Patent ID: 6310084
Filing Date: 2001-10-30
Classification: A61P,C07C

Abstract:
A compound of general formula (I) ##STR22##wherein:X is a --CO.sub.2 H or --CONHOH group;R.sub.1 is a cycloalkyl, cycloalkenyl or non-aromatic heterocyclic ring containing up to 3 heteroatoms, any of which may be (i) substituted by one or more substituents selected from C.sub.1 -C.sub.6 alkyl, C.sub.2 C.sub.6 alkenyl, halo, cyano (--CN), --CO.sub.2 H, --CO.sub.2 R, --CONH.sub.2, --CONHR, --CON(R).sub.2, --OH, --OR, oxo-, --SH, --SR, --NHCOR and --NHCO.sub.2 R wherein R is C.sub.1 -C.sub.6 alkyl or benzyl and/or (ii) fused to a cycloalkyl or heterocyclic ring;R.sub.2 is a C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl, C.sub.2 -C.sub.12 alkenyl, phenyl(C.sub.1 -C.sub.6 alkyl)-, heteroaryl(C.sub.1 -C.sub.6 alkyl)-, cycloalkyl(C.sub.1 -C.sub.6 alkyl)-, cycloalkenyl(C.sub.1 -C.sub.6 alkyl)-, phenoxy(C.sub.1 -C.sub.6 alkyl)-, heteroaryloxy(C.sub.1 -C.sub.6 alkyl)-, phenyl(C.sub.1 -C.sub.6 alkyl)O(C.sub.1 -C.sub.6 alkyl)-, heteroaryl(C.sub.1 -C.sub.6 alkyl)O(C.sub.1 -C.sub.6 alkyl)-, phenyl(C.sub.1 -C.sub.6 alkyl)S(C.sub.1 -C.sub.6 alkyl)-, or heteroaryl(C.sub.1 -C.sub.6 alkyl)S(C.sub.1 -C.sub.6 alkyl)- group, any one of which may be optionally substituted by C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, halo, cyano (--CN), phenyl, substituted phenyl or heteroaryl.R.sub.3 is C.sub.1 -C.sub.6 alkyl, benzyl, 2,- 3-, or 4-hydroxybenzyl, 2,- 3-, or 4-benzyloxybenzyl, 2,- 3-, or 4-C.sub.1 -C.sub.6 alkoxybenzyl, or benzyloxy(C.sub.1 -C.sub.6 alkyl)-; or the characterizing group of a natural a amino acid, in which any functional group may be protected, any amino group may be acylated and any carboxyl group present may be amidated; ora group --(Alk).sub.n R.sub.6 where Alk is a (C.sub.1 -C.sub.6)alkylene or (C.sub.2 -C.sub.6)alkenylene group optionally interrupted by one or more --O--, or --S-- atoms or --N(R.sub.7)- groups, where R.sub.7 is a hydrogen atom or a (C.sub.1 -C.sub.6)alkyl group, n is 0 or 1, and R.sub.6 is an optionally substituted cycloalkyl or cycloalkenyl group; ora benzyl group subsituted in the phenyl ring by a group of formula --OCH.sub.2 COR.sub.8 wherein R.sub.8 is hydroxyl, amino, (C.sub.1 -C.sub.6)alkoxy, phenyl(C.sub.1 -C.sub.6)alkoxy, (C.sub.1 -C.sub.6)alkylamino, di((C.sub.1 -C.sub.6)alkyl)amino, phenyl(C.sub.1 -C.sub.6)alkylamino, the residue of an amino acid or acid halide, ester or amide derivative thereof, said residue being linked via an amide bond, said amino acid being selected from glycine, .alpha. or .beta. alanine, valine, leucine, isoleucine, phenylalanine, tyrosine, tryptophan, serine, threonine, cysteine, methionine, asparagine, glutamine, lysine, histidine, arginine, glutamic acid, and aspartic acid; ora heterocyclic((C.sub.1 -C.sub.6)alkyl group, either being unsubstituted or mono- or di-substituted in the heterocyclic ring with halo, nitro, carboxy, (C.sub.1 -C.sub.6)alkoxy, cyano, (C.sub.1 -C.sub.6)alkanoyl, trifluoromethyl (C.sub.1 -C.sub.6)alkyl, hydroxy, formyl, amino, (C.sub.1 -C.sub.6)alkylamino, di-(C.sub.1 -C.sub.6)alkylamino, mercapto, (C.sub.1 -C.sub.6)alkylthio, hydroxy(C.sub.1 -C.sub.6)alkyl, mercapto(C.sub.1 -C.sub.6)alkyl or (C.sub.1 -C.sub.6)alkylphenylmethyl; ora group --CR.sub.a R.sub.b R.sub.c in which:each of R.sub.a, R.sub.b and R.sub.c is independently hydrogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.2 C.sub.6)alkenyl, (C.sub.2 -C.sub.6)alkynyl, phenyl(C.sub.1 -C.sub.6)alkyl, (C.sub.3 -C.sub.8)cycloalkyl; orR.sub.c is hydrogen, (C.sub.1 -C.sub.6)alkyl, (C.sub.2 -C.sub.6)alkenyl, (C.sub.2 -C.sub.6)alkynyl, phenyl(C.sub.1 -C.sub.6)alkyl, or (C.sub.3 -C.sub.8)cycloalkyl, and R.sub.a and R.sub.b together with the carbon atom to which they are attached form a 3 to 8 membered cycloalkyl or a 5- to 6-membered heterocyclic ring; orR.sub.a, R.sub.b and R.sub.c together with the carbon atom to which they are attached form a tricyclic ring; orR.sub.a and R.sub.b are each independently (C.sub.1 -C.sub.6)alkyl, (C.sub.2 -C.sub.6)alkenyl, (C.sub.2 -C.sub.6)alkynyl, phenyl (C.sub.1 -C.sub.6)alkyl, or a group as defined for R.sub.c below other than hydrogen, or R.sub.a and R.sub.b together with the carbon atom to which they are attached form a cycloalkyl or heterocyclic ring, and R.sub.c is hydrogen, --OH, --SH, halogen, --CN, --CO.sub.2 H, (C.sub.1 -C.sub.4)perfluoroalkyl, --CH.sub.2 OH, --CO.sub.2 (C.sub.1 -C.sub.6)alkyl, --O(C.sub.1 -C.sub.6)alkyl, --O(C.sub.2 -C.sub.6)alkenyl, --S(C.sub.1 -C.sub.6)alkyl, --SO(C.sub.1 -C.sub.6)alkyl, --SO.sub.2 (C.sub.1 -C.sub.6) alkyl, --S(C.sub.2 -C.sub.6)alkenyl, --SO(C.sub.2 -C.sub.6)alkenyl, --SO.sub.2 (C.sub.2 -C.sub.6)alkenyl or a group --Q--W wherein Q represents a bond or --O--, --S--, --SO--or --SO.sub.2 -- and W represents a phenyl, phenylalkyl, (C.sub.3 -C.sub.8)cycloalkyl, (C.sub.3 -C.sub.8)cycloalkylalkyl, (C.sub.4 -C.sub.8)cycloalkenyl, (C.sub.4 -C.sub.8)cycloalkenylalkyl, heteroaryl or heteroarylalkyl group, which group W may optionally be substituted by one or more substituents independently selected from, hydroxyl, halogen, --CN, --CO.sub.2 H, --CO.sub.2 (C.sub.1 -C.sub.6)alkyl, --CONH.sub.2, --CONH(C.sub.1 -C.sub.6)alkyl, --CONH(C.sub.1 -C.sub.6)alkyl).sub.2, --CHO, --CH.sub.2 OH, (C.sub.1 -C.sub.4)perfluoroalkyl, --O(C.sub.1 -C.sub.6)alkyl, --S(C.sub.1 -C.sub.6)alkyl, --SO(C.sub.1 -C.sub.6)alkyl, --SO.sub.2 (C.sub.1 -C.sub.6)alkyl, --NO.sub.2, --NH.sub.2, --NH(C.sub.1 -C.sub.6)alkyl, --N((C.sub.1 -C.sub.6)alkyl).sub.2, --NHCO(C.sub.1 -C.sub.6)alkyl, (C.sub.1 -C.sub.6)alkyl, (C.sub.2 -C.sub.6)alkenyl, (C.sub.2 -C.sub.6)alkynyl, (C.sub.3 -C.sub.8)cycloalkyl, (C.sub.4 -C.sub.8)cycloalkenyl, phenyl or benzyl;R.sub.4 is hydrogen or a C.sub.1 -C.sub.6 alkyl group, phenyl (C.sub.1 -C.sub.6 alkyl) or heterocyclyl (C.sub.1 -C.sub.6 alkyl);R.sub.5 is hydrogen or a C.sub.1 -C.sub.6 alkyl group;or, when R.sub.5 is hydrogen, R.sub.3 and R.sub.4 taken together with the carbon atoms to which they are attached form a 2-hydroxycyclohexyl or C.sub.6 sugar (hexose) ring;or R.sub.4 and R.sub.5 taken together with the carbon atom to which they are attached form a 5 or 6-members carbocyclic or heterocyclic ring;or a pharmaceutically acceptable salt, hydrate or solvate thereof.