methylphenyl) - urea (1-3-10) ;  1- (3-cy lobutyl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (4-methoxy-3-fluorophenyl) urea (Ι-3-P) ;  1- (3-cyclopentyl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) urea (1-3- 12) ;  1- (3-cyclo-sil- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) -urea (1-3- 13) ;  1- {3- (TM-methylpiperidin-4-yl) [1, 2,4] triazolo | 4,3-a] pyridin-8-yl} -3- (furyl-2-methyl) - urea (1- 3-14);  1- {3- (1M-methylpiperidin-3-yl) [1,2,4] triazolo [4,3-a] pyridin-8-yl} -3- (furyl-2-methyl) - urea (1- 3-15);  1- {3- (] methylpiperidin-4-yl) [1,2,4] triazolo [4,3-a] pyridin-8-yl} -3- (2-methoxyphenyl) urea (1-3- 16);  ] - {3- (1-methylpiperidium-4-yl) [1, 2,4] triazolo [4,3-a] pyridin-8-yl} -3- (3,4-dimetho-siphenyl) -urea (1 -3-17);  1- {3-0 ^ -methylpiperidin-3-yl) [1,2,4] triazolo [4,3-a] pyridin-8-yl} -3- (2-ethoxypheyl) - urea (1-3- eighteen);  1- {3- (1-methylpiperidin-3-yl) [1,2,4] triazolo [4,3-a] pyridin-8-yl} -3- (3,4-dimethoxyphenyl) urea (1- 3-19); ] - (3-pyrid-4-yl- [1,2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) -urea (1-3-20 ); ] - (3-pyrid-4-yl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) -urea (1-3-22 ); 1 - (3-pyrid-3-yl- [1, 2,4] triazolo [4,3-a] pyridin-8-yl) -3- (furyl-2-methyl) urea (1-3-23 ); 1 - {3- (-methylpiperidin-4-yl) [1, 2,4] triazolo [4,3-a] pyridin-8-yl} -3-allylurea (1-3- 24); or  1- {3 - ^ - methylpiperidin-3-yl) [1, 2,4] triazolo [4,3-a] pyridin-8-yl} -3-allylurea (1-3- 25). 4. The method of obtaining [1, 2,4] triazolo [4,3-a] pyridines of the general formulas 1-2 or 1-3,

 where R2, R4, R6 and B have the above meanings, X = CI. consisting in sequential cyclocondensation of the B-C (OMe) ₃ orthoester with the L2 compound obtained by the reaction of 2-chloro-3-nitropyridine L with hydrazine; reduction of nitropyridine L3 with hydrogen over palladium on charcoal; acylating the resulting amine b4 with a suitable acyl halide in the presence of a strong base to give compound 1-2, or reacting the amine b4 with a suitable isocyanate in a neutral solvent to give compounds T-3.  5. The active component having the property of an antagonist of A2A receptors, which is a compound of General formula I according to any one of paragraphs 1-3. 6. The active component, which has the properties of a selective antagonist of A2A receptors, to obtain a drug suitable for the prevention and treatment of disorders of the central nervous system, neurodegenerative, inflammatory, oncological diseases, which is a compound of General formula I according to any one of paragraphs 1-3.  7. A pharmaceutical composition having antagonistic activity with respect to the adenosine A2A receptor, comprising, as an active component or compound of general formula I according to any one of claims 1 to 3, or pharmaceutically acceptable salts thereof in a therapeutically effective amount.  8. The pharmaceutical composition according to claim 7 in the form of tablets, capsules and injections, ointments, gels and other finished forms, placed in a pharmaceutically acceptable package.  9. A method of obtaining a pharmaceutical composition according to any one of paragraphs 7-8 by mixing with an inert excipient, auxiliary agent, carrier and / or solvent of at least one active component (substance) of the general formula I according to claims 1 to 3 or its pharmaceutically acceptable salt in a therapeutically effective amount.  10. A method for the selective inhibition of the activity of an adenosine A2A receptor, which consists in the action of an active component (substance) of the general formula G as claimed in claims 1 to 3 or a pharmaceutically acceptable salt thereof on biological objects or samples whose functions are regulated by A2A adenosine receptors.  11. A drug suitable for the prevention and treatment of disorders of the central nervous system, neurodegenerative, inflammatory, oncological diseases, which contains the active component according to claim 6 of the general formula I or the pharmaceutical composition according to claim 7 in a therapeutically effective amount.  12. The drug, according to p. 1 1 in the form of tablets, capsules or injections, placed in a pharmaceutically acceptable package.