WO2012150369A1 - Phosphodiesterase-7-inhibiting heterocyclic derivatives - Google Patents

Abstract

The present invention provides a novel series of compounds of general formula (I) and (II) belonging to a wide family of heterocyclic derivatives that exhibit activity for treating diseases in which PDE7 inhibition is therapeutic, preferably for inflammatory, autoimmune and neurodegenerative diseases. The invention also relates to heterocyclic compounds, and to the method for the production thereof, said compounds being widely applicable as drugs or drug candidates.

Description

 PHOSPHODIESTERASE INHIBITING HETEROCICLICAL DERIVATIVES 7

The present invention relates to heterocyclic derivatives and their potential for the treatment of neurodegenerative and / or neurological diseases, as well as diseases with a systemic and / or central inflammatory component. Therefore, the invention is framed in the pharmaceutical sector.

STATE OF THE TECHNIQUE The enzymatic activity of phosphodiesterases (PDEs) consists in the degradation of cyclic nucleotides (cAMP and cGMP) by hydrolytic breakage of the 3'-phosphodiester bond, giving rise to the corresponding inactive form 5'-monophosphate. CAMP and cGMP are generated by the action of adenylate cyclase and guanylate cyclase respectively, acting as second messengers in transduction of intracellular signals. One way to increase the intracellular levels of cAMP or cGMP is by inhibiting PDEs, since they are their only degradation pathway. The interest in developing specific PDEs inhibitors is based on the anti-inflammatory and immunosuppressive properties shown by agents capable of increasing intracellular cAMP levels. Therefore, selective inhibitors of cAMP-specific PDEs may be of interest as a therapy for the treatment of different diseases [Lugnier, C. Cyclic nucleotide phosphodiesterase (PDE) superfamily: A new target for the development of specific therapeutic agents. Pharmacol Ther. 2006, 109, 366-398], mainly immune system disorders, such as multiple sclerosis, inflammatory disorders and central nervous system (CNS) disorders [Menniti FS, Faraci WS, Schmidt CJ Phosphodiesterases in the CNS: targets for drug development . Nat. Rev. Drug Discov. 2006, 5, 660-670]. Since virtually all PDEs are expressed in the CNS, there is an increase in function in many pathologies, PDEs inhibitors could also be considered as promising drugs for the treatment of psychiatric and neurodegenerative diseases [Brandon, NJ; Rotella, D. P. Potential CNS applications for PDEs inhibitors. Ann. Rep. Med. Chem. 2007, 42, 3-12].

Thus, for example, cilostazol, a selective PDE3 inhibitor, has been seen to reduce cell death after a cerebral infarction and also promotes the survival of axotomized retinal ganglion cells. Sildenafil, a PDE5 inhibitor, could improve learning by modulating the transduction of NO-cGMP signals, a pathway involved in cognitive decline due to age and neurodegenerative diseases. On the other hand, selective PDE10A inhibitors are potent antipsychotic agents capable of improving the cognitive symptoms of schizophrenia and PDE4 inhibitors represent a good approximation for the treatment of memory disorders. Among the 1 1 isoenzymes identified from PDEs, PDE7 is an enzyme specific for cAMP, insensitive to Rolipram (PDE4 inhibitor), which is expressed in different areas of the brain, in addition to lymphocytes [Li, L; Yee, C; Beavo, JA CD3-and CD28-dependent induction of PDE7 required for T cell activation. Science 1999, 283, 848-851; Nakata, A .; Ogawa, K .; Sasaki, T .; Koyama, N .; Wada, K .; Kotera, J .; Kikkawa, H .; Omori, K .; Kaminuma, O. Potential role of phosphodiesterase 7 in human T cell function: comparative effects of two phosphodiesterase inhibitors. Clin. Exp. Immunol. 2002, 128, 460-466] and their inhibitors have allowed the start of the study of their physiology and pathology [Gil, C; Campillo, NE; Pérez, DI; Martínez, A. Phosphodiesterase 7 (PDE7) inhibitors as new drugs for neurological and anti-inflammatory disorders. Exp. Opin. Ther. Patents 2008, 18, 1 127-1 139]. Thus, it has been observed that the selective PDE7 inhibitor, BRL-50481, does not decrease the proliferation of T cells per se, however, it does synergistically increase the effect of the Rolipram PDE4 inhibitor on the elevation of the levels of CAMP. Although the efficacy of PDE7 inhibitors has recently been demonstrated in Parkinson's animal models [Morales-García, J .; Round, M .; Gil, C; Alonso-Gil, S .; Martínez, A .; Santos, A .; Perez-Castillo, A. "Phosphodiesterase 7 inhibition preserves dopaminergic neurons in cellular and rodent models of Parkinson's disease ". PLoS ONE. 2011, 6, e17240] and spinal cord damage [Paterniti;!.; Mazzon, E.; Gil, C; Impllizzari, D .; Palomo, V .; Redondo, M .; Pérez, DI; Esposito, E .; Martínez, A .; Cuzzocrea, S. "PDE 7 inhibitors: new potential drugs for the therapy of spinal cord injury". PLoS ONE. 2011, 6, e15937 ], however, it is necessary to develop new molecules that validate their pharmacological effects both in vitro and in vivo.

DETAILED DESCRIPTION OF THE INVENTION

The present invention provides, on the one hand, a new series of compounds belonging to a broad family of heterocyclic derivatives with activity in PDE7 and on the other the use of this broad family of heterocyclic derivatives for the treatment of diseases where PDE7 inhibition is therapeutic. . Preferably for inflammatory, autoimmune and neurodegenerative diseases. On the other hand, heterocyclic compounds are described, as well as their method of obtaining them, being able to have a great application as drugs or drug candidates. Therefore, a first aspect of the present invention relates to a compound of formula (I) or a tautomer, salt, solvate or prodrug thereof.

(I) where

each Ri and R2 are the same or different and are independently selected from hydrogen, a substituted or unsubstituted C1-C4 alkyl group, a halogen group, a substituted or unsubstituted C1-C4 haloalkyl group, a nitro group, a -OR ₃ group wherein R ₃ is selected from hydrogen or a substituted or unsubstituted C1-C4 alkyl group or a group -NR4R ₅ - where R4 and R5 are the same or different and independently selected from H or a C1-C5 alkyl group; X is selected from a group -C = 0, a group -C = S, -O-, a group -

NR6- or a group -R ₇ -X 'where R6 is selected from hydrogen or a substituted or unsubstituted C1-C3 alkyl group, where R ₇ is selected from a substituted or unsubstituted C1-C4 alkyl group or a C2 alkenyl group -C4 substituted or unsubstituted and X 'is selected from a group -C = 0, a group -C = S, -O- or a group -NR ₆ -;

Y is selected from a group -C = 0, a group -C = S, -O- a group - NR ₆ - or a group Y'-Re-, where Y 'is selected from a group -C = 0, a group -C = S, -O-, a group -NR ₆ - and Rs is selected from a substituted or unsubstituted C1-C4 alkyl group or a substituted or unsubstituted C2-C4 alkenyl group;

Q is selected from -O-, -S-, or -NR ₉ , where Rg is selected from hydrogen or a substituted or unsubstituted C1-C3 alkyl group,

n and m are the same or different and independently select from an integer selected from 1, 2, 3, 4 and 5 with the proviso that the following compounds:

 - (5- (2,4-dichorophenyl) furan-2-yl) methyl-3,4,5-triethoxybenzoate.

 - (5- (2,3-dichlorophenyl) furan-2-yl) methyl-3,4,5-triethoxybenzoate

 - (5- (2-Methyl-4-nitrophenyl) furan-2-yl) methyl-3,4,5-triethoxybenzoate

 - (5- (3-Chloro-4-methoxyphenyl) furan-2-yl) methyl-3,4,5-triethoxybenzoate

- N - ((5- (4-bromophenyl) furan-2-yl) methyl) -3,4,5-triethoxybenzamide - (5- (2,3-dichlorophenyl) furan-2-yl) methyl-3,4,5-trimethoxybenzoate

 - (5- (3-Chloro-4-methoxyphenyl) furan-2-yl) methyl-3,4,5-trimethoxybenzoate

 - N - ((5- (4-fluorophenyl) furan-2-yl) methyl) -3,4,5-trimethoxybenzamide

 - N - ((5- (2,4-dichlorophenyl) furan-2-yl) methyl) -3,4,5-trimethoxybenzamide

 - N - ((5- (4-chlorophenyl) furan-2-yl) methyl) -3,4,5-trimethoxybenzamide

 - N - ((5- (4-bromophenyl) furan-2-yl) methyl) -3,4,5-trimethoxybenzamide

 - N - ((5- (4-bromophenyl) furan-2-yl) methyl) -3,4,5-trimethoxy-2-nitrobenzamide

- 3,4,5-trimethoxy-N - ((5-phenylthiophene-2-yl) methyl) benzamide

 - 5- (2-fluorophenyl) -N- (3,4,5-trimethoxybenzyl) -2-furancarboxamide

 - 5- (2-fluorophenyl) -N- (1 - (3,4,5-trimethoxyphenyl) ethyl) -2-furancarboxamide

- 5- (2-fluorophenyl) -N- (1 - (3,4,5-trimethoxyphenyl) ethyl) -2-thiophenecarboxamide

- 5- (4-chlorophenyl) -N- (3,4,5-trimethoxybenzyl) -2-thiophenecarboxamide

 - 5- (2-chlorophenyl) -N- (3,4,5-trimethoxybenzyl) -2-furancarboxamide

 are not included in the formula (I).

According to a preferred embodiment each Ri is the same or different and is independently selected from hydrogen or a -OR3 group wherein R3 is selected from hydrogen or a substituted or unsubstituted C1-C4 alkyl group. According to another preferred embodiment, n is 3.

According to another preferred embodiment, each R2 is the same or different and is independently selected from hydrogen, a nitro group, a substituted or unsubstituted C1-C2 alkyl group, a C1-C4 haloalkyl _, chlorine, fluorine, bromine or a group - OR3 in where R3 is selected from hydrogen or a substituted or unsubstituted C1-C4 alkyl group.

According to another preferred embodiment, m is an integer selected from 1 to 2.

Another preferred embodiment comprises the compound of general formula (I), which is selected from the following list: -3, 5- (4-Nitrophenyl) -2-furylmethyl 4,5-triethoxybenzoate (MR 1 .44)

-3,4,5-5- (4-methylphenyl) -2-furylmethyl triethoxybenzoate (MR 1 .61):

-3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate (MR 1 .62):

-3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate (MR 2.50):

-3,4,5-5- (2,4-dichlorophenyl) -2-furylmethyl trimethoxybenzoate (MR 2.51):

-5- (2,4,5-Dichlorophenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .48):

-5- (4,5-methylphenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .50):

3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate (MR 1 .51):

-5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .52):

-5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate (MR 2.20):

-5- (3,4,5-Trimethoxybenzyl-2-trifluoromethylphenyl) -2-furoate (MR 2.21):

-5- (2-nitro-4-methylphenyl) -2,4,5-trimethoxybenzyl furoate (MR 2.24):

-5- (3,4,5-Trimethoxybenzyl-3-trifluoromethylphenyl) -2-furoate (MR 2.30):

-5- (4,5-methoxyphenyl) -2,4,5-trimethoxybenzyl furoate (MR 2.31):

-5- (3,4,5-Trimethoxybenzyl-2-chloro-5-trifluoromethylphenyl) -2-furoate (MR 2.32): -5- (3,4,5-triethoxybenzyl (4,5-methylphenyl) -2-furoate ( MR 1 .57):

3,4,5-Triethoxybenzyl-5-phenyl-2-furoate (MR 1 .58):

-5- (4-nitrophenyl) -2,4,5-triethoxybenzyl furoate (MR 1.59):

-5- (2,4,5-Dichlorophenyl) -2,4,5-triethoxybenzyl furoate (MR 1 .60):

-N- (3,4,5-trimethoxybenzyl) -5- (2-trifluoromethylphenyl) -2-furamide (MR 2.35):

-A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide (MR 2.36):

-A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-chlorophenyl) -2-furamide (MR 3.13):

3,4,5-Trimethoxybenzyl-5-phenyl-2-thiophenecarboxylate (MR 2.39): or a tautomer, salt, solvate or prodrug thereof.

Preferably, the compound of general formula (I) is selected from the following list -3,4,5-5- (4-nitrophenyl) -2-furylmethyl triethoxybenzoate (MR 1 .44)

-3,4,5-5- (4-methylphenyl) -2-furylmethyl triethoxybenzoate (MR 1 .61):

-3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate (MR 1 .62): -3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate (MR 2.50):

-3,4,5-5- (2,4-dichlorophenyl) -2-furylmethyl trimethoxybenzoate (MR 2.51):

-5- (2,4,5-Dichlorophenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .48):

-5- (4,5-methylphenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .50):

3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate (MR 1 .51):

 -5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .52):

-5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate (MR 2.20):

-5- (3,4,5-Trimethoxybenzyl-2-trifluoromethylphenyl) -2-furoate (MR 2.21):

-5- (2-nitro-4-methylphenyl) -2,4,5-trimethoxybenzyl furoate (MR 2.24):

-5- (3,4,5-Trimethoxybenzyl-3-trifluoromethylphenyl) -2-furoate (MR 2.30):

-5- (4,5-methoxyphenyl) -2,4,5-trimethoxybenzyl furoate (MR 2.31):

-5- (4,5-methylphenyl) -2,4,5-triethoxybenzyl furoate (MR 1 .57):

3,4,5-Triethoxybenzyl-5-phenyl-2-furoate (MR 1 .58):

-5- (4-nitrophenyl) -2,4,5-triethoxybenzyl furoate (MR 1.59):

-5- (2,4,5-Dichlorophenyl) -2,4,5-triethoxybenzyl furoate (MR 1 .60):

 -N- (3,4,5-trimethoxybenzyl) -5- (2-trifluoromethylphenyl) -2-furamide (MR 2.35):

-A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide (MR 2.36):

3,4,5-Trimethoxybenzyl-5-phenyl-2-thiophenecarboxylate (MR 2.39): or a tautomer, salt, solvate or prodrug thereof.

Even more preferably the compound of the general formula (I) is selected from the following list -3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate (MR 1 .62):

 -3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate (MR 2.50):

3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate (MR 1 .51):

-5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .52):

-5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate (MR 2.20):

-5- (3,4,5-Trimethoxybenzyl-2-trifluoromethylphenyl) -2-furoate (MR 2.21):

-A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide (MR 2.36): or a tautomer, salt, solvate or prodrug thereof.

A second aspect of the present invention relates to a pharmaceutical composition comprising a compound of general formula (I) or a tautomer, salt, solvate or prodrug thereof.

(I where

each Ri and _R2 are identical or different and is independently a group selected from hydrogen C1-C4 substituted or unsubstituted, a halogen group, a haloalkyl group C1-C4 substituted or unsubstituted, a nitro group, a group -OR3 wherein R3 is selected from hydrogen or a substituted or unsubstituted C1-C4 alkyl group or a group -NR4R ₅ - where R4 and R ₅ are the same or different and independently selected from H or a C1-C5 alkyl group; X is selected from a group -C = 0, a group -C = S, -O-, a group -

NR ₆ - or a group -R7-X ', where R ₆ is selected from hydrogen or a substituted or unsubstituted C1-C3 alkyl group, where R ₇ is selected from a substituted or unsubstituted C1-C4 alkyl group or a C ₂ -C4 substituted or unsubstituted alkenyl group and X 'is selected from a group -C = 0, a group -C = S, -O- or a group -NR ₆ -; Y is selected from a group -C = 0, a group -C = S, -O- a group - NR ₆ - or a group Y'-Re-, where Y 'is selected from a group -C = 0, a group -C = S, -O-, a group -NR ₆ - and Rs is selected from a substituted or unsubstituted C1-C4 alkyl group or a substituted or unsubstituted C2-C4 alkenyl group;

Q is selected from -O-, -S-, or -NR ₉ , where Rg is selected from hydrogen or a substituted or unsubstituted C1-C3 alkyl group,

n and m are the same or different and independently select from an integer selected from 1, 2, 3, 4 and 5 and at least one pharmaceutically acceptable carrier, adjuvant and / or vehicle.

According to a preferred embodiment each R1 is the same or different and is independently selected from hydrogen or a -OR3 group wherein R3 is selected from hydrogen or a substituted or unsubstituted C1-C4 alkyl group.

According to another preferred embodiment n is 3. According to another preferred embodiment, each R2 is the same or different and is independently selected from hydrogen, a nitro group, a substituted or unsubstituted C1-C2 alkyl group, a C1-C4 haloalkyl group _, chlorine, fluorine, bromine or a -OR3 group wherein R ₃ is selected from hydrogen, or a substituted or unsubstituted C4 alkyl group.

According to another preferred embodiment, m is an integer selected from 1 to 2.

