Patent ID: 6166055
Filing Date: 2000-12-26
Classification: A61P,C07D

Abstract:
A compound of formula (I): ##STR25## wherein R is --NH--C(X.sub.2)--NH--(CR.sub.13 R.sub.14).sub.v --Z; ##STR26## Z is W, HET, optionally substituted C.sub.1-10 alkyl, optionally substituted C.sub.2-10 alkenyl, or optionally substituted C.sub.2-10 alkynyl;X is C(X.sub.1).sub.2, O, N--R.sub.18, C.dbd.O, or S(O).sub.m' ;X.sub.1 is hydrogen, halogen, C.sub.1-10 alkyl, NR.sub.4 R.sub.5, C(O)NR.sub.4 R.sub.5, optionally substituted C.sub.1-10 alkyl, C.sub.1-10 alkoxy, halosubstituted C.sub.1-10 alkoxy, hydroxy, aryl, aryl C.sub.1-4 alkyl, aryloxy, aryl C.sub.1-4 alkyloxy, heteroaryl, heteroaryl C.sub.1-4 alkyl, heterocyclic, heterocyclic C.sub.1-4 alkyl, or heteroaryl C.sub.1-4 alkyloxy;X.sub.2 is .dbd.O,or .dbd.S;A is CH.sub.2, C(O) or C(S); provided that when A is CH.sub.2, X is not C(X.sub.1).sub.2 ;R.sub.1 is independently selected from hydrogen, halogen, nitro, cyano, halosubstituted C.sub.1-10 alkyl, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.1-10 alkoxy, halosubstituted C.sub.1-10 alkoxy, azide, (CR.sub.8 R.sub.8)q S(O).sub.t R.sub.4, hydroxy, hydroxy C.sub.1-10 alkyl, aryl, aryl C.sub.1-4 alkyl, aryloxy, aryl C.sub.1-4 alkyloxy, heteroaryl, heteroaryl C.sub.1-4 alkyl, heterocyclic, heterocyclic C.sub.1-4 alkyl, heteroaryl C.sub.1-4 alkyloxy, aryl C.sub.2-10 alkenyl, heteroaryl C.sub.2-10 alkenyl, heterocyclic C.sub.2-10 alkenyl, (CR.sub.8 R.sub.8)qNR.sub.4 R.sub.5, C.sub.2-10 alkenyl C(O)NR.sub.4 R.sub.5, (CR.sub.8 R.sub.8)q C(O)NR.sub.4 R.sub.5, (CR.sub.8 R.sub.8)q C(O)NR.sub.4 R.sub.10, S(O).sub.3 R.sub.8, (CR.sub.8 R.sub.8)q C(O)R.sub.11, C.sub.2-10 alkenyl C(O)R.sub.11, C.sub.2-10 alkenyl C(O)OR.sub.11, C(O)R.sub.11, (CR.sub.8 R.sub.8)q C(O)OR.sub.12, (CR.sub.8 R.sub.8)q OC(O)R.sub.11, (CR.sub.8 R.sub.8)q NR.sub.4 C(O)R.sub.11, (CR.sub.8 R.sub.8)qC(NR.sub.4)NR.sub.4 R.sub.5 ; (CR.sub.8 R.sub.8)q NR.sub.4 C(NR.sub.5)R.sub.11 ; (CR.sub.8 R.sub.8)q NHS(O).sub.2 R.sub.17, or (CR.sub.8 R.sub.8)q S(O).sub.2 NR.sub.4 R.sub.5, or two R.sub.1 moieties together may form O--(CH.sub.2).sub.s O-- or a 5 to 6 membered saturated or unsaturated ring; and wherein the aryl, heteroaryl and heterocyclic containing rings may all be optionally substituted;n is an integer having a value of 1 to 3;m is an integer having a value of 1 to 3;m' is an integer having a value of 1 or 2;q is O, or an integer having a value of 1 to 10;s is an integer having a value of 1 to 3;t is O, or an integer having a value of 1 or 2;v is O, or an integer having a value of 1 to 4;p is an integer having a value of 1 to 3;HET is an optionally substituted heteroaryl;R.sub.4 and R.sub.5 are independently hydrogen, optionally substituted C.sub.1-4 alkyl, optionally substituted aryl, optionally substituted aryl C.sub.1-4 alkyl, optionally substituted heteroaryl, optionally substituted heteroaryl C.sub.1-4 alkyl, heterocyclic, or heterocyclic C.sub.1-4 alkyl, or R.sub.4 and R.sub.5 together with the nitrogen to which they are attached form a 5 to 7 member ring which may optionally comprise an additional heteroatom selected from O/N/S;Y is independently selected from hydrogen, halogen, nitro, cyano, halosubstituted