Patent ID: 6201132
Filing Date: 2001-03-13
Classification: A61P,C07D,C07F

Abstract:
An inhibitor of DP-IV mediated processes of general formula: ##STR112##n=1 or 2;m=0, 1, or 2;X=CH.sub.2, O, S, SO, SO.sub.2, NH or NR.sub.1, where R.sub.1 =C.sub.1 -C.sub.6 alkyl;--Y=--N, --CH, or .dbd.C, provided that when Y is .dbd.C, the carbonyl group of A is replaced by --CH.dbd. or --CF.dbd.;R=H, CN, CHO, B(OH).sub.2, C.tbd.C--R.sub.7 or CH.dbd.N--R.sub.8,where R.sub.7 =H, F, C.sub.1 -C.sub.6 alkyl, CN, NO.sub.2, OR.sub.9, CO.sub.2 R.sub.9 or COR.sub.9 ; R.sub.9 =C.sub.1 -C.sub.6 alkyl;R.sub.8 =Ph, OH, OR.sub.9, OCOR.sub.9 or OBn; A is attached to Y; and A is ##STR113##when R is H, CN, C.tbd.C--R.sub.7 or CH.dbd.N--R.sub.8where a=1-5; D=--G--(CH.sub.2).sub.b --(R.sub.4).sub.q --R.sub.3 ; G=O, NH, NMe; b=0-12; q=0-5; D.sup.1 =D with G.noteq.O; R.sub.4 =Z--NH--(CH.sub.2).sub.c -- or NH--Z--(CH.sub.2).sub.c -- where c=1-12 and Z=CO, CH.sub.2 or SO.sub.2 ; R.sub.3 =CO.sub.2 H or ester thereof, CONH.sub.2, CONHNH.sub.2, CONR.sub.5 R.sub.6, CONHNR.sub.5 R.sub.6, PO.sub.3 H or ester thereof, SO.sub.3 H, SO.sub.2 NH.sub.2, SO.sub.2 NR.sub.5 R.sub.6, OH, OR.sub.5, substituted or unsubstituted aryl or heteroaryl, NH.sub.2, NR.sub.5 R.sub.6, NHCO.sub.2 R.sub.5, NHSO.sub.2 NR.sub.5 R.sub.6, --NHCOR.sub.5, NH--SO.sub.2 R.sub.5, NH--CH(:NR.sub.5 R.sub.6), NHCONR.sub.5 R.sub.6, sugar, CO-aminosugar, NHCO-aminosugar or NHCS-aminosugar; and R.sub.5 and R.sub.6 are independendy selected from H and lower alkyl, fluoroalkyl, and cycloalkyl groups of up to 8 atoms and aryl, heteroaryl and alkyl heteroaryl groups of up to 11 atoms or R.sub.5 and R.sub.6 may together comprise a chain (C.sub.3 to C.sub.8);or A is ##STR114##wherein R.sup.1 =H or Me, the ring may contain more heteroatoms, E=J--(CH.sub.2).sub.b --(R.sub.4).sub.q --R.sub.3, J=CO, CH.sub.2 or SO.sub.2, and a, b, q, R.sub.3 and R.sub.4 are as defined under (i);or A is ##STR115##wherein R.sub.2 =H or Me, the ring may contain one or more heteroatoms, and L=(CH.sub.2).sub.d --(CO)--(CH.sub.2).sub.b --(R.sub.4).sub.q --R.sub.3 or (CH.sub.2).sub.c --NR.sub.1 --(CH.sub.2).sub.b --(R.sub.4).sub.q --R.sub.3 where r=0 or 1, d=0-4, e=2-4, and b, q, R.sub.3 and R.sub.4 are as defined under (i);and wherein at least one CH.sub.2 group in a side chain may be replaced by a bioisostere thereof or any amide group which connects A and B or which is in a side-chain of A may be placed by an amide bioisostere.