Another preferred embodiment comprises that the pharmaceutical composition which in turn comprises the compound of general formula (I), which is selected from the following list: -3, 5- (4-Nitrophenyl) -2-furylmethyl 4,5-triethoxybenzoate (MR 1 .44)

-3,4,5-5- (4-methylphenyl) -2-furylmethyl triethoxybenzoate (MR 1 .61):

-3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate (MR 1 .62):

-3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate (MR 2.50):

-3,4,5-5- (2,4-dichlorophenyl) -2-furylmethyl trimethoxybenzoate (MR 2.51):

-5- (2,4,5-Dichlorophenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .48):

-5- (4,5-methylphenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .50):

3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate (MR 1 .51):

-5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .52):

-5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate (MR 2.20):

-5- (3,4,5-Trimethoxybenzyl-2-trifluoromethylphenyl) -2-furoate (MR 2.21):

-5- (2-nitro-4-methylphenyl) -2,4,5-trimethoxybenzyl furoate (MR 2.24):

-5- (3,4,5-Trimethoxybenzyl-3-trifluoromethylphenyl) -2-furoate (MR 2.30):

-5- (4,5-methoxyphenyl) -2,4,5-trimethoxybenzyl furoate (MR 2.31):

-5- (3,4,5-Trimethoxybenzyl-2-chloro-5-trifluoromethylphenyl) -2-furoate (MR 2.32): -5- (3,4,5-triethoxybenzyl (4-methylphenyl) -2-furoate ( MR 1 .57):

3,4,5-Triethoxybenzyl-5-phenyl-2-furoate (MR 1 .58):

-5- (4-nitrophenyl) -2,4,5-triethoxybenzyl furoate (MR 1.59):

-5- (2,4,5-Dichlorophenyl) -2,4,5-triethoxybenzyl furoate (MR 1 .60):

-N- (3,4,5-trimethoxybenzyl) -5- (2-trifluoromethylphenyl) -2-furamide (MR 2.35):

-A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide (MR 2.36):

-A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-chlorophenyl) -2-furamide (MR 3.13):

3,4,5-Trimethoxybenzyl-5-phenyl-2-thiophenecarboxylate (MR 2.39): More preferably the compound of general formula (I) is selected from the following list:

-3,4,5-5- (4-nitrophenyl) -2-furylmethyl triethoxybenzoate (MR 1.44)

-3,4,5-5- (4-methylphenyl) -2-furylmethyl triethoxybenzoate (MR 1 .61):

-3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate (MR 1 .62):

 -3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate (MR 2.50):

-3,4,5-5- (2,4-dichlorophenyl) -2-furylmethyl trimethoxybenzoate (MR 2.51): -5- (2,4,5-Dichlorophenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .48):

-5- (4,5-methylphenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .50):

3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate (MR 1 .51):

-5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .52):

-5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate (MR 2.20):

-5- (3,4,5-Trimethoxybenzyl-2-trifluoromethylphenyl) -2-furoate (MR 2.21):

-5- (2-nitro-4-methylphenyl) -2,4,5-trimethoxybenzyl furoate (MR 2.24):

-5- (3,4,5-Trimethoxybenzyl-3-trifluoromethylphenyl) -2-furoate (MR 2.30):

-5- (4,5-methoxyphenyl) -2,4,5-trimethoxybenzyl furoate (MR 2.31):

-5- (4,5-methylphenyl) -2,4,5-triethoxybenzyl furoate (MR 1 .57):

3,4,5-Triethoxybenzyl-5-phenyl-2-furoate (MR 1 .58):

-5- (4-nitrophenyl) -2,4,5-triethoxybenzyl furoate (MR 1.59):

-5- (2,4,5-Dichlorophenyl) -2,4,5-triethoxybenzyl furoate (MR 1 .60):

-N- (3,4,5-trimethoxybenzyl) -5- (2-trifluoromethylphenyl) -2-furamide (MR 2.35):

-A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide (MR 2.36):

3,4,5-Trimethoxybenzyl-5-phenyl-2-thiophenecarboxylate (MR 2.39):

Even more preferably the compound of general formula (I) is selected from the following list:

-3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate (MR 1 .62):

-3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate (MR 2.50):

3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate (MR 1 .51):

-5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate (MR 1 .52):

-5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate (MR 2.20):

-5- (3,4,5-Trimethoxybenzyl-2-trifluoromethylphenyl) -2-furoate (MR 2.21):

-A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide (MR 2.36):

A third aspect of the present invention relates to the use of a compound of general formula (I), or a tautomer, salt, solvate or prodrug thereof, as defined above in the second aspect of the present invention, for the preparation of a medicine A fourth aspect of the present invention relates to the use of the compound of general formula (I), or a tautomer, salt, solvate or prodrug thereof, as defined above in the second aspect of the present invention, for the preparation of a medication for the treatment and / or prophylaxis of:

- inflammatory and / or autoimmune pathologies selected from the following list: inflammatory bowel disease, inflammatory joint pathologies, atopic dermatitis and other inflammatory dermatological pathologies, neuritis, encephalitis, encephalomyelitis and inflammatory pathologies that affect the central nervous system such as multiple sclerosis, or peripheral , myositis, vasculitis, systemic lupus erythematosus, asthma, chronic obstructive pulmonary disease, infectious diseases that occur with inflammation, host rejection reactions against grafting, inflammation associated with spinal cord injury, conjunctivitis and inflammatory oculopathies, otitis and mucositis. - neurodegenerative and / or neurological pathologies selected from the following list: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, cerebral ischemia, post-encephalitic parkinsonisms, dystonia, Tourette's syndrome, periodic limbic movement pathologies, restless legs syndrome and attention deficit hyperactivity disorders.

- pathologies that occur with movement disorders.

A fifth aspect of the present invention relates to a compound of general formula (II)) or a tautomer, salt, solvate or prodrug thereof:

where

each Ri is the same or different and is independently selected from hydrogen, a substituted or unsubstituted C1-C4 alkyl group, a halogen group, a substituted or unsubstituted C1-C4 haloalkyl group, a nitro group, an OR3 group wherein R3 is selected from hydrogen or an alkyl group C1-C4 substituted or unsubstituted or -NR4R ₅ group - wherein R4 and R5 are identical or different and is independently selected from H or Ci- C ₅ alkyl;

X is selected from a group -C = 0, a group -C = S, -O-, a group - NR ₆ - or a group -R7-X ', where R6 is selected from hydrogen or a C1-C3 alkyl group substituted or unsubstituted, where R ₇ is selected from a substituted or unsubstituted C1-C4 alkyl group or a substituted or unsubstituted C ₂ -C ₄ alkenyl group and X 'is selected from a group -C = 0, a group - C = S, -O- or a group -NR ₆ -;

Y is selected from a group -C = 0, a group -C = S, -O- a group - NR ₆ - or a group Y'-Re-, where Y 'is selected from a group -C = 0, a -C = S group, -O-, -NR ₆ group one - and Rs is selected from a C1-C4 substituted or unsubstituted alkenyl group or C ₂ -C 4 substituted or unsubstituted;

Q is selected from -O-, -S-, or -NR ₉ , where Rg is selected from hydrogen or a substituted or unsubstituted C1-C3 alkyl group.

K is selected from a substituted or unsubstituted C1-C4 alkyl group, hydrogen or a halogen. If the alkyl group is substituted, it will be at least one hydroxyl group. n is an integer selected from 1, 2, 3, 4 and 5

According to a preferred embodiment each Ri is the same or different and is independently selected from hydrogen or a -OR3 group wherein R3 is selected from hydrogen or a substituted or unsubstituted C1-C4 alkyl group.

According to another preferred embodiment, n is 3.

According to another preferred embodiment K is hydrogen

According to another preferred embodiment K is a halogen.

 According to another preferred embodiment K is a substituted alkyl group.

According to another preferred embodiment the compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof is selected from the following list:

- 5- (2,4-Dichlorophenyl) -2-Furyl Methanol (MR 1 .32)

 - 3,4,5-Trimethoxybenzyl 2-furoate (MR 2.38)

 - 3,4,5-Trimethoxybenzyl 5-bromo-2-thiophenecarboxylate (MR 2.37)

 - A / - (3,4,5-trimethoxybenzyl) -5-bromo-2-thiophenecarboxamide (MR 2.43)

More preferably, the compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof is selected from the following list:

- 5- (2,4-Dichlorophenyl) -2-Furyl Methanol (MR 1 .32)

 - 3,4,5-Trimethoxybenzyl 2-furoate (MR 2.38)

Even more preferably, the compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof is 5- (2,4-dichlorophenyl) -2-furyl methanol (MR 1 .32). In the present invention the compounds of general formula (II) are used as reaction intermediates in order to synthesize the compounds of general formula (I) described in the present invention. Further in the present invention, some of the compounds of the general formula (II) have the same activity as the compounds of the general formula (I). A sixth aspect of the present invention relates to a pharmaceutical composition comprising the compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof, according to any one of claims 24 to 32 and at least one carrier, adjuvant and / or pharmaceutically acceptable vehicle.

A seventh aspect of the present invention relates to the use of the compound of formula (II) or a tautomer, salt, solvate or prodrug thereof, as defined above, which is selected from the following list:

- 5- (2,4-Dichlorophenyl) -2-Furyl Methanol (MR 1 .32)

- 3,4,5-Trimethoxybenzyl 2-furoate (MR 2.38) for the preparation of a medicine.

An eighth aspect of the present invention relates to the use of the compound of general formula (II), or a tautomer, salt, solvate or prodrug thereof, as defined above, which is selected from the following list:

- 5- (2,4-Dichlorophenyl) -2-Furyl Methanol (MR 1 .32)

- 3,4,5-Trimethoxybenzyl 2-furoate (MR 2.38) for the preparation of a medicine for the treatment and / or prophylaxis of pathologies: inflammatory, autoimmune, neurodegenerative, neurological and / or movement disorders. - inflammatory and / or autoimmune selected from the following list: inflammatory bowel disease, inflammatory joint pathologies, atopic dermatitis and other inflammatory dermatological pathologies, neuritis, encephalitis, Encephalomyelitis and inflammatory pathologies that affect the central nervous system such as multiple or peripheral sclerosis, myositis, vasculitis, systemic lupus erythematosus, asthma, chronic obstructive pulmonary disease, infectious diseases that occur with inflammation, host rejection reactions against grafting, associated inflammation to spinal cord injury, conjunctivitis and inflammatory oculopathies, otitis and mucositis.

- neurodegenerative and / or neurological selected from the following list: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, cerebral ischemia, post-encephalitic parkinsonisms, dystonia, Tourette's syndrome, periodic limbic movement pathologies, restless legs syndrome and disorders of attention deficit hyperactivity disorder. - they are involved with movement disorders.

In the present invention the term "alkyl" preferably comprises branched and unbranched alkyls such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, sec-butyl, and their corresponding isomers

The term "alkenyl" preferably comprises branched and unbranched alkenyls, for example vinyl, propen-1-yl, propen-2-yl, but-1-en-1-yl, but-1-en-2-yl, but- 2-en-1-yl, but-2-en-2-yl, but-1-en-3-yl, 2-methyl-prop-2-en-1-yl, or 2- methyl-prop-1 -en-1-yl and its corresponding isomers.

The term "C1-C4" is used in relation to the text for example in the context of the definition "C ₁ -C ₄ alkyl", as the group of alkyls having a finite number of carbon atoms from 1 to 4, that is 1, 2, 3 or 4 carbon atoms. The term "Ci-C ₄ " is interpreted as any sub-interval between Ci-C ₄ , C2-C3, C1-C2, C1-C3, C2-C ₄ , C3-C ₄ . In the same way the term "C1-C3" is used in relation to the text for example in the context of the definition "C1-C3 alkyl", as the group of alkyls having a finite number of carbon atoms from 1 to 3, that is 1, 2 or 3 carbon atoms. The term "C1-C3" is interpreted as any sub-interval between C1-C3, CrC ₂ , C ₂ -C ₃ .

In the same way the term "Ci-C ₂ " is used in reference to the text for example in the context of the definition "CrC ₂ alkyl", as the group of alkyls having a finite number of carbon atoms from 1 to 2, that is 1 or 2 carbon atoms.

In the same way the term used as "C ₂ -C4" is used in relation to the text for example in the context of the definitions "C ₂ -C ₄ alkenyl", they are understood as alkenyl groups with a finite number of atoms of 2 to 4 carbon, that is 2, 3 or 4 carbon atoms. It is understood that the term "C ₂ - C ₄ " implies any sub-interval between. C ₂ -C ₄ , C ₂ -C3, C3-C ₄

In the present invention, the term haloalkyl preferably comprises branched and unbranched alkyls such as methyl, ethyl, n-propyl, iso-propyl, n-butyl, iso-butyl, tert-butyl, sec-butyl, and their corresponding isomers , which at least have a substitution by a halogen.

By "halogen" is meant in the present invention a bromine, chlorine, iodine or fluorine atom.

The present invention also comprises the isomers, constitutional isomers and stereoisomers of the compounds of formula (I).

The term isomers is understood as chemical compounds with the same number and type of atoms as another chemical species. There are two large classes of isomers, constitutional isomers and stereoisomers. The term constitutional isomers is understood as having a chemical meaning where chemical compounds have the same number and type of atoms but are connected by different sequences. These are functional isomers, structural isomers, tautomers or valence isomers.

Stereoisomers are those that have their atoms connected sequentially in the same way, so the two condensed formulas of the isomers are identical. Isomers differ in the way atoms are oriented in space. There are two large subclasses of stereoisomers; conformational, which can be interconverted by rotation of simple and configurational links, which cannot be interconverted.

In the configurational isomers are enantiomers and diastereomers. The enantiomers that are related to others since they are like the images of a mirror from now on mirror image. Enantiomers must contain some number of stereogenic centers, and each stereocenter is the mirror image that corresponds to the center of the other molecule. If one or more of these centers differs in configuration, the two molecules are not mirror images. Stereoisomers that are not enantiomers are called diastereomers or diastereomers.

In the present invention the term "pharmaceutical composition" refers to a set of components that is formed at least by the compound of formula (I) of the invention, which has at least one application in the improvement of physical or physiological or psychological well-being. of a subject, which implies an improvement of the general state of his health, for example a cosmetic application, although it may not imply a physiological effect on the organism but an improvement in the well-being of the subject related to his psychology. Therefore, said pharmaceutical composition may be the basis for the preparation of a medicament. The term "medicament" has a more limited meaning than the meaning of "pharmaceutical composition", as defined in the present invention, since the medicament necessarily implies a therapeutic effect, that is, a physiological effect on the subject's metabolism.

The medicament referred to in the present invention can be for human or veterinary use. The "medicine for human use" is any substance or combination of substances that is presented as having properties for the treatment and / or prophylaxis of diseases in humans or that can be used in humans or administered to humans in order to restore , correct or modify physiological functions by exercising a pharmacological, immunological or metabolic action, or establishing a medical diagnosis. The "veterinary medicinal product" is any substance or combination of substances that is presented as having curative and / or preventive properties with respect to animal diseases or that can be administered to the animal in order to restore, correct or modify its physiological functions exercising a pharmacological, immunological or metabolic action, or establishing a veterinary diagnosis. "Premixes for medicated feedingstuffs" - prepared to be incorporated into a feed will also be considered "veterinary drugs".

The term "excipient" refers to a substance that helps the absorption of the extract of the invention, stabilizes said extract or aids in the preparation of the medicine in the sense of giving it consistency or providing flavors that make it more pleasant. Thus, the excipients could have the function of keeping the ingredients together such as starches, sugars or cellulose, sweetening function, dye function, drug protection function such as to isolate it from air and / or moisture, function filling a tablet, capsule or any other form of presentation such as dibasic calcium phosphate, a disintegrating function to facilitate the dissolution of the components and their absorption in the intestine, without excluding other types of excipients not mentioned in this paragraph.

The composition of the invention may further comprise a pharmacologically acceptable carrier. In addition, the vehicle must be pharmaceutically acceptable. A "pharmaceutically acceptable carrier" refers to those substances, or combination of substances, known in the pharmaceutical sector, used in the preparation of pharmaceutical forms of administration and includes, but are not limited to, solids, liquids, solvents or surfactants. The vehicle can be an inert substance or action analogous to any of the sequences of the present invention. The function of the vehicle is to facilitate the incorporation of the extract of the invention as well as other compounds, allow a better dosage and administration or give consistency and form to the pharmaceutical composition. When the presentation form is liquid, the vehicle is the diluent. The pharmacologically acceptable carrier could be, but not limited to, a nanoparticle, a liposome, a micelle or a microemulsion.

