Patent ID: 6248738
Filing Date: 2001-06-19
Classification: A61P,C07D

Abstract:
A compound of formula (I): ##STR38##or a pharmaceutically acceptable salt thereof, whereinone of R.sup.1 and R.sup.2 is H and the other is N.dbd.C(NH.sub.2).sub.2 or NHC(.dbd.NH)NH.sub.2,R.sup.3 is H, halogen, C.sub.1-6 alkyl optionally substituted by one or more halogen, or C.sub.1-6 alkoxy optionally substituted by one or more halogen,R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are each independently H, OH, halogen, C.sub.1-6 alkyl optionally substituted by one or more substituents independently selected from halogen or OH, C.sub.1-6 alkoxy optionally substituted by one or more halogen, CN, CO(C.sub.1-6 alkyl optionally substituted by one or more halogen), (C.sub.m -alkylene)CO.sub.2 R.sup.8, O(C.sub.n -alkylene)CO.sub.2 R.sup.8, O(C.sub.n -alkylene)CN, (C.sub.n -alkylene)CN,(C.sub.m -alkylene)CONR.sup.9 R.sup.10, (C.sub.m -alkylene)NR.sup.9 COR.sup.10, O(C.sub.n -alkylene)CONR.sup.9 R.sup.10, (C.sub.m -alkylene)NR.sup.9 SO.sub.2 R.sup.11, (C.sub.m -alkylene)S(O).sub.p R.sup.11, (C.sub.m -alkylene)SO.sub.2 NR.sup.9 R.sup.10, CH.dbd.CHCOR.sup.8, CH.dbd.CHCONR.sup.9 R.sup.10, CH.dbd.CHSO.sub.2 R.sup.8, CH.dbd.CHSO.sub.2 NR.sup.9 R.sup.10, CH.dbd.CHSO.sub.2 aryl, ora group of formula X-aryl or X-het,or, where two of R.sup.4, R.sup.5, R.sup.6 and R.sup.7 are attached to adjacent carbon atoms, they can be taken together to form an --O(C.sub.n -alkylene)O-moiety,R.sup.8 is H, C.sub.1-6 alkyl optionally substituted by one or more halogen, or aryl(C.sub.1-6 alkylene),R.sup.9 and R.sup.10 are each independently H, C.sub.1-6 alkyl optionally substituted by one or more halogen, aryl(C.sub.1-6 alkylene), aryl, heteroaryl or heteroaryl(C.sub.1-6 alkylene),or R.sup.9 and R.sup.10 may be linked together by an alkylene moiety to form, with the atoms to which they are attached, a 4- to 7-membered ring optionally incorporating an additional hetero-group selected from an O or S atom or a NR.sup.12 group,R.sup.11 is aryl, heteroaryl, or C.sub.1-6 alkyl optionally substituted by one or more halogen,R.sup.12 is H, C.sub.1-6 alkyl optionally substituted by one or more halogen, or CO(C.sub.1-6 alkyl optionally substituted by one or more halogen),X is a direct link, C.sub.n -alkylene, O, (C.sub.n -alkylene)O, O(C.sub.n -alkylene), CH(OH), C(C.sub.1-6 alkyl)OH, CO, S(O).sub.p (C.sub.m -alkylene), (C.sub.m -alkylene)S(O).sub.p, CH.dbd.CH, or C.tbd.C,""aryl"" is phenyl or naphthyl optionally substituted by one or more substituents independently selected from halogen, C.sub.1-6 alkyl optionally substituted by one or more substituents independently selected from halogen and OH, C.sub.1-6 alkoxy optionally substituted by one or more halogen, CN, O(C.sub.n -alkylene)CN, (C.sub.n -alkylene)CN, CO(C.sub.1-6 alkyl optionally substituted by one or more halogen), (C.sub.m -alkylene)CO.sub.2 R.sup.13,O(C.sub.n -alkylene)CO.sub.2 R.sup.13, (C.sub.m -alkylene)CONR.sup.14 R.sup.15, (C.sub.m -alkylene)NR.sup.14 COR.sup.15, O(C.sub.n -alkylene)CONR.sup.14 R.sup.15, (C.sub.m -alkylene)S(O).sub.p R.sup.13, (C.sub.m -alkylene)SO.sub.2 NR.sup.14 R.sup.15, (C.sub.m -alkylene)NR.sup.14 SO.sub.2 