Acrylamide derivatives useful as inhibitors of mitochondrial permeability transition

摘要

A compound of general formula (I) ** Formula ** in which: W is aryl or heteroaryl; a is 0, 1, 2 or 3; R and R 'are the same or different and, independently of each other, are selected from: hydrogen; halogen; (C1-C3) alkoxy; haloalkoxy (C1-C2); haloalkyl (C1-C2); NR1R2; CN; SO2NH2; or optionally substituted (C1-C6) alkyl, aryl or heteroaryl; R "is independently selected from: halogen; (C1-C3) alkyl; (C1-C3) alkoxy; (C1-C3) alkoxyalkyl; C1-C2 haloalkoxy; (C1-C2) haloalkyl; NR3R4; or (CH2) nX- (CH2) mQ, in which: n, m independently, are 0, 1 or 2; X is a direct bond; O; S; NH; N-alkyl (C1-C3); Q is an optionally substituted aryl, heteroaryl , heterocycloalkyl or cycloalkyl; R1, R2, R3 and R4 are the same or different and, independently of each other, are a hydrogen atom; a (C1-C3) alkyl or, taken together with the nitrogen atom to which they are attached, R1 -N-R2 and R3-N-R4 can form a heterocyclic ring of the formula: ** Formula ** in which: R5 is a hydrogen atom or a (C1-C3) alkyl group, in which any of the groups (C1-C6) alkyl, aryl, heteroaryl, heterocycloalkyl or cycloalkyl may be optionally further substituted in any of its free positions with one or more groups; and in which a cycloalkyl group may have one or more dob carbon-carbon bonds in the ring, as long as the ring does not become aromatic because of its presence; and wherein a heterocycloalkyl group may have one or more carbon-carbon double bonds or carbon-heteroatom double bonds in the ring, as long as the ring is not made aromatic by its presence; with the proviso that: (E) -3- (3-hydroxyphenyl) -N- [4 - [[4 - [[(E) -3- (3-hydroxyphenyl) prop-2-enoyl] -amino is excluded ] -phenyl] -methyl] -phenyl] -acrylamide and when W is phenyl, other than 0; when W is phenyl and R is hydrogen, R "is other than chlorine, methyl, isopropyl, CF3 or NH2; when W is indazol-5-yl or pyrid-2-yl, R is other than hydrogen, (C1-C3 alkoxy) ); as well as its isomers, tautomers, racemic forms, enantiomers, diastereomers, epimers, mixtures thereof and pharmaceutically acceptable salts thereof.