Pharmaceutically acceptable salts of the compounds of the invention can be prepared by one or more of these procedures:

(i) reacting the compound of the invention with the desired acid

(ii) convert a salt of the compound of the invention into another, by reaction with an appropriate acid or by a suitable ion exchange column. The two reactions are typically carried out in solution. The salt can precipitate in solution and can be collected by filtration or solutions of the compound of the invention and the desired acid or base can be recovered, as appropriate. The salt can be precipitated from a solution and collected by filtration or can be recovered by evaporation of the solvent. The degree of ionization in the salt can vary between completely ionized to almost non-ionized. Pharmaceutically acceptable salt by the addition of acids, refers to those salts that retain the biological effectiveness and properties of free bases, which are not undesirable neither biologically nor otherwise, and which are formed with inorganic acids such as, but not limited to , hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid and the like, and organic acids such as, but not limited to, acetic acid, 2,2-dichloroacetic acid, adipic acid, alginic acid, ascorbic acid, aspartic acid, benzenosulfonic acid, benzoic acid, 4-acetamidobenzoic acid, canphonic acid, camphor-10-sulfonic acid, capric acid, caproic acid, caprylic acid, carbonic acid, cinnamic acid, citric acid, cyclamic acid, dodecylsulfuric acid, ethane-1 acid, 2-disulfonic acid, ethanesulfonic acid, 2- hydroxyethanesulfonic acid, fumaric acid, galactic acid, gentisic acid, glucoheptonic acid, gluconic acid, glucuronic acid, glutamic acid, 2- oxoglutaric acid, glycerophosphoric acid, glycolic acid, hippuric acid, isobutyric acid, lactic acid, lactobionic acid, lauric acid, maleic acid, oleic acid, cerotic acid, oxalic acid, palmitic acid, pamoic acid, propionic acid, pyroglutamic acid, pyruvic acid, salicylic acid, 4- aminosalicylic acid, sebacic acid, stearic acid, succinic acid, tartaric acid, thiocyanic acid, p-toluenesulfonic acid, trifluoroacetic acid, undecylenic acid, and Similar.

Pharmaceutically acceptable salt by addition of bases refers to those salts that retain the biological effectiveness and properties of free acids, which are not undesirable either biologically or otherwise. These salts are prepared from the addition of an inorganic base or an organic base to the free acid. Salts derived from inorganic bases include, but are not limited to, sodium, potassium, lithium, ammonium, calcium, magnesium, iron, zinc, copper, manganese, aluminum and the like. Salts derived from organic bases include, but are not limited to, salts of primary, secondary and tertiary amines; substituted amines that include natural substituted amines, cyclic amines, substituted guanidines and basic ion exchange resins, such as ammonia, isopropylamine, trimethylamine, diethylamine, triethylamine, tripropylamine, diethanolamine, ethanolamine, deanol, 2-methylaminoethanol, 2-diethylaminoethanol, dicyclohexylamine, lysine, arginine, histidine, caffeine, procalna, hydrabamine, choline, betaine, benetamine, benzathine, ethylenediamine, glucamine, ethylamine, glucamine, ethylamine, glucamine, ethylamine, glucamine, ethylamine theobromine, triethanolamine, tromethamine, purines, piperazine, / V-ethylpiperidine, guanidine, polyamine resins and the like.

Throughout the description and the claims the word "comprises" and its variants are not intended to exclude other technical characteristics, additives, components or steps. For those skilled in the art, other objects, advantages and features of the invention will be derived partly from the description and partly from the practice of the invention. The following examples and figures are provided by way of illustration, and are not intended to be limiting of the present invention.

BRIEF DESCRIPTION OF THE FIGURES

Figure 1A) represents the production of nitrites in microglia stimulated with LPS and using different compounds of the invention at 5 and 10 μM (Production of nitrites in microglia stimulated with LPS). Figure 1 B) represents the viability of the microglia in the presence of the different compounds at 5 and 10 μΜ (Cytotoxicity study of the microglia compounds). Figure 2A) represents the production of nitrites in astrocytes stimulated with LPS and using different compounds of the invention at 5 and 10 μM (Production of nitrites in astrocytes stimulated with LPS). Figure 2B) represents the viability of astrocytes in the presence of the different compounds at 5 and 10 μΜ (Cytotoxicity study of compounds in astrocytes). Figure 3 represents the linear correlation between described and experimental permeability of 10 commercial compounds using the PAMPA-Blood-brain Barrier methodology. EXAMPLES OF THE INVENTION

 Abbreviations: DCC: Λ /, Λ / '- dicyclohexylcarbodiimide; DME: 1,2-dimethoxyethane; Pd (0) tetrakis: Palladium (0) -tetrakis (triphenylphosphine); PyBOP: benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate; ASD: triethylamine.

Synthesis of 5- (2,4-dichlorophenyl) -2-furyl methanol (MR 1.32)

Sobre una suspensión de LiAIH₄ (66 mg, 1 .75 mmol) en THF (10 mi) se le añade el ácido 5-(2,4-diclorofenil)-2 furoico (300 mg, 1 .16 mmol) disuelto en THF (5 mi) a 0°C. Se mantiene en agitación y a temperatura ambiente durante 15 minutos. Finalmente, a la mezcla de reacción se le añade agua (2 mi) lentamente a 0^o C y se filtra sobre celita. La mezcla de reacción se extrae con acetato/ agua (30 mi). Rendimiento: sólido amarillo (72 mg, 61 %). ¹ H-RMN (CDCI₃, 300 MHz) δ: 7.81 (d, J = 8.79 Hz, 1 H, H-ar); 7.45 (d, J = 2.20 Hz, 1 H, H-ar); 7.30 (d, J = 8.79 Hz, 1 H, H-ar); 7.07 (d, J= 3.07 Hz, 1 H, H-furil); 6.43 (d, J= 3.51 Hz, 1 H, H-furil); 4.68 (s, 2H, O-Chb-furil). ¹³C-RMN (CDCI₃, 75 MHz) δ: 153.8 (C-furil); 149.3 (C-furil); 133.1 (C-ar); 130.6 (C-ar); 130.4 (C-ar); 128.5 (C- ar); 128.3 (C-ar); 127.2 (C-ar); 1 12.0 (C-furil); 1 10.0 (C-furil); 57.6 (O-CH₂-furil). HPLC: pureza 98 %. EM (ES): m/ z = 225, 227. Análisis elemental para CnH₈CI₂O₂: hallado %C 54.06, % H 3.33, %CI 29.08, teórico %C 54.35 %H 3.32 %CI 29.17. Síntesis de los derivados de 3,4,5-trietoxibenzoato-5-fenil-2-furilmetilo

On a suspension of LiAIH ₄ (66 mg, 1.75 mmol) in THF (10 ml), 5- (2,4-dichlorophenyl) -2 furoic acid (300 mg, 1,16 mmol) dissolved in THF is added (5 mi) at 0 ° C. It is kept under stirring and at room temperature for 15 minutes. Finally, the reaction mixture is added water (2 ml) slowly at 0 ° C and filtered through Celite. The reaction mixture is extracted with acetate / water (30 ml). Yield: yellow solid (72 mg, 61%). ¹ H-NMR (CDCI ₃ , 300 MHz) δ: 7.81 (d, J = 8.79 Hz, 1 H, H-ar); 7.45 (d, J = 2.20 Hz, 1 H, H-ar); 7.30 (d, J = 8.79 Hz, 1 H, H-ar); 7.07 (d, J = 3.07 Hz, 1 H, H-furil); 6.43 (d, J = 3.51 Hz, 1 H, H-furil); 4.68 (s, 2H, O-Chb-furil). ¹³ C-NMR (CDCI _3, 75 MHz) δ: 153.8 (C-furyl); 149.3 (C-furil); 133.1 (C-ar); 130.6 (C-ar); 130.4 (C-ar); 128.5 (C-ar); 128.3 (C-ar); 127.2 (C-ar); 1 12.0 (C-furil); 1 10.0 (C-furil); 57.6 (O-CH ₂ -furyl). HPLC: 98% purity. MS (ES): m / z = 225, 227. Elemental analysis for CnH ₈ CI ₂ O ₂ : found% C 54.06,% H 3.33,% CI 29.08, theoretical% C 54.35% H 3.32% CI 29.17. Synthesis of 3,4,5-triethoxybenzoate-5-phenyl-2-furylmethyl derivatives

 General method

 On a solution of 3,4,5-triethoxybenzoic acid or 3,4,5-trimethoxybenzoic acid (1, 2 equivalents) in 10 ml of dichloromethane, the coupling agent (1, 2 equivalents) is added and stirred for 1 hour. Then, the corresponding 5-phenyl-2-furyl methanol derivative (1 equivalent), TEA (2 equivalents) is added as a base and stirred at room temperature for the time indicated in each case. Finally, the solvent is removed by evaporating under reduced pressure. The obtained residue is purified by silica gel column chromatography using the eluents indicated in each case.

5- (4-Nitrophenyl) -2-furylmethyl 3,4,5-triethoxybenzoate (MR 1.44): Obtained according to the general methodology described above. Reagents: 3,4,5-triethoxybenzoic acid (100 mg, 0.39 mmol), DCC (132 mg, 0.43 mmol), 5- (4- nitrophenyl-2-furyl methanol (94 mg, 0.43 mmol) Reaction time: 24 hours Purification: eluent hexane / ethyl acetate (6: 1) Yield: solid yellow (60 mg, 16%). Mp = 1 18.8 ° C. H ¹ - NMR (CDCI ₃ , 300 MHz) δ: 8.23 (d, J = 9.0 Hz, 2H, H-ar); 7.78 (d, J = 9.0 Hz, 2H, H-ar); 7.23 (s, 2H, H-ar); 6.84 (d, J = 3.4 Hz, 1 H, H-fury); 6.61 (d, J = 3.4 Hz, 1 H, H-fury); 5.33 (s, 2H, O-Chb-fury); 4.13-4.04 (m, 6H, O-CH2CH3); 1.38 (t, J = 6.9 Hz, 6H, O-CH ₂ CH ₃ ); 1.32 (t, J = 7.1 Hz, 3H, O-CH ₂ CH ₃ ). ¹³ C-NMR (CDCI3, 75 MHz) δ 166.3 (CO); 153.1 (C-ar); 152.5 (C-ar); 151.9 (C-furil); 147.1 (C-ar); 136.5 (C-ar); 130.2 (C-ar); 124.7 (C-ar); 124.5 (C-ar); 1 13.8 (C-furil); 1 10.2 (C-furil); 109.1 (C-ar); 69.4 (O-CH ₂ CH ₃ ); 65.3 (O-CH ₂ CH ₃ ); 58.8 (0-CH ₂ -furyl); 15.9 (O-CH ₂ CH ₃ ); 15.2 (0-CH ₂ CH ₃ ). HPLC: purity> 99%. MS (ES): m / z = 456 (M + H) ⁺ . Elemental analysis for C ₂ 4H ₂₅ N0 ₈ : theoretical% C 63.29% H 5.53% N 3.08, found% C 63.10% H 5.34% N 3.28.

5- (4-Methylphenyl) -2-furylmethyl 3,4,5-triethoxybenzoate (MR 1.61): Obtained according to the general methodology described above. Reagents: 3,4,5-triethoxybenzoic acid (170 mg, 0.67 mmol), PyBOP (331 mg, 0.64 mmol), 5- (4- methylphenyl) -2-furyl methanol (100 mg, 0.53 mmol), TEA (147 μΙ , 1.06 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (8: 1). Yield: yellow solid (162 mg, 57%). Mp = 75.6 ° C. ¹ H-NMR (300 MHz, CDCI ₃ ) δ 7.58 (d, J = 8.3 Hz, 2H, H-ar); 7.28 (s, 2H, H-ar); 7.19 (d, J = 8.5 Hz, 2H, H-ar); 6.54 (d, J = 3.3 Hz, 1 H, H-fury); 6.56 (d, J = 3.3 Hz, 1 H, H-fury); 5.32 (s, 2H; O-Chb-furyl); 4.09 (m, 6H, O-ChbCHs), 2.36 (s, 3H, CH ₃ ); 1.42 (t, J = 6.9 Hz, 6H, 0-CH ₂ CH ₃ ); 1.35 (t, J = 7.9 Hz, 3H, 0-CH ₂ CH ₃ ). ¹³ C-NMR (75 MHz, CDCI ₃ ) δ 166.5 (CO); 155.2 (C-furil); 153.0 (3C, C-ar); 149.1 (C-furil); 137.9 (C-ar); 130.1 (C-ar); 129.7 (2C, C-ar); 125.0 (C-ar); 1 13.6 (C-ar); 109.1 (C-furil); 105.6 (C-furil); 69.42 (O-CH ₂ CH ₃ ); 65.21 (2C, O-CH ₂ CH ₃ ); 59.2 (O-CH ₂ -furyl), 31 .3 (CH ₃ ), 15.9 (O-CH ₂ CH ₃ ); 15.3 (2C, O-CH ₂ CH ₃ ). HPLC purity> 99%. MS (ES): m / z = 181. Elemental analysis for C ₂₅ H ₂₈ O ₆ : theoretical% C 70.74% H 6.65; found% C 70.45% H 6.38. 5-phenyl-2-furylmethyl 3,4,5-triethoxybenzoate (MR 1.62): Obtained according to the general methodology described above. Reagents: 3,4,5-triethoxybenzoic acid (175 mg, 0.68 mmol), PyBOP (358 mg, 0.68 mmol), 5-phenyl-2- Furyl methanol (100 mg, 0.57 mmol), TEA (158 μΙ, 1.15 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (8: 1). Yield: yellow solid (246 mg, 87%). P. f = 71 .1 ° C. ¹ H-NMR (300 MHz, CDCI ₃ ) δ 7.70-7.29 (m, 7H, H-ar); 6.64 (d, J = 3.3 Hz, 1 H, H-fury); 6.56 (d, J = 3.3 Hz, 1 H, H-fury); 5.33 (s, 2H; O-ChU-furil); 4.10 (m, 6H, O-CH2CH3); 1.42 (t, J = 6.7 Hz, 6H, O-CH2CH3); 1.35 (t, J = 7.0 Hz, 3H, O-CH ₂ CH ₃ ). ¹³ C-NMR (75 Mhz, CDCI3) δ 166.5 (CO); 153.0 (C-furil); 149.5 (3C, C-ar); 149.1 (C-furil); 129.2 (C-ar); 125.7 (C-ar); 128.1 (2C, C-ar); 125.7 (C-ar); 124.3 (C-ar); 124.4 (C-ar); 1 13.7 (2C, C-ar); 108.8 (C-furil); 106.3 (C-furil); 69.4 (O-CH ₂ CH ₃ ); 65.2 (2C, O-CH ₂ CH ₃ ); 59.2 (0-CH ₂ -furyl); 16.0 (O-CH ₂ CH ₃ ); 15.2 (0-CH ₂ CH ₃ ). HPLC: purity> 99%. MS (ES): m / z = 449 (M + K) ⁺ . Elemental analysis for C ₂₅ H ₂ 80 ₅ : theoretical% C 70.23% H 6.38; found% C 70.51% H 6.19.

3,4,5-Trimethoxybenzoate 5- (4-nitrophenyl) -2-furylmethyl (MR 2.50): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzoic acid (500 mg, 2.33 mmol), PyBOP (1,213 g, 2.33 mmol), 5- (4-nitrophenyl) -2-furyl methanol (438 mg, 1 .94 mmol), TEA (536 μΙ, 3.88 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (3: 1). Yield: white solid (57 mg, 7%). Mp = 137.1 ° C. ¹ H-NMR (300 MHz, CDCI ₃ ) δ 8.18 (d, J = 8.8 Hz, 2H, H-ar); 7.75 (d, J = 9.0 Hz, 2H, H-ar); 7.19 (s, 2H, H-ar); 6.80 (d, J = 3.4 Hz, 1 H, H-fury); 6.58 (d, J = 3.4 Hz, 1 H, H-fury); 5.31 (s, 2H, 0-CH ₂ -furyl); 3.83 (s, 9H; OCH ₃ ). ¹³ C-NMR (75 MHz, CDCI ₃ ) δ 166.2 (CO); 153.4 (2C, C-ar); 152.6 (C-furil); 151.7 (C-furil); 147.0 (C-ar); 142.9 (C-ar); 136.4 (C-ar); 125.0 (2C, C-ar); 124.7 (C-ar); 124.5 (2C, C-ar); 1 13.9 (C-furil); 1 10.2 (C-furil); 107.4 (2C, C-ar); 61 .3 (OCH ₃ ); 58.9 (O-CH ₂ -furyl); 56.7 (2C, OCH ₃ ). HPLC: purity = 93%. MS (ES): m / z = 371. Elemental analysis for C ₂ and Hi ₉ NO ₈ : theoretical% C 61 .02% H 4.63% N 3.39; Found% C 60.78% H 4.54% N 3.29. 5- (2,4-Dichlorophenyl) -2-furylmethyl 3,4,5-trimethoxybenzoate (MR 2.51): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzoic acid (99 mg, 0.46 mmol), PyBOP (241 mg, 0.46 mmol), 5- (2, 4-dichlorophenyl) -2-furyl methanol (100 mg, 0.39 mmol), TEA (536 μΙ, 3.88 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (6: 1). Yield: white solid (23 mg, 14%). P. f = 120.4 ° C. ¹ H-NMR (300 MHz, CDCI ₃ ) δ 7.82 (d, J = 8.6 Hz, 1 H, H-ar); 7.46 (d, J = 2.1 Hz, 1 H, H-ar); 7.32 (s, 2H, H-ar); 7.28 (d, J = 2.1 Hz, 1 H, H-ar); 7.1 1 (d, J = 3.4 Hz, 1 H, H-furil); 6.62 (d, J = 3.4 Hz, 1 H, H-fury); 5.36 (s, 2H, O-Chb-furil); 3.90 (s, 9H, OCH3). ¹³ C-NMR (75 MHz, CDCI ₃ ) δ 166.3 (CO); 153.4 (2C, C-ar); 150.3 (C-furil); 149.8 (C-ar); 142.8 (C-furil); 133.8 (C-furil); 131 .1 (C-ar); 130.9 (C-ar); 129.1 (C-ar); 127.9 (C-ar); 127.7 (C-ar); 125.1 (C-ar); 1 13.5 (C-furil); 1 12.5 (C-furil); 107.4 (2C, C-ar); 59.0 (O-CH ₂ -furyl); 61 .3 (OCH ₃ ). HPLC: purity = 96%. MS (ES): m / z = 438 (M + H) ⁺ . Elemental analysis for C ₂ and Hi ₈ CI ₂ 0 ₆ : theoretical% C 57.68% H 4.15% C \ 16.22; found% C 57.72% H 4.18% C \ 16.34.

