Thiadiazole derivatives for the treatment of neuro-degenerative diseases

A 1,2,4-thiadiazole derivative according to the structural formula (C):

• wherein
• R1, R2, R3, R4 and R5 are each independently selected from the group consisting of hydrogen, C1-4 alkyl, C1-4 alkoxy, aryl, aryloxy, aryl-C1-4 alkyloxy, heteroaryloxy, benzenesulfonate, amino, hydroxy, nitro, trifluoromethyl, trifluoromethoxy and halogen, or any two adjacent substituents selected from the group consisting of R1, R2, R3, R4 and R5 form, together with the phenyl ring carbon atoms to which they are attached, a saturated or unsaturated ring fused to said phenyl ring and having from 5 to 7 ring members, said saturated or unsaturated ring optionally comprising one or two oxygen atoms and being optionally substituted with one or more halogen atoms;
• R7, R8, R9, R10 and R11 are each independently selected from the group consisting of hydrogen, C1-10 alkyl, C1-6 alkoxy, aryl, hydroxy, acetyl, nitro, trifluoromethyl, trifluoromethoxy, mono-C1-6alkylamino, di-C1-6alkylamino, C1-6alkylcarbonyloxy, C1-6 alkylthio, cyano, heterocyclic, benzyloxy, dialkylaminosulfonyl and halogen;
• or any two adjacent substituents selected from the group consisting of R7, R8, R9, R10 and R11 form, together with the phenyl ring carbon atoms to which they are attached, a saturated or unsaturated ring fused to said phenyl ring and having from 5 to 7 ring members, said saturated or unsaturated ring optionally comprising one or two heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen;
• and each of said C1-6 alkyl, C1-6 alkoxy, aryl or fused ring is optionally substituted with one or more halogen atoms;
• R12 and R13 are each independently selected from the group consisting of hydrogen, C1-6 alkyl, aryl-C1-4 alkyl, aryl and N-containing heterocyclic rings, or R12 and R13 together form a C3-6 cycloalkyl or heterocyclic group;
• X is a linking moiety selected from the group consisting of a single bond;
• —C(═O)—;
• —S(═O)2—;
• divalent saturated, ethylenically unsaturated or acetylenically unsaturated non-cyclic hydrocarbon groups comprising from 1 to 6 atoms in the main chain, each of said atoms in the main chain being independently selected from the group consisting of carbon, nitrogen and sulfur, and each of said carbon atoms in the main chain being optionally substituted with one or more substituents independently selected from the group consisting of oxo, thioxo, C1-4 alkyl and halogen, provided that the number of heteroatoms in the main chain of said divalent saturated or unsaturated non-cyclic hydrocarbon group is 0, 1 or 2;
• and divalent saturated or unsaturated heterocyclic groups comprising from 2 to 6 carbon atoms and from 1 to 3 heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen in the said heterocyclic group;
• or X together with one of R7 and R11 forms a saturated or unsaturated ring having from 5 to 7 ring members and being fused to the phenyl ring bearing said one of R7 and R11, said saturated or unsaturated ring optionally comprising one or two heteroatoms independently selected from the group consisting of oxygen, sulfur and nitrogen, and said saturated or unsaturated ring optionally comprising one or more substituents independently selected from the group consisting of C1-4 alkyl and trifluoromethyl;
• n is an integer from 0 to 11;
• R and R′ are each independently selected from hydrogen and C1-4 alkyl;
• and
• R14 and R15 are each independently selected from hydrogen and C1-4alkyl or according to the structural formula (F):
• wherein X, R1, R2, R3, R4, R5, R6, R12, R13, R, R′, R14, R15 and n are as defined with respect to formula (C), and further wherein Het1 is a heteroaryl group optionally substituted with one or more substituents independently selected from the group consisting of halogen, trifluoromethyl, nitro, cyano and C1-10alkyl,
• or a stereoisomer or solvate thereof, or a pharmaceutically acceptable salt thereof.