Patent ID: 6271262
Filing Date: 2001-08-07
Classification: A61P,C07C,C07D

Abstract:
A compound of formula (I) ##STR30##whereinX is --COOH or --CONHOHn is 1, 2, 3 or 4;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 alkynyl,phenyl(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)--,phenyl(C.sub.1 -C.sub.6 alkyl)O(C.sub.1 -C.sub.6 alkyl)--, orphenyl(C.sub.1 -C.sub.6 alkyl)S(C.sub.1 -C.sub.6 alkyl)--groupany one of which may be optionally substituted by C.sub.1 -C.sub.6 alkyl, trifluoromethyl, C.sub.1 -C.sub.6 alkoxy, halo, cyano (--CN), phenyl, or substituted phenyl; orR.sub.3 represents the characterising group of a natural or non-natural .alpha. amino acid in which any functional groups may be protected; provided that R.sub.3 does not comprise a heterocyclic or heteroaryl group,R.sub.8 is hydrogen, C.sub.1 -C.sub.6 alkyl, benzyl, acyl, optionally substituted phenyl, an amino protecting group, or a group --(CH.sub.2).sub.m COZ where m is an integer from 1 to 6, and Z represents OH, C.sub.1 -C.sub.6 alkoxy or --NR.sub.x R.sub.y where R.sub.x, R.sub.y each independently represent hydrogen or C.sub.1 -C.sub.6 alkyl; and; andR.sub.9 is optionally substituted C.sub.1 -C.sub.6 alkyl, cycloalkyl, cycloalkenyl, di-(C.sub.1 -C.sub.6 alkyl)amino, phenyl, or naphthyl, orR.sub.8 and R.sub.9 taken together represent a divalent C.sub.3 -C.sub.6 alkylene or alkenylene group which may optionally be (i) substituted by an oxo group, and/or (ii) substituted by (C.sub.1 -C.sub.6)alkoxy, hydroxy, mercapto, (C.sub.1 -C.sub.6)alkylthio, amino, halo (including fluoro, chloro, bromo and iodo), cyano, trifluoromethyl, nitro, --COOH, --CONH.sub.2, --CONHR.sup.A or --CONR.sup.A R.sup.A wherein R.sup.A is a (C.sub.1 -C.sub.6)alkyl group, and/or (iii) fused to a phenyl group which itself may be substituted;Y is a group of formula (ID) or (IE) ##STR31##wherein:R.sub.4 represents(a) an optionally substituted cycloalkyl or cycloalkenyl ring; or(b) a phenyl or heteroaryl ring which may be fused to a benzene or heteroaryl ring, either or both of which rings may be substituted, and in which any ring nitrogen atom may be oxidised as an N-oxide, or(c) a group --CHR.sup.x R.sup.y wherein R.sup.x and R.sup.y each independently represents an optionally substituted phenyl or heteroaryl ring which may be linked covalently to each other by a bond or by a C.sub.1 -C.sub.4 alkylene or C.sub.2 -C.sub.4 alkenylene bridge;(d) a group of formula --(Z'--O).sub.w --Z wherein Z' is straight or branched C.sub.1 -C.sub.6 alkyl optionally interrupted by one or more non-adjacent S and/or N atoms, w is an integer >1, and no continuous linear sequence of atoms in the group R.sub.4 is >12, or(e) a straight or branched C.sub.1 -C.sub.6 alkyl group, optionally interrupted by one or more non-adjacent S and/or N atoms, which is substituted by at least two substituents of formula --(Z'"").sub.x --(OZ).sub.q wherein Z'"" is straight or branched C.sub.1 -C.sub.6 alkyl optionally interrupted by one or more non-adjacent S and/or N atoms, x is 0 or 1, q is 1 or 2, and no continuous linear sequence of atoms in the group R.sub.4 is >12, or(f) hydrogen, C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.4 perfluoroalkyl, or a group D-(C.sub.1 -C.sub.6 alkyl)--wherein D is hydroxy, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 alkylthio, acylamino, optionally substituted phenyl or heteroaryl, NH.sub.2, or mono- or di-(C.sub.1 -C.sub.6 alkyl)amino or N-morpholino;or R.sub.3 and R.sub.4 taken together represent a divalent chain of formula --C(R.sup.a)(R.sup.b)--A--Alk--wherein R.sup.a and R.sub.b are independently hydrogen or C.sub.1 -C.sub.6 alkyl, A"" is a bond, --O--, --S--, --S--S--, --NH-- or --NR.sup.a -- wherein R.sub.a is C.sub.1 -C.sub.6 alkyl, and Alk is C.sub.1 -C.sub.6 alkylene;R.sub.5 is hydrogen or a C.sub.1 -C.sub.6 alkyl group;R.sub.6 is hydrogen, C.sub.1 -C.sub.6 alkyl, phenyl(C.sub.1 -C.sub.6 alkyl), heterocyclyl(C.sub.1 -C.sub.6 alkyl), optionally substituted phenyl, or optionally substituted heterocyclyl;R.sub.7 is is hydrogen or a C.sub.1 -C.sub.6 alkyl group;or (when R.sub.7 is hydrogen) R.sub.3 and R.sub.7 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.6 and R.sub.7 taken together with the carbon atom to which they are attached form a 5 or 6-membered carbocyclic or heterocyclic ring;or a pharmaceutically acceptable salt, hydrate or solvate thereof.