Synthesis of the 5,5-phenyl-2-furoate derivatives of 3,4,5-trimethoxybenzyl or 3,4,5-triethoxybenzyl

General method

 On a solution of the corresponding 5-phenyl-2-furoic acid derivative (1.2 equivalents) in 10 ml of dichloromethane, add the PyBOP coupling agent (1.2 equivalent) and stir at room temperature for one hour. Then, 3,4,5-trimethoxybenzyl or 3,4,5-triethoxybenzyl alcohol (1 equivalent) and TEA (2 equivalents) are added as a base and stirred at room temperature for the time indicated in each case. Finally, the solvent is removed by evaporating under reduced pressure. The residue obtained is purified by silica gel column chromatography using the eluents indicated in each case.

5-(2,4-diclorofenil)-2-furoato de 3,4,5-trimetoxibencilo (MR 1.48): Se obtiene según la metodología general descrita anteriormente. Reactivos: alcohol 3,4,5-trimetoxibencílico (159 μΙ, 0.93 mmol), ácido 5-(2,4-diclorofenil)-2- furoico (200 mg, 0.78 mmol), PyBOP (485 mg, 0.93 mmol), TEA (215 μΙ, 1 .55 mmol). Tiempo de reacción: 24 horas. Purificación: eluyente hexano/ acetato de etilo (6: 1 ). Rendimiento: sólido amarillo (225 mg, 55 %). P.f = 125.4 °C. ¹ H- RMN (300 MHz, CDCI₃) δ: 7.91 (d, J = 8.6 Hz, 1 H, H-ar); 7.46 (d, J = 2.0 Hz, 1 H, H-ar); 7.31 (dd, J = 8.6 y 2.1 Hz, 1 H, H-ar); 7.28 (d, J = 3.7 Hz, 1 H, H-furil); 7.18 (d, J = 3.7 Hz, 1 H, H-furil); 6.66 (s, 2H, H-ar); 5.57 (s, 2H, O-CH₂-ar); 3.87 (s, 6H, OCH₃); 3.62 (s, 3H, OCH₃). ¹³C-RMN (75MHz, CDCI₃), δ: 158.8 (CO); 153.8 (C-furil); 153.3 (C-furil); 143.9 (C-furil); 132.0 (C-ar); 135.2 (C-ar); 131 .0 (C-ar); 130.0 (C-ar); 127.9 (C-ar); 120.3 (C-furil); 1 13.1 (C-furil); 106.2 (C-ar); 67.3 (O-CH₂-ar); 61 .6 (2C, OCH₃); 56.6 (OCH₃). HPLC: pureza = 96 %. EM (ES): m/ z = 459 (M+Na)⁺. Análisis elemental para C₂i Hi₈CI₂O₆: teórico %C 57.68 %H 4.15 %CI 16.22; hallado %C 57.39 %H 4.31 %CI 16.26.

3,4,5-Trimethoxybenzyl 5- (2,4-dichlorophenyl) -2-furoate (MR 1.48): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzyl alcohol (159 μΙ, 0.93 mmol), 5- (2,4-dichlorophenyl) -2-furoic acid (200 mg, 0.78 mmol), PyBOP (485 mg, 0.93 mmol), TEA (215 μΙ, 1.55 mmol). Reaction time: 24 hours. Purification: eluent hexane / ethyl acetate (6: 1). Yield: yellow solid (225 mg, 55%). Mp = 125.4 ° C. ¹ H-NMR (300 MHz, CDCI ₃ ) δ: 7.91 (d, J = 8.6 Hz, 1 H, H-ar); 7.46 (d, J = 2.0 Hz, 1 H, H-ar); 7.31 (dd, J = 8.6 and 2.1 Hz, 1 H, H-ar); 7.28 (d, J = 3.7 Hz, 1 H, H-fury); 7.18 (d, J = 3.7 Hz, 1 H, H-furil); 6.66 (s, 2H, H-ar); 5.57 (s, 2H, O-CH ₂ -ar); 3.87 (s, 6H, OCH ₃ ); 3.62 (s, 3H, OCH ₃ ). ¹³ C-NMR (75MHz, CDCI ₃ ), δ: 158.8 (CO); 153.8 (C-furil); 153.3 (C-furil); 143.9 (C-furil); 132.0 (C-ar); 135.2 (C-ar); 131.0 (C-ar); 130.0 (C-ar); 127.9 (C-ar); 120.3 (C-furil); 1 13.1 (C-furil); 106.2 (C-ar); 67.3 (O-CH ₂ -ar); 61.6 (2C, OCH ₃ ); 56.6 (OCH ₃ ). HPLC: purity = 96%. MS (ES): m / z = 459 (M + Na) ⁺ . Elemental analysis for C ₂ and Hi ₈ CI ₂ O ₆ : theoretical% C 57.68% H 4.15% CI 16.22; found% C 57.39% H 4.31% CI 16.26.

3,4,5-Trimethoxybenzyl 5- (4-methylphenyl) -2-furoate (MR 1.50): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzyl alcohol (196 μΙ, 1,115 mmol), 5- (4-methylphenyl) -2-furoic acid (200 mg, 0.96 mmol), PyBOP (599 mg, 1,115 mmol) , TEA (265 μΙ, 1.92 mmol). Reaction time: 22 hours. Purification: eluent hexane / ethyl acetate (6: 1). Yield: white solid (121 mg, 33%). Mp = 144.6 ° C. ¹ H-NMR (300 MHz, CDCI ₃ ) δ 7.67 (d, J = 8.2 Hz, 2H, H-ar); 7.29-7.21 (m, 4H, H-ar, H-fury); 6.69 (s, 2H, H-ar); 5.50 (s, 2H, O-Chb-ar); 3.92-3.85 (m, 9H, OCH ₃ ); 2.35 (s, 3H, CH ₃ ). ¹³ C-NMR (75 MHz, CDCI ₃ ) δ 159.0 (CO); 158.5 (C-furil); 153.7 (2C, C-ar); 143.5 (C-furil); 139.6 (C-ar); 139.0 (C-ar); 131.8 (C-ar); 129.9 (2C, C-ar); 127.2 (C-ar); 125.5 (2C, C-ar); 120.8 (C-furil); 106.6 (C-furil); 106.0 (2C, C-ar); 67.0 (O-CH ₂ -ar); 61 .2 (OCH ₃ ); 56.5 (2C, OCH ₃ ); 21 .8 (CH ₃ ). HPLC: purity> 99%. MS (ES): m / z = 405 (M + Na) ⁺ . Elemental analysis for C ₂₂ H ₂₂ 0 ₆ : theoretical% C 69.10% H 5.80 found% C 68.89% H 9.18.

3,4,5-Trimethoxybenzyl 5-phenyl-2-furoate (MR 1.51): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzyl alcohol (210 μΙ, 1 .27 mmol), 5-phenyl-2-furoic acid (200 mg, 1.03 mmol), PyBOP (639 mg, 1 .23 mmol), TEA (284 μΙ, 2.06 mmol). Reaction time: 23 hours. Purification: eluent hexane / ethyl acetate (8: 1). Yield: white solid (90 mg, 24%). Mp = 98.4 ° C. ¹ H-NMR (300 MHz, CDCI3) δ 7.79 (d, J = 6.9 Hz, 2H, H-ar); 7.45-7.26 (m, 5H, H-ar, H-fury); 6.69 (s, 2H, H-ar); 5.29 (s, 2H, O-Chb-ar); 3.93-3.85 (m, 9H, OCH ₃ ). ¹³ C-NMR (75 MHz, CDCI3) δ 159.0 (CO); 158.2 (C-furil); 153.7 (2C, C-ar); 143.9 (C-furil); 138.5 (C-ar); 131.7 (C-ar); 129.8 (C-ar); 129.4 (C-ar); 129.2 (2C, C-ar); 125.3 (2C, C-ar); 120.7 (C-furil); 107.3 (C-furil); 106.1 (2C, C-ar); 67.1 (O-CH ₂ -ar); 61 .2 (OCH ₃ ); 56.6 (2C, OCH3). HPLC: purity = 97%. MS (ES): m / z = 391 (M + Na) ⁺ . Elemental analysis for C ₂ and H ₂₀ O ₆ : theoretical% C 68.47% H 5.47 found% C 68.09% H 5.71.

3,4,5-Trimethoxybenzyl 5- (4-nitrophenyl) -2-furoate (MR 1.52): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzyl alcohol (168 μΙ, 0.98 mmol), 5- (4-nitrophenyl) -2-furoic acid (200 mg, 0.82 mmol), PyBOP (509 mg, 0.98 mmol), TEA (227 μΙ, 1.64 mmol). Reaction time: 24 hours. Purification: eluent hexane / ethyl acetate (4: 1). Yield: white solid (34 mg, 10%). Mp = 161 .2 ° C. ¹ H-NMR (300 MHz, CDCI3) δ 7.52 (d, J = 9.0 Hz, 2H, H-ar); 7.93 (d, J = 9.0 Hz, 2H, H-ar), 7.31 (d, J = 3.6 Hz, 1 H; H-furil); 6.95 (d, J = 3.6 Hz, 1 H, H-fury); 6.69 (s, 2H, H-ar); 5.30 (s, 2H, O-Chb-ar); 3.93-3.86 (m, 9H, OCH ₃ ). ¹³ C-NMR (75 MHZ, CDCI ₃ ) δ 158.6 (CO); 155.4 (C-furil); 153.8 (2C, C-ar); 147.9 (C-furil); 145.6 (C-ar); 143.2 (C-ar); 135.4 (C-ar); 131.4 (C-ar); 125.7 (2C, C-ar); 124.8 (2C, C-ar); 120.6 (C-furil); 1 10.5 (C-furil); 106.3 (2C, C-ar); 67.5 (O-CH ₂ -ar); 61 .3 (OCH ₃ ); 56.6 (2C, OCH ₃ ). HPLC: purity> 99%. MS (ES): m / z = 436 (M + Na) ⁺ . Elemental analysis for C ₂ and Hi ₉ N0 ₈ : theoretical% C 61 .02% H 4.63% N 3.39 found% C 60.97% H 4.75% N 3.65. 5- (2-Nitro-4-chlorophenyl) -2,4,5-trimethoxybenzyl furoate (MR 2.20): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzyl alcohol (101 μΙ, 0.61 mmol), 5- (2-nitro-4- chlorophenyl) -2-furoic acid (200 mg, 0.71 mmol), PyBOP (369 mg, 0.71 mmol) , TEA (164 μΙ, 1.19 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (6: 1). Yield: white solid (130 mg, 38%). Mp = 147.3 ° C. ¹ H-NMR (CDCI ₃ , 300 MHz) δ 8.37-7.87 (m, 5H, H-ar); 7.86 (d, J = 3.6 Hz, 1 H, H-fury); 7.30 (d, J = 3.6 Hz, 1 H, H-furil); 5.87 (s, 2H, O-CJi-ar); 4.48 (s, 6H, OCH3); 4.44 (s, 3H, OCH ₃ ). ¹³ C-NMR (CDCI _3, 75 MHz) δ 158.5 (CO); 153.8 (2C, C-ar); 151 .1 (C-furil); 148.4 (C-ar); 145.6 (C-furil); 138.5 (C-ar); 136.1 (C-ar); 132.8 (C-ar); 131.4 (C-ar); 131 .2 (C-ar); 124.9 (C-ar); 122.0 (C-ar); 124.8 (C-ar); 120.2 (C-furil); 1 12.2 (C-furil); 106.0 (2C, C-ar); 67.44 (2C, O-CH ₂ -ar); 61 .3 (OCH3); 56.6 (2C, OCH ₃ ). HPLC purity> 99%. MS (ES): m / z = 470 (M + Na) ⁺ . Elemental analysis for C ₂₅ H ₂₈ O ₅ : theoretical% C 56.32% H 4.05% N 3.18; found% C 56.07% H 4.02% N 2.99.

3,4,5-Trimethoxybenzyl 5- (2-trifluoromethylphenyl) -2-furoate (MR 2.21): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzyl alcohol (129 μΙ, 0.65 mmol), 5- (2- trifluoromethylphenyl) -2-furoic acid (200 mg, 0.76 mmol), PyBOP (393 mg, 0.76 mmol), TEA (174 μΙ, 1.26 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (6: 1). Yield: white solid (123 mg, 36%). P. f = 89.8 ° C. ¹ H-NMR (CDCI ₃ , 300 MHz) δ 7.80 (dd, 2H, J = 10.8 and 8.0 Hz, H-ar); 7.68 (t, J = 7.4 Hz, 1 H, H-ar); 7.53 (t, J = 7.8 Hz, 1 H, H-ar); 7.30 (d, J = 4.0 Hz, 1 H, H-furil); 6.79 (d, J = 3.5 Hz, 1 H, H-furil); 6.69 (s, 2H, H-ar); 5.30 (s, 2H, O-Chb-ar), 3.89 (s, 6H, OCH ₃ ); 3.86 (s, 3H, OCH ₃ ). ¹³ C NMR (CDCI _3, 75 MHz) δ 158.8 (CO); 154.5 (C-furil); 153.7 (2C, C-ar); 144.8 (C-furil); 138.5 (C-ar); 132.3 (C-ar); 131.6 (C-ar); 131 .1 (C-ar); 129.5 (C-ar); 128.8 (C-ar); 127.3 (c, J = 17.3 and 5.7 Hz, C-CF _3, ) 124.1 (d, J = 273.4 Hz, CF ₃ ); 120.2 (C-furil); 1 12.4 (C-furil); 106.1 (2C, C-ar); 67.2 (O-CH ₂ -ar); 61 .3 (OCH ₃ ); 56.5 (2C, OCH ₃ ). HPLC purity = 94%. MS (ES): m / z = 459 (M + Na) ⁺ . Elemental analysis for C ₂₂ Hi ₉ F ₃ 0 ₆ : theoretical% C 60.55% H 4.39, found% C 60.37% H 4.31.

5- (2-Nitro-4-methylphenyl) -2,4,5-trimethoxybenzyl furoate (MR 2.24): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzyl alcohol (1 12 μΙ, 0.66 mmol), 5- (2-nitro-4- methylphenyl) -2-furoic acid (200 mg, 0.79 mmol), PyBOP (412 mg, 0.79 mmol ), TEA (182 μΙ, 1.32 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (3: 1). Yield: white solid (27 mg, 10%). Mp = 148.3 ° C. ¹ H-NMR (CDCI ₃ , 300 MHz): δ: 7.67 (d, 1 H, J = 7.8 Hz, H-ar); 7.60 (s, 1 H, H-ar); 7.43 (d, 1 H, J = 7.9 Hz, H-ar); 7.28 (s, 1 H, H-fury); 6.66 (m, 3H, H-ar, H-furyl); 5.27 (s, 2H, O-Chb-Ar); 3.89 (s, 6H, OCH ₃ ); 3.85 (s, 3H, OCH ₃ ); 2.47 (s, 3H, CH ₃ ). ¹³ C NMR (CDCI _3, 75 MHz) δ 158.6 (CO); 153.8 (2C, C-ar); 152.6 (C-ar); 148.3 (C-furil); 145.0 (C-furil); 141 .2 (C-ar); 138.5 (C-ar); 133.3 (C-ar); 131.5 (C-ar); 130.1 (C-ar); 124.9 (C-ar); 120.9 (C-ar); 120.2 (C-furil); 1 1 1 .3 (C-furil); 106.0 (2C, C-ar); 67.2 (O-CH ₂ -ar); 61 .2 (OCH ₃ ); 56.6 (2C, OCH ₃ ); 21.5 (CH ₃ ). HPLC purity = 90%. MS (ES): m / z = 450 (M + Na ⁺ ) ⁺ . Elemental analysis for C ₂₂ H ₂ iNO ₈ : theoretical% C 61 .82% H 4.95% N 3.28, found% C 61 .81% H 4.82% N 3.44.

