Phenyl oxazoles, thiazoles, oxazolines, oxadiazoles and benzoxazole compounds useful as neuro-protective agents

摘要

Compounds of formula (III) may be used to treat Alzheimer's disease, Parkinson's disease, amytrophic lateral sclerosis or cerebral trauma, or they may be used for inhibiting lipid peroxidation and preventing ischemia-induced cell damage. In formula (III); Ar is phenyl, pyridyl, tetrahydronaphthyl, benzofuranyl or chromanyl substituted with 0 to 2 substituents selected from the group of (C1-C6)alkyl, hydroxy and halo; and substituted with either: (i) one or two substituents selected from the group consisting of O(CH2)tR6, C(=O)(CH2)nR6 and (C1-C6 alkyl)R6, (where R6 is NR7R8, morpholin-1-yl, imidazol-1-yl, 4,5-dihydro-1H-imidazol-2-yl, thiomorpholin-1-yl or optionally substituted piperazin-1-yl); and R7 and R8 are each individually hydrogen, (C1-C6)alkyl, (CH2)pOH, (CH2)pOC(=O)R9, (CH2 ) p-piperidyl, (CH2)pS(C1-C6)alkyl, (CH2)pS(C1-C6)alkyl, (CH2)pO(C1-C6)alkyl, (CH2)pS(=O)(C1-C6)alkyl, where R9 is (C1-C6)alkyl); or (ii) two substituents which when taken together with the carbon atoms to which they are attached form a pyridyl or tetrahydropyridyl ring; provided that when substituent pattern (i) is present, the phenyl or pyridyl group of Ar may additionally be substituted with two substituents which when taken together with the carbon atoms to which they are attached form a phenyl ring; ---- represents a double or single bond; X is O or S; Y is CR5'R5, O or S, where R5' is H and R5 is H or OH, or R5 and R5' taken together are =0; Z is CH2 or N; R is H or (C1-C6)alkyl; R1 and R2 are each individually (C1-C6)alkyl, (C1-C6)alkoxy or phenyl; R3 is H or (C1-C6)alkyl or R3 and R4 taken together form a phenyl group with the ring to which they are attached; R4 is hydrogen or OH, or when Y is CHR5, R4 and R5 are each individually H or when taken together form a bond; m is an integer from 0 to 2, both inclusive; q is 0 or 1; n is an integer from 0 to 4 both inclusive; p is an integer from 1 to 6 both inclusive; and t is an integer from 1 to 4 both inclusive.