C.sub.1-10 alkyl, C.sub.1-10 alkyl, C.sub.2-10 alkenyl, C.sub.1-10 alkoxy, halosubstituted C.sub.1-10 alkoxy, azide, (CR.sub.8 R.sub.8)q S(O).sub.t R.sub.4, hydroxy, hydroxyC1-alkyl, aryl, aryl C.sub.1-4 alkyl, aryloxy, arylC.sub.1-4 alkyloxy, heteroaryl, heteroaryl C.sub.1-4 alkyl, heteroaryl C.sub.1-4 alkyloxy, heterocyclic, heterocyclic C.sub.1-4 alkyl, aryl C.sub.2-10 alkenyl, heteroaryl C.sub.2-10 alkenyl, heterocyclic C.sub.2-10 alkenyl, (CR.sub.8 R.sub.8)q NR.sub.4 R.sub.5, C.sub.2-10 alkenyl C(O)NR.sub.4 R.sub.5, (CR.sub.8 R.sub.8)q C(O)NR.sub.4 R.sub.5, (CR.sub.8 R.sub.8)q C(O)NR.sub.4 R.sub.10 , S(O).sub.3 R.sub.8, (CR.sub.8 R.sub.8)q C(O)R.sub.11, C.sub.2-10 alkenyl C(O)R.sub.11, C.sub.2-10 alkenyl C(O)OR.sub.11, (CR.sub.8 R.sub.8)q C(O)OR.sub.12, (CR.sub.8 R.sub.8)q OC(O)R.sub.11,(CR.sub.8 R.sub.8)q NR.sub.4 C(O)R.sub.11, (CR.sub.8 R.sub.8)qC(NR.sub.4)NR.sub.4 R.sub.5, (CR.sub.8 R.sub.8)q NR.sub.4 C(NR.sub.5)R.sub.11, (CR.sub.8 R.sub.8)q NHS(O).sub.2 R.sub.a, or (CR.sub.8 R.sub.8)q S(O).sub.2 NR.sub.4 R.sub.5, or two Y moieties together may form O--(CH.sub.2).sub.s --O or a 5 to 6 membered saturated or unsaturated ring; andwherein the aryl, heteroaryl and heterocyclic containing rings may all be optionally substituted;R.sub.6 and R.sub.7 are independently hydrogen or a C.sub.1-4 alkyl group, or R.sub.6 and R.sub.7 together with the nitrogen to which they are attached form a 5 to 7 member ring which ring may optionally contain an additional heteroatom which heteroatom is selected from oxygen, nitrogen or sulfur;R.sub.8 is independently hydrogen or C.sub.1-4 alkyl;R.sub.10 is C.sub.1-10 alkyl C(O).sub.2 R.sub.8 ;R.sub.11 is hydrogen, C.sub.1-4 alkyl, optionally substituted aryl, optionally substituted aryl C.sub.1-4 alkyl, optionally substituted heteroaryl, optionally substituted heteroarylC.sub.1-4 alkyl, optionally substituted heterocyclic, or optionally substituted heterocyclicC.sub.1-4 alkyl;R.sub.12 is hydrogen, C.sub.1-10 alkyl, optionally substituted aryl, or optionally substituted arylalkyl;R.sub.13 and R.sub.14 are independently hydrogen, optionally substituted C.sub.1-4 alkyl, or one of R.sub.13 and R.sub.14 may be an optionally substituted aryl;R.sub.15 and R.sub.16 are independently hydrogen, or an optionally substituted C.sub.1-4 alkyl;R.sub.17 is C.sub.1-4 alkyl, aryl, arylalkyl, heteroaryl, heteroarylC.sub.1-4 alkyl, heterocyclic, or heterocyclicC.sub.1-4 alkyl, and wherein the aryl, heteroaryl and heterocyclic rings may all be optionally substituted;R.sub.18 is hydrogen, C.sub.1-4 alkyl, aryl, arylC.sub.1-4 alkyl, heteroaryl, heteroarylC.sub.1-4 alkyl, heterocyclic, or heterocyclicC.sub.1-4 alkyl, all of which may be optionally substituted:R.sub.a is NR.sub.6 R.sub.7, alkyl, aryl C.sub.1-4 alkyl, arylC.sub.2-4 alkenyl, heteroaryl, heteroaryl-C.sub.1-4 alkyl, heteroarylC.sub.2-4 alkenyl, heterocyclic. heterocyclicC.sub.14 alkyl, and wherein the aryl, heteroaryl and heterocyclic rings may all be optionally substituted; ##STR27## the E containing ring is optionally selected from ##STR28## the asterix * denoting point of attachment of the ring; or a pharmaceutically acceptable salt thereof.