3,4,5-Trimethoxybenzyl 5- (3-trifluoromethylphenyl) -2-furoate (MR 2.30): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzyl alcohol (105 μΙ, 0.62 mmol), 5- (3- trifluoromethylphenyl) -2-furoic acid (200 mg, 0.74 mmol), PyBOP (405 mg, 0.78 mmol), TEA (171 μΙ, 1.24 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (6: 1). Yield: white solid (235 mg, 87%). Mp = 107.7 ° C. ¹ H-NMR (CDCI ₃ , 300 MHz) δ 8.02 (s, 1 H, H-ar); 7.96 (d, J = 6.8 Hz, 1 H, H-ar); 7.62-7.53 (m, 2H, H-ar); 7.30 (d, J = 3.6 Hz, 1 H, H-furil); 6.85 (d, J = 3.6 Hz, 1 H, H-fury); 6.71 (s, 2H, H-ar); 5.31 (s, 2H, O-CJi-ar); 3.90 (s, 6 H, OCH ₃ ); 3.86 (s, 3H, OCH3). ¹³ C-NMR (CDCI3, 75 MHz) δ 158.8 (CO); 156.4 (C-furil); 153.9 (2C, C-ar); 144.6 (C-furil); 138.5 (C-ar); 132.2 (C-ar); 131.5 (c, J = 32.7 Hz, C-CF ₃ ); 130.6 (C-ar); 130.0 (C-ar); 125.8 (c, J = 2.9 Hz, C-ar); 123.9 (d, J = 272.5 Hz, CF ₃ ); 122.0 (c, J = 2.9 Hz, C-ar); 120.6 (C-furil); 108.5 (C-furil); 106.1 (2C, C-ar); 67.30 (O-CH ₂ -ar); 61 .2 (OCH ₃ ), 56.6 (2C, OCH ₃ ). HPLC: purity> 99%. MS (ES): m / z = 181. Elemental analysis for C ₂₂ H 19 F ₃ 0 ₆ : theoretical:% C 60.55,% H 4.39, found% C 60.34,% H 4.31.

3,4,5-Trimethoxybenzyl 5- (4-methoxyphenyl) -2-furoate (MR 2.31): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzyl alcohol (126 μΙ, 0.74 mmol), 5- (4-methoxyphenyl) -2-furoic acid (200 mg, 0.89 mmol), PyBOP (462 mg, 0.89 mmol), TEA (205 μΙ, 1.48 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (3: 1). Yield: white solid (205 mg, 70%). Mp = 137.0 ° C. ¹ H-NMR (CDCI3, 300 MHz) δ 8.29 (d, J = 8.6 Hz, 2H, H-ar); 7.83 (s, 2H, H-ar); 7.52 (d, J = 8.7 Hz, 2H, H-ar); 7.18 (d, J = 3.5 Hz, 1 H; H-fury); 5.85 (s, 2H, 0-CH ₂ -ar); 4.46 (s, 6H, OCH3); 4.43 (s, 6H, H-1, OCH ₃ ). ¹³ C NMR (CDCI _3, 75 MHz) δ 160.7 (CO); 159.1 (C-ar); 158.4 (C-furil); 153.7 (2C, C-ar); 143.3 (C-ar); 131.9 (C-ar); 126.9 (C-ar); 122.8 (C-ar); 122.0 (C-furil); 1 14.7 (2C, C-ar); 106.0 (2C, C-ar); 105.8 (C-furil); 66.9 (O-CH ₂ -ar); 61 .3 (OCH ₃ ); 56.6 (OCH ₃ ); 55.8 (OCH ₃ ). MS (ES): m / z = 421 (M + Na ⁺ ). HPLC: purity = 97%. Elemental analysis for C ₂₂ H ₂₂ O ₇ : theoretical:% C 66.32,% H 5.57, Found% C 66.03% H 5.57.

3,4,5-Trimethoxybenzyl 5- (2-chloro-5-trifluoromethylphenyl) -2-furoate (MR 2.32): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzyl alcohol (141 μΙ, 0.83 mmol), 5- (2-chloro-5-trifluoromethylphenyl) -2-furoic acid (200 mg, 0.99 mmol), PyBOP (516 mg, 0.99 mmol) , TEA (228 μΙ, 1.65 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (6: 1). Yield: white solid (100 mg, 26%). Mp = 129.1 ° C. ¹ H-NMR (300 MHz, CDCI ₃ ) δ 8.23 (s, 1 H, H-ar); 7.59 (d, J = 8.4 Hz, 1 H, H-ar); 7.52 (d, J = 10.5 Hz, 1 H, H-ar); 7.32 (d, J = 3.7 Hz, 1 H, H-furil); 7.28 (d, J = 3.7 Hz, 1 H, H-fury); 6.70 (s, 2H, H-ar); 5.32 (s, 2H, O-CH ₂ -ar); 3.89 (s, 6H, OCH ₃ ); 3.85 (s, 3H, OCH ₃ ). ¹³ C-NMR (75 MHz, CDCI ₃ ) δ 158.7 (CO); 153.8 (2C, C-ar); 152.6 (C-ar); 144.5 (C-furil); 138.5 (C-furil); 134.9 (C-ar); 131.9 (C-ar); 131.5 (C-ar); 126.2 (c, J = 13.5 Hz, C-CF ₃ ); 125.7 (d, J = 272.5 Hz, CF3); 122.0 (C-ar); 120.3 (C-furil); 1 14.1 (C-furil); 106.0 (2C, C-ar); 67.4 (0-CH ₂ -ar); 61 .3 (OCH ₃ ); 56.6 (2C, OCH ₃ ). HPLC purity = 94%. MS (ES): m / z = 181. Elemental analysis for C ₂₂ Hi ₈ CIF ₃ 0 ₆ : theoretical% C 56.12% H 3.85, found% C 55.92% H 3.87.

3,4,5-Triethoxybenzyl 5- (4-methylphenyl) -2-furoate (MR 1.57): Obtained according to the general methodology described above. Reagents: 3,4,5-triethoxybenzyl alcohol (197 μΙ, 0.79 mmol), 5- (4-methylphenyl) -2-furoic acid (200 mg, 0.96 mmol), PyBOP (623 mg, 1 .20 mmol), TEA (221 μΙ, 1.60 mmol). Reaction time: 18 hours. Purification: eluent hexane / ethyl acetate (8: 1). Yield: white solid (77 mg, 10%). Mp = 99.7 ° C. ¹ H-NMR (300 MHz, CDCI ₃ ) δ 7.67 (d, J = 8.2 Hz, 2H, H-ar); 7.22 (d, J = 8.3 Hz, 2H, H-fury); 6.69 (d, J = 3.6 Hz, 2H, H-fury); 6.66 (s, 2H, H-ar); 5.25 (s, 2H, O-CI ^ -ar); 4.06-4.13 (m, 6H, O-CH ₂ CH ₃ ); 2.38 (s, 3H, Me); 1.43 (t, 6H, J = 7.0 Hz, O-CH ₂ CH ₃ ); 1.36 (t, 3H, J = 7.1 Hz, O-CH ₂ CH ₃ ). ¹³ C-NMR (75 MHz, CDCI ₃ ) δ 159.1 (CO); 152.5 (C-12); 153.4 (2C, C-ar); 143.6 (C-furil); 139.5 (C-ar); 138.4 (C-ar); 131.3 (C-ar); 129.9 (C-ar); 125 (C-ar); 120.8 (C-furil); 107.6 (2C, C-ar); 106.6 (C-furil); 69.2 (O-CH _2- -ar); 67.0 (O-CH ₂ -CH ₃ ); 65.1 (O-CH ₂ -CH ₃ ); 21 .8 (Me); 16.0 (O-CH ₂ - CH ₃ ); 15.3 (2C, -OCH ₂ -CH ₃ ). HPLC: purity> 99%. MS (ES): m / z = 447 (M + Na) ⁺ . Elemental analysis for C ₂₅ H ₂₈ O ₆ : theoretical% C 70.44% H 6.65; found% C 70.25% H 6.58. 3,4,5-Triethoxybenzyl 5-phenyl-2-furoate (MR 1.58): Obtained according to the general methodology described above. Reagents: 3,4,5-triethoxybenzyl alcohol (314 μΙ, 1.28 mmol), 5-phenyl-2-furoic acid (300 mg, 1.55 mmol), PyBOP (998 mg, 1.92 mmol), TEA (354 μΙ, 2.56 mmol). Reaction time: 18 hours. Purification: eluent hexane / ethyl acetate (8: 1). Yield: white solid (196 mg, 38%). Mp = 88.8 ° C. ¹ H-NMR (300 MHz, CDCI ₃ ) δ 7.76 (d, J = 7.0 Hz, 2H, H-ar); 7.37 (m, 4H, H-ar, H-fury); 6.72 (d, J = 8.6 Hz, 1 H, H-furil); 6.64 (s, 2H, H-ar); 5.26 (s, 2H, O-CH ₂ -ar); 4.07 (m, 6H, O-ChbCHs); 1.41 (t, J = 7.0, 6H, O-CH ₂ CH ₃ ); 1.53 (t, J = 7.1 Hz, 3H, O-CH ₂ CH ₃ ). ¹³ C-NMR (75 MHz, CDCI ₃ ) δ 159.0 (CO); 158.1 (C-furil); 153.4 (2C, C-ar); 143.9 (C-ar); 138.5 (C-ar); 131.3 (C-ar); 129.9 (C-furil); 129.4 (C-ar); 129.2 (2C, C-ar); 125.3 (2C, C-ar); 120.7 (C-furil); 107.7 (2C, C-ar); 107.3 (C-furil); 69.3 (O-CH ₂ - CH ₃ ); 67.1 (O-CH ₂ -ar); 65.1 (O-CH ₂ -CH ₃ ); 16.0 (O-CH ₂ -CH ₃ ); 15.3 (2C, O-CH ₂ - CH ₃ ). HPLC: purity = 98%. MS (ES): m / z = 433 (M + Na) ⁺ . Elemental analysis for C ₂ 4H ₂₆ O ₆ : theoretical% C 70.23% H 6.38; found% C 70.15% H 6.09.

3,4,5-Triethoxybenzyl 5- (4-nitrophenyl) -2-furoate (MR 1.59): Obtained according to the general methodology described above. Reagents: 3,4,5-triethoxybenzyl alcohol (171 μΙ, 0.69 mmol), 5- (4-nitrophenyl) -2-furoic acid (200 mg, 0.82 mmol), PyBOP (530 mg, 1.02 mmol), TEA (189 μΙ, 1.37 mmol). Reaction time: 24 hours. Purification: eluent hexane / ethyl acetate (6: 1). Yield: pale yellow solid (10 mg, 35%). Mp = 107.8 ° C. ¹ H-NMR (300 MHz, CDCI ₃ ) δ 8.30 (d, J = 8.9 Hz, 2H, H-ar); 7.94 (d, J = 9.0 Hz, 2H, H-ar); 7.32 (d, J = 3.6 Hz, 1 H, H-fury); 6.95 (d, J = 3.5 Hz, 1 H, H-furil); 6.67 (s, 2H, H-ar), 5.42 (s, 2H, O-CJi-ar); 4.12 (m, 6H, O-CJiCHs); 1.41 (m, 9H, O-CH ₂ CH ₃ ). ^13- C-NMR (75 MHz, CDCI ₃ ) δ 158.7 (CO); 155.3 (C-furil); 153.5 (2C, C-ar); 147.9 (C-ar); 145.7 (C-furil); 138.7 (C-ar); 135.4 (C-ar); 130.8 (C-ar); 125.7 (2C, C-ar); 124.7 (2C, C-ar); 10.2 (C-furil); 107.9 (2C, C-ar); 1 10.6 (C-furil); 69.2 (O-CH ₂ -ar); 67.6 (O-CH ₂ -CH ₃ ); 65.2 (2C, O-CH ₂ -CH ₃ ); 16.0 (O-CH ₂ - CH ₃ ); 15.4 (2C, O-CH ₂ -CH ₃ ). HPLC: purity = 97%. MS (ES): m / z = 223. Elemental analysis for C ₂₄ H ₂₅ NO ₈ : theoretical% C 63.29% H 5.53% N 3.08; found% C 63.01% H 5.60% N 3.38.

3,4,5-Triethoxybenzyl 5- (2,4-dichlorophenyl) -2-furoate (MR 1.60): Obtained according to the general methodology described above. Reagents: alcohol 3,4,5- triethoxybenzyl (162 μΙ, 0.65 mmol), 5- (2,4-dichlorophenyl) -2-furoic acid (200 mg, 0.78 mmol), PyBOP (505 mg, 0.97 mmol), TEA (179 μΙ, 1 .30 mmol) . Reaction time: 24 hours. Purification: eluent hexane / ethyl acetate (8: 1). Yield: white solid (200 mg, 64%). Mp = 92.4 ° C. ¹ H-NMR (300 MHz, CDCI ₃ ) δ 7.93 (d, J = 8.6 Hz, 1 H, H-ar); 7.48 (d, J = 2.0 Hz, 1 H, H-ar); 7.33 (dd, J = 8.6 and 2.1 Hz, 1 H, H-ar); 7.28 (d, J = 3.7 Hz, 1 H, H-fury); 7.20 (d, J = 3.7 Hz, 1 H, H-fury), 6.65 (s, 2H, H-ar); 5.26 (s, 2H, O-CH ₂ -ar); 4.07 (m, 6H, O-CÜCH3); 1.43 (t, J = 6.9 Hz, 6H, O-CH ₂ CH ₃ ); 1.35 (t, J = 6.0 Hz, 3H, O-CH ₂ CH ₃ ). ¹³ C-NMR (75 MHz, CDCI ₃ ) δ 158.8 (CO); 153.4 (2C, C-ar); 153.2 (C-ar); 144.0 (C-furil); 138.5 (C-furil); 135.2 (C-ar); 132.0 (C-ar); 131 (C-ar); 130.0 (C-ar); 127.9 (C-ar); 127.0 (C-ar); 120.2 (C-furil); 1 13.1 (C-furil); 107.7 (2C, C-ar); 69.3 (O-CH ₂ CH ₃ ); 67.4 (0-CH ₂ -ar); 65.1 (2C, O-CH ₂ CH ₃ ); 15.6 (0-CH ₂ - CH ₃ ); 14.9 (2C, 0-CH ₂ -CH ₃ ). HPLC: purity = 93%. MS (ES): m / z = 501 (M + Na) ⁺ . Elemental analysis for C ₂₄ H ₂₄ CI ₂ 0 ₆ : theoretical% C 60.13% H 5.05% CI 14.79; found% C 60.25% H 4.98% CI 14.56.

2 -furo 3,4,5-trimethoxybenzyl ato (MR 2.38):

 MR 2.38

It is obtained according to the methodology described above. Reagents: 3,4,5-trimethoxybenzyl alcohol (373 μΙ, 2.25 mmol), 2-furoic acid (300 mg, 2.62 mmol), PyBOP (1.36 g, 2.62 mmol), TEA (622 μΙ, 4.50 mmol). Reaction time: 24 hours. Purification: eluent hexane / ethyl acetate (3: 1). Yield: white solid (173 mg, 27%). ¹ H-NMR (CDCI ₃ , 300 MHz) δ 7.56 (d, J = 1 .7 Hz, 1 H, H-fury); 7.19 (d, J = 4.3 Hz, 1 H, H-fury); 6.65 (s, 2H, H-ar); 6.48 (d, J = 3.5 Hz, 1 H, rifle); 5.24 (s, 2H, O-CH ₂ -ar); 3.84 (s, 6H, O-CH ₃ ); 3.82 (s, 3H, O-CH3). C-NMR (CDCI3, 75 MHz) δ 158.9 (CO); 153.7 (C-ar, 2C); 146.9 (C-furil); 144.91 (C-furil); 138.5 (C-ar); 131.9 (C-furil); 1 18.7 (C-furil); 1 12.3 (C-furil); 106.2 (C-ar, 2C); 67.2 (O-CH ₂ -ar); 61 .21 (0-CH ₃ ); 56.4 (0-CH ₃ ). HPLC: purity = 97%. MS (ES): m / z = 181. Elemental analysis for Ci ₅ Hi ₆ 0 ₆ : theoretical% C 61 .64% H 5.52, found% C 61 .50% H 5.30.

