New heterocyclic amide derivatives useful as cysteine protease inhibitors for treating neurodegenerative diseases, neuronal damage, stroke, cranial trauma, Alzheimer's disease, etc.

摘要

Heterocyclic amide derivatives (I) are new.- DETAILED DESCRIPTION - Heterocyclic amide derivatives of formula (I) and their tautomers, isomers and salts are new: - R1 = phenyl, naphthyl, quinolyl, pyridyl, pyrimidinyl, pyrazinyl, pyridazinyl, quinazolinyl, isoquinolyl, quinoxalinyl, thienyl, benzothienyl, benzofuranyl, furyl or indolyl, all optionally substituted by 1-3 R5 groups; - R2 = Cl, Br, F, 1-6C alkyl, 2-6C alkenyl, 2-6C alkynyl, CF3, (1-6C alkyl)phenyl, (2-6C alkenyl)phenyl, (2-6C alkynyl)phenyl (correction; original text repeats 1-6C alkylphenyl), phenyl, 2-5C alkanoylamino, 1-4C alkylsulfonylamino, benzamido, naphthoylamino, NO2, 1-4C alkoxy or NH2, where the aromatic rings are optionally substituted by 1-2 R5 groups, or two R2 groups form a fused benzene ring optionally substituted by R5; - R3 = 1-6C alkyl optionally substituted by a phenyl, pyridyl or naphthyl group optionally substituted by 1-2 R5 groups; - R5 = H, 1-4C alkyl, 1-4C alkoxy, OH, halogen, CF3, NO2, NH2, CN, COOH, (1-4C alkoxy)carbonyl, 2-5C alkanoyl-amino, benzamido, 1-4C alkylsulfonylamino, phenylsulfonylamino, 1-4C alkylsulfonyl or phenylsulfonyl; - X = a bond; (CH2)m, (CH2)mQ(CH2)o, CH=CH, ethynylene, COCH=CH, NHCOCH=CH, CH=CHCONH, or phenylene monosubstituted by R5; - Q = O, S, SO, SO2, CO, NHCO, CONH, NHSO2 or SO2NH; or - R1-X = a group of formula (i) or (ii): - Y = an unsaturated heterocyclic ring, e.g. pyridine, pyrimidine, pyrazine, imidazole or thiazole; - R4 = H, COOR6 or COZ; - Z = NR7R8 or a group of formula (iii)-(v): - R6 = H, or 1-6C alkyl optionally substituted by phenyl (itself optionally substituted by 1-2 R9 groups); - R7 = H or 1-6C alkyl; - R8 = H, or 1-6C alkyl optionally substituted by phenyl (itself optionally substituted by a R9 group) or by a group of formula (iii)-(v) or by morpholino, 1-R10-4-piperidinyl or (CH2)oNR10R11; - R9 = H, 1-4C alkyl, 1-4C alkoxy, OH, halogen, CF3, NO2, NH2, CN, COOH, (1-4C alkoxy)-carbonyl, 2-5C alkanoyl-amino, benzamido, 1-4C alkylsulfonylamino, phenylsulfonylamino, 1-4C alkylsulfonyl or phenylsulfonyl; - R10, R11 = H, or 1-6C alkyl optionally substituted by phenyl (optionally substituted by 1-2 R9 groups); - n = 0-2; - m, o = 0-4.- ACTIVITY - None given.- MECHANISM OF ACTION - Cysteine protease inhibitor