Synthesis of derivatives of A - (3,4,5-trimethoxybenzyl) -5-phenyl-2-furamide

 General method

 On a solution of the corresponding 5-phenyl-2-furoic acid derivative (1.2 equivalents) in 10 ml of dichloromethane, add the PyBOP coupling agent (1.2 equivalent) and stir at room temperature for one hour. Then, 3,4,5-trimethoxybenzylamine (1 equivalent) and TEA (2 equivalents) are added as a base and stirred at room temperature for the time indicated in each case. Finally, the solvent is removed by evaporating under reduced pressure. The obtained residue is purified by silica gel column chromatography using the eluents indicated in each case.

N-(3,4,5-trimetoxibencil)-5-(2-trifluorometilfenil)-2-furamida (MR 2.35): Se obtiene según la metodología general descrita anteriormente. Reactivos: 3,4,5- trimetoxibencilamina (166 μΙ, 0.97 mmol), ácido 5-(2-trifluorometilfenil)-2-furoico (300 mg, 1 .14 mmol), PyBOP (590 mg, 1 .14 mmol), TEA (314 μΙ, 2.27 mmol). Tiempo de reacción: 12 horas. Purificación: eluyente hexano/ acetato de etilo (6:1 ). Rendimiento: sólido blanco (400 mg, 94 %). P.f = 123.7 °C. ¹ H-RMN (CDCI₃, 300 MHz) δ 7.83 (d, J =7.8 Hz, 1 H, H-ar); 7.73 (d, J = 7.8 Hz, 1 H, H-ar); 7.64 (t, J = 7.8 Hz, 1 H, H-ar); 7.53 (t, J = 7.4 Hz, 1 H, H-ar); 7.29 (d, J = 3.5 Hz, 1 H, H-furil); 6.80 (d, J = 3.5 Hz, 1 H, H-furil); 6.61 (s, 2H, H-ar); 4.60 (d, J = 5.8 Hz, 2H, NH-CH₂-ar); 3.87 (s, 3H, OCH₃); 3.89 (s, 6H, OCH₃). ¹³C- RMN (CDCI₃, 75 MHz) δ 158.5 (CO); 153.9 (2C, C-ar); 152.7 (C-furil); 148.2 (C-furil); 137.0 (C-ar); 134.0 (C-ar); 132.4 (C-ar); 130.8 (C-ar); 129.4 (C-ar); 128.9 (c, J = 17.5 Hz, C-CF₃); 127.2 (d, J = 273.5 Hz, CF₃); 1 16.4 (C-furil); 1 12.2 (C-furil); 105.7 (2C, C-ar); 61 .3 (OCH₃); 56.5 (2C, OCH₃); 43.9 (NH-CH₂-ar). HPLC: pureza > 99 %. EM (ES): m/ z = 458 (M+Na)⁺. Análisis elemental para C₂₂H₂₀F3NO₅: teórico: %C 60.69 %H 4.63 % N 3.22 hallado %C 60.48 %H 4.57 %N 3.24.

N- (3,4,5-trimethoxybenzyl) -5- (2-trifluoromethylphenyl) -2-furamide (MR 2.35): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzylamine (166 μΙ, 0.97 mmol), 5- (2-trifluoromethylphenyl) -2-furoic acid (300 mg, 1.14 mmol), PyBOP (590 mg, 1.14 mmol), TEA (314 μΙ, 2.27 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (6: 1). Yield: white solid (400 mg, 94%). Mp = 123.7 ° C. ¹ H-NMR (CDCI ₃ , 300 MHz) δ 7.83 (d, J = 7.8 Hz, 1 H, H-ar); 7.73 (d, J = 7.8 Hz, 1 H, H-ar); 7.64 (t, J = 7.8 Hz, 1 H, H-ar); 7.53 (t, J = 7.4 Hz, 1 H, H-ar); 7.29 (d, J = 3.5 Hz, 1 H, H-furil); 6.80 (d, J = 3.5 Hz, 1 H, H-fury); 6.61 (s, 2H, H-ar); 4.60 (d, J = 5.8 Hz, 2H, NH-CH ₂ -ar); 3.87 (s, 3H, OCH ₃ ); 3.89 (s, 6H, OCH ₃ ). ¹³ C NMR (CDCI _3, 75 MHz) δ 158.5 (CO); 153.9 (2C, C-ar); 152.7 (C-furil); 148.2 (C-furil); 137.0 (C-ar); 134.0 (C-ar); 132.4 (C-ar); 130.8 (C-ar); 129.4 (C-ar); 128.9 (c, J = 17.5 Hz, C-CF ₃ ); 127.2 (d, J = 273.5 Hz, CF ₃ ); 1 16.4 (C-furil); 1 12.2 (C-furil); 105.7 (2C, C-ar); 61 .3 (OCH ₃ ); 56.5 (2C, OCH ₃ ); 43.9 (NH-CH ₂ -ar). HPLC: purity> 99%. MS (ES): m / z = 458 (M + Na) ⁺ . Elemental analysis for C ₂₂ H ₂₀ F3NO ₅ : theoretical:% C 60.69% H 4.63% N 3.22 found% C 60.48% H 4.57% N 3.24.

A - (3,4,5-Trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide (MR 2.36): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzylamine (173 μΙ, 0.99 mmol), 5- (2-nitro-4-methylphenyl) -2-furoic acid (300 mg, 1,19 mmol), PyBOP (618 mg, 1. 19 mmol), TEA (274 μΙ, 1.98 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (3: 1). Yield: pale yellow solid (56 mg, 14%). Mp = 1 14.2 ° C. ¹ H-NMR (CDCI3, 300 MHz) δ 7.49 (d, J = 8.9 Hz, 2H, H-ar); 7.34 (d, J = 8.4 Hz, 1 H, H-ar); 7.15 (d, J = 3.6 Hz, 1 H, H-furil); 6.65 (d, J = 3.6 Hz, 1 H, H-fury); 6.51 (s, 2H; H-ar); 4.48 (d, J = 5.8 Hz, 2H, NH-CHHuril); 3.81 (s, 6H, OCH ₃ ); 3.75 (s, 3H, OCH3); 2.39 (s, 3H, CH ₃ ). ¹³ C-NMR (CDCI _3, 75 MHz) δ 158.2 (CO); 153.9 (2C, C-ar); 150.6 (C-ar); 148.4 (C-furil); 148.2 (C-furil); 141 .1 (C-ar); 137.3 (C-ar); 133.9 (C-ar); 133.2 (C-ar); 125.2 (C-ar); 124.8 (C-ar); 120.7 (C-ar); 1 16.6 (C-furil); 1 1 1 .5 (C-furil); 105.1 (2C, C-ar); 61 .3 (2C, OCH ₃ ); 56.6 (OCH ₃ ); 43.8 (NH-CH ₂ -ar); 21.5 (CH ₃ ). HPLC: purity = 93%. MS (ES): m / z = 427 (M + H) ⁺ . Elemental analysis for C22H22N2O7: theoretical% C 61 .97,% H 5.20% N 6.57; found% C 61 .68,% H 5.28% N 6.84.

W- (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-chlorophenyl) -2-furamide (MR 3.13): Obtained according to the general methodology described above. Reagents: 3,4,5-trimethoxybenzylamine (104 μΙ, 0.59 mmol), 5- (2-nitro-4-chlorophenyl) -2-furoic acid (200 mg, 0.71 mmol), PyBOP (369 mg, 0.71 mmol), TEA (164 μΙ, 1.18 mmol). Reaction time: 12 hours. Purification: eluent hexane / ethyl acetate (6: 1). Yield: yellow solid (299 mg, 94%). Mp = 142.4 ° C. ¹ H-NMR (300 MHz, CDCI3) δ 7.73 (d, J = 1 .8 Hz, 1 H, H-ar); 7.60 (m, 2H, H-ar); 7.23 (d, J = 3.6 Hz, 1 H, H-fury); 6.77 (d, J = 3.6 Hz, 1 H, rifle); 6.57 (s, 2H; H-ar); 5.30 (s, 1 H, NH); 4.55 (d, J = 5.8 Hz, 2H, NH-Chb-ar); 3.87 (s, 6H, OCH ₃ ); 3.83 (s, 3H, OCH3). ¹³ C-NMR (75 MHz, CDCI ₃ ) δ 158.0 (CO); 154.0 (2C, C-ar); 149.3 (C-furil); 148.8 (C-furil); 148.2 (C-ar); 137.8 (C-ar); 135.8 (C-ar); 133.8 (C-ar); 132.7 (C-ar); 130.7 (C-ar); 124.6 (C-ar); 121.8 (C-ar); 1 16.6 (C-furil); 1 12.4 (C-furil); 105.1 (C-ar); 61 .3 (OCH ₃ ); 56.6 (2C, OCH ₃ ); 43.9 (NH-CH ₂ -ar). HPLC: purity> 96%. MS (ES): m / z = 447, 449. Elemental analysis for C ₂ iH ₁₉ CIN20 ₇ : theoretical:% C 56.45% H 4.29% N 6.27% CI 7.93 found% C 56.56% H 4.04% N 6.12% CI 8.28 .

Synthesis of thiophenecarboxylate or thiophenecarboxamide derivatives

MR2.39

3,4,5-Trimethoxybenzyl 5-bromo-2-thiophenecarboxylate (MR 2.37): On a solution of 5-bromo-2-thiophenecarboxylic acid (300 mg, 1.40 mmol) in 10 ml of dichloromethane the agent is added PyBOP coupler (730 mg, 1.40 mmol) and stirred at room temperature for one hour. Then, 3,4,5-trimethoxybenzyl alcohol (239 μΙ, 1.20 mmol) and TEA (332 μΙ, 2.40 mmol) are added as a base and stirred at room temperature for 12 hours. After this time, the solvent is removed by evaporating under reduced pressure. The residue obtained is purified by silica gel column chromatography using hexane / ethyl acetate (6: 1) as eluent. Yield: white solid (378 mg, 81%). Mp = 1 13.5 ° C. ¹ H-NMR (CDCI ₃ , 300 MHZ) δ 7.57 (d, J = 3.9 Hz, H-thienyl); 7.06 (d, J = 3.9 Hz, 1 H, H-thienyl); 6.63 (s, 2H, H-ar); 5.23 (s, 2H, O-CH ₂ -ar); 3.87 (s, 6H, OCH ₃ ); 3.84 (s, 3H, OCH ₃ ). ¹³ C-NMR (CDCI3, 75 MHZ) δ 161 .3 (CO); 153.7 (2C, C-ar); 138.5 (C-ar); 134.3 (C-thienyl); 133.7 (C-thienyl); 131.5 (C-thienyl); 131.4 (C-ar); 120.9 (C-thienyl); 105.9 (2C, C-ar); 67.6 (O-CH ₂ -ar); 61 .3 (OCH ₃ ); 56.6 (2C, OCH ₃ ). HPLC: purity = 93%. MS (ES): m / z = 388 (M + H) ⁺ . Elemental analysis for Ci ₅ Hi ₅ BrS0 ₅ : theoretical% C 46.52% H 3.90% S 8.28% Br 20.63, found% C 46.27% H 3.81% S 8.43% Br 20.62

A - (3,4,5-trimethoxybenzyl) -5-bromo-2-thiophenecarboxamide (MR 2.43): On a solution of 5-bromo-2-thiophenecarboxylic acid (300 mg, 1.40 mmol) in 10 ml of dichloromethane PyBOP coupling agent (730 mg, 1.40 mmol) is added and stirred at room temperature for one hour. Then, 3,4,5-trimethoxybenzylamine (198 μΙ, 1.16 mmol) and TEA (332 μΙ, 2.40 mmol) are added as a base and stirred at room temperature for 12 hours. After this time, the solvent is removed by evaporating under reduced pressure. The obtained residue is purified by silica gel column chromatography using hexane / ethyl acetate (3: 1) as eluent. Yield: white solid (318 mg, 71%). Mp = 147.3 ° C. ¹ H-NMR (CDCI ₃ , 300 MHz) δ 7.37 (d, J = 3.9 Hz, 1 H, H-thienyl); 7.03 (d; J = 3.9 Hz, 1 H, H-thienyl); 6.52 (s, 2H, H-ar); 4.48 (d; J = 5.8 Hz, 2H, NH-CÜ-ar); 3.81 (s, 9H, H-1, OCH ₃ ). ¹³ C-NMR (CDCI3, 75 MHz) δ 161 .3 (CO); 153.7 (2C, C-ar); 140.8 (C-thienyl); 137.5 (C-ar); 134.0 (C-ar); 132.1 (C-thienyl); 128.6 (C-thienyl); 1 18.5 (C-thienyl); 105.3 (2C, C-ar); 61 .2 (OCH ₃ ); 56.4 (2C, OCH ₃ ); 44.66 (NH-CH ₂ -ar). HPLC: purity = 97%. MS (ES): m / z = 181. Elemental analysis for Ci ₅ H ₁₆ BrNSO ₄ : theoretical% C 46.64% H 4.18% N 3.63% S 8.30% Br 20.68 found% C 64.61% H 4.40% N 3.88% S 8.19% Br 20.69.

3,4,5-Trimethoxybenzyl 5-phenyl-2-thiophenecarboxylate (MR 2.39): MR 2.37 (0.100 g, 0.26 mmol), phenylboronic acid derivative (0.032 g, 0.26 mmol) are added in a microwave vial ), Pd (0) tetrakis (0.01 1 g, 0.01 mmol) and Cs ₂ CO3 (0.017 g, 0.05 mmol) as base. Then 2 ml of a DME / H ₂ O solution (6: 1) is added and stirred at 90 ° C under microwave irradiation for two hours. After this time, it Remove solvent by evaporating under reduced pressure. The residue obtained is purified by silica gel column chromatography using hexane / ethyl acetate (6: 1) as eluent. Yield: white solid (0.045 g, 45%). P. f = 109.4 ° C. ¹ H-NMR (CDCI ₃ , 300 MHz) δ 7.80 (d, J = 3.9 Hz, 1 H, H-thienyl); 7.64 (dd, J = 8.3 and 1 .6 Hz, 2H, H-ar); 7.41 -7.35 (m, 3H, H-ar); 7.30 (d, J = 3.94 Hz, 1 H, H-thienyl); 6.68 (s, 2H, H-ar); 5.28 (s, 2H, 0-CH ₂ -ar); 3.89 (s, 6H; OCH ₃ ); 3.86 (s, 3H, OCH3). ¹³ C-NMR (CDCI _3, 75 MHz) δ 162.4 (CO); 153.8 (2C, C-ar); 152.0 (C-thienyl); 131.8 (C-ar); 129.5 (2C, C-ar); 129.3 (C-thiophenyl); 126.6 (2C, C-ar); 124.1 (C-thienyl); 105.9 (2C, C-ar); 67.4 (0-CH ₂ -ar); 61 .3 (OCH3); 56.6 (2C, OCH3). HPLC: purity> 99%. MS (ES): m / z = 181. Elemental analysis for C ₂ i H ₂₀ O ₅ S: theoretical% C 65.61% H 5.24% N 0% S 8.34; found% C 65.33% H 5.14% N 0.2% S 8.60.

PDE7 inhibition measurement PDE-7 inhibition was carried out using a commercial phosphodiesterase activity measurement kit (GE Healthcare Life Sciences, cat # TRKQ7090). The compounds to be evaluated were incubated (in a concentration range of 0.1 nM to 100 μΜ) in the presence of 0.02 U / well of PDE7A1 (Calbiochem cat # 524751) and 0.05 μθϊ of [ ³ H] cAMP, for 20 min at 30 ° C in the test buffer supplied with the kit (total volume = 100 μΙ).

 After this time, 50 μΙ of a 20 mg / ml suspension of Ytrio silicate SPA microspheres was added and kept stirring at room temperature for 60 minutes. The plate was allowed to stand for 20 min and the radioactivity was detected in a scintillation detector (Trilux Microbeta). In all trials, two points in the absence of PDE7A1 (white) and two points with PDE7A1 in the absence of inhibitors (control) were included.

Data analysis: All compounds were initially evaluated at the concentration of 10 μΜ and the percentage inhibition of PDE7A1 was calculated according to the following formula:

% inhibition = ((cpm control - cpm sample) x 100) / (cpm control - white cpm) For those compounds with% inhibition values greater than 45%, their inhibitory potency (IC ₅ 0) was calculated by constructing a concentration-response curve.

 The data was adjusted with the Prism v 2.1 software (GraphPad Software) using a non-linear adjustment.

MR 2.39 384 30,1

MR 2.39 384 30.1

MR 2.50 413 49.5

MR 2.51 437 24.4

Table 1.% PDE7A inhibition of heterocyclic derivatives at 10 μΜ concentration.

Table 2. IC ₅ or heterocyclic derivatives

Measurement of the neuroprotective effect of furan derivatives by nitrite production in primary microglia cultures

Primary microglia cultures are used [Luna-Medina, R .; Cortes-Canteli, M .; Alonso, M .; Santos, A .; Martínez, A .; Perez-Castillo, A., Regulation of inflammatory response in neural cells in vitro by thiadiazolidinones derivatives through peroxisome proliferator-activated receptor gamma activation. J. Biol. Chem. 2005, 280, 21453-21462]. Primary microglia cultures are obtained from the cortex and hippocampus of rats 2 days old post-natal. After dissecting the cortex and hippocampus and cleaning them from meninges, the cells are broken down by mechanical crushing and incubation with 0.25% trypsin / EDTA at 37 ° C for 45 minutes. DMEM with 10% fetal serum is added to stop digestion with trypsin and the tissue is crushed mechanically. It is centrifuged at 800xg / 5 min and the precipitate is washed 3 times in EBSS; finally the cells are resuspended in DMEM plus 10% fetal serum and seeded at a density of 0.5x105 cells / cm ² . They are incubated for 10-12 days after which a monolayer of astrocytes is observed on which the microglia cells slightly adhere. To isolate the microglia cells, the culture flasks are incubated on a rotary shaker at 37 ° C for 4 hours at 250 rpm and the medium containing the microglia is centrifuged at 1500xg / 5 min. Microglia cells are resuspended in DMEM / 10% FBS and seeded at a density of 2-4x10 ⁵ cells / cm ² . After 1 hour of incubation, to allow them to adhere to the plate, they are washed with TD and incubated in DMEM / 10% FBS for 24 hours after which they are used for the various experiments. The degree of purity of these cultures is determined by immunocytochemical studies with antibodies specific for neurons (β-tubulin and MAP2), astrocytes (GFAP), oligodendrocytes (CNPase) and microglia (0X42).

Microglia cell cultures are treated with LPS (10 μg / mi) in the absence and presence of the different compounds. The compounds are added 1 h before the inflammatory stimulus. Subsequently, the corresponding measures of the effect of the compounds on the production of NO (nitric oxide) by the NOS (inducible nitric oxide synthase) are performed as an indicator of neural damage due to inflammatory processes [Kroncke KD; Fehsel K .; Kolb- Bachofen V., Nitric oxide: cytotoxicity versus cytoprotection-how, why, when, and where? Nitric Oxide 1997, 7, 107-120]. For this, after 24 h of incubation, the amount of nitrites, one of the oxidation products of NO, is determined. For this, the method based on the Griess reaction is used]: 100 μΙ of culture supernatant is mixed with 100 μΙ of Griess reagent in a 96-well plate incubating for 15 min at room temperature. Next, the absorbance at 540 nm is measured in a microplate reader. The amount of nitrite produced is determined using a standard curve of sodium nitrite (Figure 1). Measurement of the neuroprotective effect of furan derivatives by nitrite production in primary astroglia cultures

Primary cultures of astroglía are obtained from the cortex and hippocampus of rats of 2 days of postnatal age [Luna-Medina, R .; Cortes-Canteli, M .; Alonso, M .; Santos, A .; Martínez, A .; Perez-Castillo, A., Regulation of inflammatory response in neural cells in vitro by thiadiazolidinones derivatives through peroxisome proliferator-activated receptor gamma activation. J. Biol. Chem. 2005, 280, 21453-21462]. Once the cortex and hippocampus are isolated, the cells are broken down by mechanical crushing and incubation with 0.25% trypsin / EDTA at 37 ° C for 45 minutes. DMEM with 10% fetal serum is added to stop digestion and the tissue is crushed mechanically. It is centrifuged at 800xg / 5 min and the precipitate is washed 3 times in EBSS; finally, the cells are resuspended in DMEM plus 10% fetal serum and seeded at a density of 0.5x10 ⁵ cells / cm2 in FLASK boats of 75cm ² . They are now incubated at 37 ° C and 5% CO ₂ for 10-12 days, period after which the astroglial cells are isolated. For this, the cultures are shaken for 16-18h at 250 rpm and the supernatant is removed. The plates are washed several times with 1X PBS to eliminate possible debris. The astrogly, which is forming a monolayer at the base of the culture pot, is obtained by incubation with 0.25% trypsin / EDTA for 5 minutes at 37 ° C. After lifting the cells, the medium is centrifuged at 1500xg / 10min. The astroglia cells are resuspended in DMEM / 10% FBS and seeded at a density of 2-4x10 ⁵ cells / cm2 for 24 hours, from which they are used for the various experiments. To determine that the isolation of astroglia has been performed correctly, the degree of purity of the cultures is determined by an immunocytochemical analysis with specific antibodies for different cell types: neurons (β-tubulin and MAP2), astrocytes (GFAP), oligodendrocytes (CNPase) and microglia (0X42). Astroglia cell cultures are treated with LPS (10 μg / mi) in the absence and presence of the different compounds. The compounds are added 1 h before the inflammatory stimulus. Subsequently, the corresponding measures of the effect of the compounds on the production of NO (nitric oxide) by the NOS (inducible nitric oxide synthase) are performed as an indicator of neural damage due to inflammatory processes [Kroncke KD; Fehsel K .; Kolb- Bachofen V., Nitric oxide: cytotoxicity versus cytoprotection-how, why, when, and where? Nitric Oxide 1997, 1, 107-120]. For this, after 24 h of incubation, the amount of nitrites, one of the oxidation products of NO, is determined. For this, the method based on the Griess reaction is used]: 100 μΙ of culture supernatant is mixed with 100 μΙ of Griess reagent in a 96-well plate incubated for 15 min at room temperature. Next, the absorbance at 540 nm is measured in a microplate reader. The amount of nitrite produced is determined using a standard curve of sodium nitrite (Figure 2).

Permeability in the central nervous system (CNS using parallel artificial membranes (PAMPA)

The prediction of the permeability of the various compounds on the central nervous system (CNS), passing the hemtoencephalic barrier, was determined using the methodology of parallel artificial membranes (PAMPA) [Di, L .; kerns, EH; Fan, K .; McConnell, OJ; Crankcase, GT "High throughput artificial membrane permeability assay for blood-brain barrier" Eur. J. Med. Chem., 2003, 38 (3), 223-232]. Commercial reference compounds, phosphate buffer at pH = 7.4 (PBS), Ethanol and dodecane were obtained from Sigma, Acros organics, Merck, Aldrich and Fluka commercial houses, respectively. The porcine brain lipid (reference catalog 141 101) was purchased from Avanti Polar Lipids. Both the 96-well donor plate (Multiscreen® IP Sterile Píate membrane PDVF, pore size 0.45 μΜ, catalog reference MAIPS4510) as the 96-well acceptor plate (Multiscreen®, reference catalog MAMCS9610) were purchased at Millipore. In order to filter the samples, PDVF membrane filters (30 mm in diameter, pore size 0.45 μιη) from the Symta commercial house were used. The equipment used to perform ultraviolet absorbance measurements on 96-well plates was a Thermoscientific Multiskan spectrum.

Ten reference compounds were selected, whose hematoencephalic barrier passage is known and public, in order to validate the experiment. Different amounts of them were taken [(3-5 mg of Caffeine, Enoxacin, Hydrocortisone, Desipramine, Ofloxacin, Piroxicam, Testosterone), (12 mg of Promazine) and 25 mg of Verapamil and Atenolol] which were dissolved in ethanol ( 1000 μΙ_). 100 microliters of these solutions were taken and 1400 μΙ_ of EtOH and 3500 μΙ_ of PBS phosphate buffer (pH = 7.4) buffer were added, in order to reach a final concentration of EtOH of 30% in the solution. The solutions were filtered. Subsequently, 180 μΙ of a solution of PBS / EtOH (70/30) was added to each well of the acceptor plate. The donor plate was impregnated with 4 μΙ_ of a solution of the porcine brain lipid dissolved in dodecane (20 mg ml_ ^“1 ). After 5 minutes, 180 μΙ_ of solution of each compound was added on this plate. To assess their penetration into the central nervous system, they were taken between 1-2 mg and dissolved in 1500 μΙ_ of EtOH and 3500 μΙ_ of phosphate buffer PBS (pH = 7.4) buffer, filtered and added to the 96-well donor plate Then the donor plate was placed on the acceptor forming a kind of "sandwich" and they were left incubating for 2h and 30 min at 25 ° C. The passive transport compounds will pass from the donor plate through the porcine brain lipid to the acceptor plate After 2 h and 30 min, the donor plate is carefully removed The concentration and absorbance of both commercial compounds and synthesized derivatives that were evaluated in the acceptor plates and d Onadoras were determined using a UV absorbance reader. Each sample was analyzed for 3 to 5 wavelengths, in 3 wells and in at least 3 independent experiments. The results are the average of the measurements [standard deviation (SD)] of the different experiments performed. Ten commercial reference compounds were used whose penetration into the central nervous system is known, in each experiment in order to validate the method. A good correlation was found between the experimental (Pe) permeability values and those described, Pe (exptl) = 1.1512 (bibl) - 0.8973 (R ² = 0.977) (Figure 3). From this equation and following the pattern described in the literature [Crivori, P .; Cruciani, G .; Testa, B. "Predicting Blood- Brain Barrier Permeation from Three-Dimensional Molecular Structure." J. Med. Chem., 2000, 43, 2204-2216] for the prediction of blood brain barrier permeability, the compounds can be classified as permeable to the central nervous system (CNS) when they have a permeability> 3.71 x 10 ^"6 cm s ^{~ 1.} The results are shown in Table 3, where it can be seen how some of the compounds evaluated are capable of penetrating the blood-brain barrier.

Compound Bibl. Pe (10 ^{~ 6} cm s ^"1 ) ^to Prediction

 Atenolol 0.8 0.3 ± 0.1

 Caffeine 1 .3 0.8 ± 0.4

 Desipramine 12 1 1 .7 + 0.1

 Enoxacin 0.9 0.4 + 0.3

 Hydrocortisone 1 .9 0.5 + 0.2

 Ofloxacino 0.8 0.4 + 0.4

 Piroxicam 2.5 0.5 + 0.3

 Promazine 8.8 1 1 .9 + 0.9

 Testosterone 17 18.7 + 0.4

 Verapamil 16 17.2 + 1 .2

 MR 1 .51 8.1 ± 0.1

MR 2.36 9.4 + 0.4 PBS.EtOH (70:30) used as solvent. ^a Data average ± standard deviation of at least 3 independent experiments. Table 3. Permeability (Pe 10 ^{~ 6} cm s ^"1 ) in the PAMPA-Blood-brain Barrier experiment for 10 commercial compounds, used for the validation of the experiment, and different derivatives synthesized with their corresponding prediction of central nervous system penetration (CNS) ).

Claims

one . A compound of general formula (I), or a tautomer, salt, solvate or prodrug thereof.

(I where each Ri and R2 are the same or different and are independently selected from hydrogen, a substituted or unsubstituted C1-C4 alkyl group, a halogen group, a substituted or unsubstituted C1-C4 haloalkyl group, a nitro group, a -OR3 group in where R3 is selected from hydrogen or a substituted or unsubstituted C1-C4 alkyl group or a group -NR4R ₅ - where R4 and R5 are the same or different and independently selected from H or a C1-C5 alkyl group; X is selected from a group -C = 0, a group -C = S, -O-, a group - NR ₆ - or a group -R7-X ', where R6 is selected from hydrogen or a C1-C3 alkyl group substituted or unsubstituted, where R ₇ is selected from a substituted or unsubstituted C1-C4 alkyl group or a substituted or unsubstituted C ₂ -C ₄ alkenyl group and X 'is selected from a group -C = 0, a group - C = S, -O- or a group -NR ₆ -; Y is selected from a group -C = 0, a group -C = S, -O- a group - NR ₆ - or a group Y'-Re-, where Y 'is selected from a group -C = 0, a group -C = S, -O-, a group -NR ₆ - and Rs is selected from a substituted or unsubstituted C1-C4 alkyl group or a substituted or unsubstituted C2-C4 alkenyl group; Q is selected from -O-, -S-, or -NR ₉ , where Rg is selected from hydrogen or a substituted or unsubstituted C1-C3 alkyl group.  n and m are the same or different and independently select from an integer selected from 1, 2, 3, 4 and 5 with the proviso that the following compounds:  - (5- (2,4-dichorophenyl) furan-2-yl) methyl-3,4,5-triethoxybenzoate.  - (5- (2,3-dichlorophenyl) furan-2-yl) methyl-3,4,5-triethoxybenzoate  - (5- (2-Methyl-4-nitrophenyl) furan-2-yl) methyl-3,4,5-triethoxybenzoate  - (5- (3-Chloro-4-methoxyphenyl) furan-2-yl) methyl-3,4,5-triethoxybenzoate  - N - ((5- (4-bromophenyl) furan-2-yl) methyl) -3,4,5-triethoxybenzamide  - (5- (2,3-dichlorophenyl) furan-2-yl) methyl-3,4,5-trimethoxybenzoate  - (5- (3-Chloro-4-methoxyphenyl) furan-2-yl) methyl-3,4,5-trimethoxybenzoate  - N - ((5- (4-fluorophenyl) furan-2-yl) methyl) -3,4,5-trimethoxybenzamide  - N - ((5- (2,4-dichlorophenyl) furan-2-yl) methyl) -3,4,5-trimethoxybenzamide  - N - ((5- (4-chlorophenyl) furan-2-yl) methyl) -3,4,5-trimethoxybenzamide  - N - ((5- (4-bromophenyl) furan-2-yl) methyl) -3,4,5-trimethoxybenzamide  - N - ((5- (4-bromophenyl) furan-2-yl) methyl) -3,4,5-trimethoxy-2-nitrobenzamide - 3,4,5-trimethoxy-N - ((5-phenylthiophene-2-yl) methyl) benzamide  - 5- (2-fluorophenyl) -N- (3,4,5-trimethoxybenzyl) -2-furancarboxamide  - 5- (2-fluorophenyl) -N- (1 - (3,4,5-trimethoxyphenyl) ethyl) -2-furancarboxamide - 5- (2-fluorophenyl) -N- (1 - (3,4,5-trimethoxyphenyl) ethyl) -2-thiophenecarboxamide - 5- (4-chlorophenyl) -N- (3,4,5-trimethoxybenzyl) - 2-thiophenecarboxamide  - 5- (2-chlorophenyl) -N- (3,4,5-trimethoxybenzyl) -2-furancarboxamide  are not included in the formula (I). 2. A compound of general formula (I) according to claim 1, wherein each R1 is the same or different and is independently selected from hydrogen or a -OR3 group wherein R3 is selected from hydrogen or a substituted or unsubstituted C1-C4 alkyl group replace. 3. A compound of general formula (I) according to any one of claims 1 or 2, wherein n is 3. 4. A compound of general formula (I) according to any one of claims 1 to 3, wherein each R ₂ is the same or different and is independently selected from hydrogen, a nitro group, a Ci-C ₄ haloalkyl group, a Ci alkyl group -C ₂ substituted or unsubstituted, chlorine, fluorine, bromine or an -OR3 group wherein R3 is selected from hydrogen or d- _C4 substituted or unsubstituted alkyl. 5. A compound of general formula (I) according to any one of claims 1 to 4, wherein m is an integer selected from 1 to 2. 6. A compound of general formula (I) according to claim 1, selected from the following list:  -3,4,5-5- (4-nitrophenyl) -2-furylmethyl triethoxybenzoate  -3,4,5-5- (4-methylphenyl) -2-furylmethyl triethoxybenzoate  -3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate  -3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate -3,4,5-5- (2,4-dichlorophenyl) -2-furylmethyl trimethoxybenzoate  -5- (2,4,5-Dichlorophenyl) -2,4,5-trimethoxybenzyl furoate  -5- (4,5-methylphenyl) -2,4,5-trimethoxybenzyl furoate  3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate  -5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate -5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate  -5- (2, 3-Trifluoromethylphenyl) -2,4,5-trimethoxybenzyl furoate  -5- (3,4,5-Trimethoxybenzyl 2-nitro-4-methylphenyl) -2-furoate  -5- (3,4,5-Trimethoxybenzyl-3-trifluoromethylphenyl) -2-furoate  -5- (4,5-methoxyphenyl) -2,4,5-trimethoxybenzyl furoate -5- (3,4,5-Trimethoxybenzyl 2-Chloro-5-trifluoromethylphenyl) -2-furoate  -5- (4,5-methylphenyl) -2,4,5-triethoxybenzyl furoate 3,4,5-triethoxybenzyl-5-phenyl-2-furoate -5- (4-nitrophenyl) -2,4,5-triethoxybenzyl furoate -5- (2,4,5-Dichlorophenyl) -2,4,5-triethoxybenzyl furoate -N- (3,4,5-trimethoxybenzyl) -5- (2-trifluoromethylphenyl) -2-furamide -N- (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide -N- (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-chlorophenyl) -2-furamide 3,4,5-Trimethoxybenzyl-5-phenyl-2-thiophenecarboxylate or a tautomer, salt, solvate or prodrug thereof. 7. A compound of general formula (I) according to claim 1, selected from the following list: -3,4,5-5- (4-nitrophenyl) -2-furylmethyl triethoxybenzoate  -3,4,5-5- (4-methylphenyl) -2-furylmethyl triethoxybenzoate -3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate  -3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate  -3,4,5-5- (2,4-dichlorophenyl) -2-furylmethyl trimethoxybenzoate  -5- (2,4,5-Dichlorophenyl) -2,4,5-trimethoxybenzyl furoate  -5- (4,5-methylphenyl) -2,4,5-trimethoxybenzyl furoate 3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate  -5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate  -5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate  -5- (2, 3-Trifluoromethylphenyl) -2,4,5-trimethoxybenzyl furoate  -5- (3,4,5-Trimethoxybenzyl 2-nitro-4-methylphenyl) -2-furoate -5- (3,4,5-Trimethoxybenzyl-3-trifluoromethylphenyl) -2-furoate  -5- (4,5-methoxyphenyl) -2,4,5-trimethoxybenzyl furoate  -5- (4,5-methylphenyl) -2,4,5-triethoxybenzyl furoate  3,4,5-triethoxybenzyl-5-phenyl-2-furoate  -5- (4-nitrophenyl) -2,4,5-triethoxybenzyl furoate -5- (2,4,5-Dichlorophenyl) -2,4,5-triethoxybenzyl furoate  -N- (3,4,5-trimethoxybenzyl) -5- (2-trifluoromethylphenyl) -2-furamide -A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide -5,5-Phenyl-2-thiophenecarboxylate of 3,4,5-trimethoxybenzyl or a tautomer, salt, solvate or prodrug thereof. 8. A compound of general formula (I) according to claim 1, selected from the following list: -3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate -3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate 3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate  -5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate -5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate -5- (2, 3-Trifluoromethylphenyl) -2,4,5-trimethoxybenzyl furoate -A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide or a tautomer, salt, solvate or prodrug thereof. 9. A pharmaceutical composition comprising a compound of general formula (I) or a tautomer, salt, solvate or prodrug thereof.

(I where each Ri and R2 are the same or different and are independently selected from hydrogen, a substituted or unsubstituted C1-C4 alkyl group, a halogen group, a substituted or unsubstituted C1-C4 haloalkyl group, a nitro group, a -OR3 group in where R3 is selected from hydrogen or a substituted or unsubstituted C1-C4 alkyl group or a group -NR ₄ R ₅ - where R4 and R5 are the same or different and independently selected from H or a C1-C5 alkyl group; X is selected from a group -C = 0, a group -C = S, -O-, a group - NR ₆ - or a group -R7-X ', where R ₆ is selected from hydrogen or a C1-alkyl group C3 substituted or unsubstituted, where R ₇ is selected from a substituted or unsubstituted C1-C4 alkyl group or a substituted or unsubstituted C2-C4 alkenyl group and X 'is selected from a group -C = 0, a group -C = S, -O- or a group -NR ₆ -; Y is selected from a group -C = 0, a group -C = S, -O- a group - NR ₆ - or a group Y'-Rs-, where Y 'is selected from a group -C = 0, a group -C = S, -O-, a group -NR ₆ - and Rs is selected from a substituted or unsubstituted C1-C4 alkyl group or a substituted or unsubstituted C2-C4 alkenyl group; Q is selected from -O-, -S-, or -NR ₉ , where R ₉ is selected from hydrogen or a substituted or unsubstituted C1-C3 alkyl group.  n and m are the same or different and independently select from an integer selected from 1, 2, 3, 4 and 5 and at least one pharmaceutically acceptable carrier, adjuvant and / or vehicle. 10. A pharmaceutical composition according to claim 9, wherein each R1 is the same or different and is independently selected from hydrogen or a group -OR3 wherein _R3 is selected from hydrogen or a C C4 substituted or unsubstituted alkyl. eleven . A pharmaceutical composition according to any of claims 9 or 10, wherein n is 3. 12. A pharmaceutical composition according to any of claims 9 to 1 1, where each F¾ is the same or different and is independently selected from hydrogen, a C1-C4 haloalkyl group, a nitro group, a substituted or unsubstituted C1-C2 alkyl group, chlorine, fluorine, bromine or a -OR3 group in where R3 is selected from hydrogen or a substituted or unsubstituted C1-C4 alkyl group. 13. A pharmaceutical composition according to any of claims 9 to 12, where m is an integer selected between 1 and 2. 14. A pharmaceutical composition according to claim 9, wherein the compound of general formula (I) is selected from the following list:  -3,4,5-5- (4-nitrophenyl) -2-furylmethyl triethoxybenzoate  -3,4,5-5- (4-methylphenyl) -2-furylmethyl triethoxybenzoate  -3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate -3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate  -3,4,5-5- (2,4-dichlorophenyl) -2-furylmethyl trimethoxybenzoate  -5- (2,4,5-Dichlorophenyl) -2,4,5-trimethoxybenzyl furoate (  -5- (4,5-methylphenyl) -2,4,5-trimethoxybenzyl furoate  3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate -5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate  -5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate  -5- (2, 3-Trifluoromethylphenyl) -2,4,5-trimethoxybenzyl furoate  -5- (3,4,5-Trimethoxybenzyl 2-nitro-4-methylphenyl) -2-furoate  -5- (3,4,5-Trimethoxybenzyl-3-trifluoromethylphenyl) -2-furoate -5- (4,5-methoxyphenyl) -2,4,5-trimethoxybenzyl furoate  -5- (3,4,5-Trimethoxybenzyl 2-Chloro-5-trifluoromethylphenyl) -2-furoate  -5- (4,5-methylphenyl) -2,4,5-triethoxybenzyl furoate  3,4,5-triethoxybenzyl-5-phenyl-2-furoate  -5- (4-nitrophenyl) -2,4,5-triethoxybenzyl furoate -5- (2,4,5-Dichlorophenyl) -2,4,5-triethoxybenzyl furoate  -N- (3,4,5-trimethoxybenzyl) -5- (2-trifluoromethylphenyl) -2-furamide -A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide -N- (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-chlorophenyl) -2-furamide 3,4,5-Trimethoxybenzyl-5-phenyl-2-thiophenecarboxylate 15. A pharmaceutical composition according to claim 9, wherein the compound of general formula (I) is selected from the following list: -3,4,5-5- (4-nitrophenyl) -2-furylmethyl triethoxybenzoate  -3,4,5-5- (4-methylphenyl) -2-furylmethyl triethoxybenzoate  -3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate -3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate  -3,4,5-5- (2,4-dichlorophenyl) -2-furylmethyl trimethoxybenzoate  -5- (2,4,5-Dichlorophenyl) -2,4,5-trimethoxybenzyl furoate  -5- (4,5-methylphenyl) -2,4,5-trimethoxybenzyl furoate  3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate -5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate  -5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate  -5- (2, 3-Trifluoromethylphenyl) -2,4,5-trimethoxybenzyl furoate  -5- (3,4,5-Trimethoxybenzyl 2-nitro-4-methylphenyl) -2-furoate  -5- (3,4,5-Trimethoxybenzyl-3-trifluoromethylphenyl) -2-furoate -5- (4,5-methoxyphenyl) -2,4,5-trimethoxybenzyl furoate  -5- (4,5-methylphenyl) -2,4,5-triethoxybenzyl furoate  3,4,5-triethoxybenzyl-5-phenyl-2-furoate  -5- (4-nitrophenyl) -2,4,5-triethoxybenzyl furoate  -5- (2,4,5-Dichlorophenyl) -2,4,5-triethoxybenzyl furoate -N- (3,4,5-trimethoxybenzyl) -5- (2-trifluoromethylphenyl) -2-furamide  -A / - (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide  3,4,5-Trimethoxybenzyl-5-phenyl-2-thiophenecarboxylate 16. A pharmaceutical composition according to claim 9, wherein the compound of general formula (I) is selected from the following list: -3,4,5-5-phenyl-2-furylmethyl triethoxybenzoate -3,4,5-5- (4-nitrophenyl) -2-furylmethyl trimethoxybenzoate 3,4,5-Trimethoxybenzyl-5-phenyl-2-furoate -5- (4-nitrophenyl) -2,4,5-trimethoxybenzyl furoate -5- (3,4,5-Trimethoxybenzyl 2-nitro-4-chlorophenyl) -2-furoate -5- (2, 3-Trifluoromethylphenyl) -2,4,5-trimethoxybenzyl furoate -N- (3,4,5-trimethoxybenzyl) -5- (2-nitro-4-methylphenyl) -2-furamide 17. Use of a compound of general formula (I), or a tautomer, salt, solvate or prodrug thereof, as defined in any of claims 9 to 16, for the preparation of a medicament. 18. Use of the compound of general formula (I), or a tautomer, salt, solvate or prodrug thereof, as defined in any of claims 9 to 16 for the preparation of a medicament. for the treatment and / or prophylaxis of inflammatory, autoimmune, neurodegenerative, neurological and / or movement disorders. 19. Use of a compound of general formula (I), or a salt, solvate or prodrug tautomer thereof, according to claim 18, for the preparation of a medicament for the treatment and / or prophylaxis of inflammatory and / or autoimmune pathologies. 20. Use of compound of general formula (I), or a salt, solvate or prodrug tautomer thereof, according to claim 19, for the preparation of a medicament for the treatment and / or prophylaxis of inflammatory and / or autoimmune pathologies, wherein inflammatory or autoimmune pathology is a pathology selected from the following list: inflammatory bowel disease, inflammatory joint pathologies, atopic dermatitis and other inflammatory dermatological pathologies, neuritis, encephalitis, encephalomyelitis and inflammatory pathologies that affect the central nervous system such as multiple sclerosis, or peripheral, myositis, vasculitis, systemic lupus erythematosus, asthma, chronic obstructive pulmonary disease, infectious diseases that occur with inflammation, Host rejection reactions against grafting, inflammation associated with spinal cord injury, conjunctivitis and inflammatory oculopathies, otitis and mucositis. twenty-one . Use of a compound of general formula (I), or a salt, solvate or prodrug tautomer thereof, according to claim 18, for the preparation of a medicament for the treatment and / or prophylaxis of neurodegenerative and / or neurological pathologies. 22. Use of a compound of general formula (I), or a salt, solvate or prodrug tautomer thereof, according to claim 21, for the preparation of a medicament for the treatment and / or prophylaxis of neurodegenerative and / or neurological pathologies wherein Neurodegenerative and / or neurological pathology is a pathology selected from the following list: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, cerebral ischemia, post-encephalitic parkinsonisms, dystonia, Tourette's syndrome, periodic limbic movement pathologies, syndrome of Restless legs and attention deficit hyperactivity disorders. 23. Use of a compound of general formula (I), or a salt, solvate or prodrug tautomer thereof, according to claim 18, for the preparation of a medicament for the treatment and / or prophylaxis of pathologies that occur with movement disorders . 24. A compound of general formula (II) or a tautomer, salt, solvate prodrugs thereof:

where each Ri is the same or different and is independently selected from hydrogen, a substituted or unsubstituted C1-C4 alkyl group, a halogen group, a substituted or unsubstituted C1-C4 haloalkyl group, a nitro group, an OR3 group wherein R3 is selected from hydrogen or an alkyl group C1-C4 substituted or unsubstituted or -NR4R ₅ group - wherein R4 and R5 are identical or different and is independently selected from H or Ci- C ₅ alkyl; X is selected from a group -C = 0, a group -C = S, -O-, a group - NR ₆ - or a group -R7-X ', where R6 is selected from hydrogen or a C1-C3 alkyl group substituted or unsubstituted, where R ₇ is selected from a substituted or unsubstituted C1-C4 alkyl group or a substituted or unsubstituted C ₂ -C ₄ alkenyl group and X 'is selected from a group -C = 0, a group - C = S, -O- or a group -NR ₆ -; Y is selected from a group -C = 0, a group -C = S, -O- a group - NR ₆ - or a group Y'-Re-, where Y 'is selected from a group -C = 0, a -C = S group, -O-, -NR ₆ group one - and Rs is selected from a C1-C4 substituted or unsubstituted alkenyl group or C ₂ -C 4 substituted or unsubstituted; Q is selected from -O-, -S-, -NH, or -NR ₉ , where Rg is selected from hydrogen or a substituted or unsubstituted C1-C3 alkyl group. K is selected from a substituted or unsubstituted C1-C4 alkyl group, hydrogen or a halogen. If the alkyl group is substituted, it will be at least one hydroxyl group. n is an integer selected from 1, 2, 3, 4 and 5 25. A compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof, according to claim 24, wherein each Ri is the same or different and is independently selected from hydrogen, a halogen group or a -OR3 group in where R3 is selected from hydrogen or a substituted or unsubstituted C1-C4 alkyl group. 26. A compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof, according to any of claims 24 or 25, wherein n is 3. 27. A compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof, according to any of claims 24 to 26, wherein K is hydrogen 28. A compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof, according to any of claims 24 to 26, wherein K is a halogen. 29. A compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof, according to any of claims 24 to 26, wherein K is a substituted alkyl group. 30. A compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof, according to claim 24, which is selected from the following list: - 5- (2,4-Dichlorophenyl) -2-Furyl Methanol - 3,4,5-trimethoxybenzyl 2-furoate  - 3,4,5-Trimethoxybenzyl 5-bromo-2-thiophenecarboxylate - A / - (3,4,5-trimethoxybenzyl) -5-bromo-2-thiophenecarboxamide 31. A compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof, according to claim 24, which is selected from the following list: - 5- (2,4-dichlorophenyl) -2-furyl methanol  - 3,4,5-trimethoxybenzyl 2-furoate 32. A compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof, according to claim 24 which is 5- (2,4-dichlorophenyl) -2-furyl methanol. 33. A pharmaceutical composition comprising the compound of general formula (II) or a tautomer, salt, solvate or prodrug thereof, according to any one of claims 24 to 32 and at least one pharmaceutically acceptable carrier, adjuvant and / or vehicle. 34. Use of the compound of formula (II) or a tautomer, salt, solvate or prodrug thereof, as defined in claim 24, selected from the following list: - 5- (2,4-Dichlorophenyl) -2-Furyl Methanol  - 3,4,5-Trimethoxybenzyl 2-furoate for the preparation of a medicine. 35. Use of the compound of general formula (II), or a tautomer, salt, solvate or prodrug thereof, as defined in claim 24, selected from the following list: - 5- (2,4-dichlorophenyl) -2 -Furylmethanol - 3,4,5-trimethoxybenzyl 2-furoate for the preparation of a medicine for the treatment and / or prophylaxis of inflammatory, autoimmune, neurodegenerative, neurological and / or movement disorders. 36. Use of a compound of general formula (II), or a salt, solvate or prodrug tautomer thereof, according to claim 35, for the preparation of a medicament for the treatment and / or prophylaxis of inflammatory and / or autoimmune pathologies. 37. Use of compound of general formula (II), or a salt, solvate or prodrug tautomer thereof, according to claim 36, for the preparation of a medicament for the treatment and / or prophylaxis of inflammatory and / or autoimmune pathologies, wherein The inflammatory or autoimmune pathology is a pathology selected from the following list: inflammatory bowel disease, inflammatory joint pathologies, atopic dermatitis and other inflammatory dermatological pathologies, neuritis, encephalitis, encephalomyelitis and inflammatory pathologies that affect the central nervous system such as multiple sclerosis, or peripheral, myositis, vasculitis, systemic lupus erythematosus, asthma, chronic obstructive pulmonary disease, infectious diseases that occur with inflammation, host rejection reactions against graft, inflammation associated with spinal cord injury, conjunctivitis and inflammatory oculopathies, otitis and mucositis. 38. Use of a compound of general formula (II), or a salt, solvate or prodrug tautomer thereof, according to claim 35, for the preparation of a medicament for the treatment and / or prophylaxis of neurodegenerative and / or neurological pathologies. 39. Use of a compound of general formula (II), or a salt, solvate or prodrug tautomer thereof, according to claim 38, for the preparation of a medicament for the treatment and / or prophylaxis of neurodegenerative and / or neurological pathologies wherein Neurodegenerative and / or neurological pathology is a pathology selected from the following list: Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, cerebral ischemia, post-encephalitic parkinsonisms, dystonia, Tourette's syndrome, periodic limbic movement pathologies, restless legs syndrome and attention deficit hyperactivity disorders. 40. Use of a compound of general formula (II), or a salt, solvate or prodrug tautomer thereof, according to claim 35, for the preparation of a medicament for the treatment and / or prophylaxis of pathologies that occur with movement disorders .