R.sup.16, CH.dbd.CHSO.sub.2 R.sup.13, CH.dbd.CHSO.sub.2 NR.sup.14 R.sup.15, CH.dbd.CHSO.sub.2 aryl.sup.1, CH.dbd.CHCOR.sup.13, and CH.dbd.CHCONR.sup.14 R.sup.15,""heteroaryl"" is an optionally benzo-fused 5- or 6-membered heterocyclic group linked by any available atom in the heterocyclic or benzo-ring (if present), which heterocyclic group is selected from dioxolyl, furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl and pyranyl,said ""heteroaryl"" group being optionally substituted by one or more substituents independently selected from halogen, C.sub.1-6 alkyl optionally substituted by one or more substituents independently selected from halogen or OH, C.sub.1-6 alkoxy optionally substituted by one or more halogen, CN, O(C.sub.n -alkylene)CN, (C.sub.n -alkylene)CN, CO(C.sub.1-6 alkyl optionally substituted by one or more halogen), (C.sub.m -alkylene)CO.sub.2 R.sup.13, O(C.sub.n -alkylene)CO.sub.2 R.sup.13, (C.sub.m -alkylene)CONR.sup.14 R.sup.15, (C.sub.m -alkylene)NR.sup.14 COR.sup.15, O(C.sub.n -alkylene)CONR.sup.14 R.sup.15, (C.sub.m -alkylene)NR SO.sub.2 R.sup.16, (C.sub.m -alkylene)S(O).sub.p R.sup.13, (C.sub.m -alkylene)SO.sub.2 NR.sup.14 R.sup.15, CH.dbd.CHCOR.sup.13, CH.dbd.CHCONR.sup.14 R.sup.15, CH.dbd.CHSO.sub.2 R.sup.13, CH.dbd.CHSO.sub.2 NR.sup.14 R.sup.15, or CH.dbd.CHSO.sub.2 aryl.sup.1,""het"" is an optionally benzo-fused 5- or 6-membered heterocyclic group linked to the ""X"" moiety by any available atom in the heterocyclic or benzo-ring (if present), which heterocyclic group is selected from dioxolyl, dioxolanyl, furyl, thienyl, pyrrolyl, oxazolyl, oxazinyl, thiazinyl, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl and pyranyl, or a fully unsaturated, partially or fully saturated analogue thereof, such ""het"" group being optionally substituted by one or more substituents independently selected from halogen, C.sub.1-6 alkyl optionally substituted by one or more substituents independently selected from halogen and OH, C.sub.1-6 alkoxy optionally substituted by one or more halogen, CN, O(C.sub.n -alkylene)CN, (C.sub.n -alkylene)CN, CO(C.sub.1-6 alkyl optionally substituted by one or more halogen), (C.sub.m -alkylene)CO.sub.2 R.sup.13, O(C.sub.n -alkylene)CO.sub.2 R.sup.13,(C.sub.m -alkylene)CONR.sup.14 R.sup.15, (C.sub.m -alkylene)NR.sup.14 COR.sup.15, O(C.sub.n -alkylene)CONR.sup.14 R.sup.15, (C.sub.m -alkylene)NR.sup.14 SO.sub.2 R.sup.16, (C.sub.m -alkylene)S(O).sub.p R.sup.13, (C.sub.m -alkylene)SO.sub.2 NR.sup.14 R.sup.15, CH.dbd.CHCOR.sup.13, CH.dbd.CHCONR.sup.14 R.sup.15, CH.dbd.CHSO.sub.2 R.sup.13, CH.dbd.CHSO.sub.2 NR.sup.14 R.sup.15, and CH.dbd.CHSO.sub.2 aryl.sup.1,""aryl.sup.1 "" is phenyl or naphthyl optionally substituted by one or more substituents independently selected from halogen, C.sub.1-6 alkyl optionally substituted by one or more substituents independently selected from halogen or OH, C.sub.1-6 alkoxy optionally substituted by one or more halogen, CN, O(C.sub.n -alkylene)CN, (C.sub.n -alkylene)CN, CO(C.sub.1-6 alkyl optionally substituted by one or more halogen), (C.sub.m -alkylene)CO.sub.2 R.sup.13, O(C.sub.n -alkylene)CO.sub.2 R.sup.13, (C.sub.m -alkylene)CONR.sup.14 R.sup.15, (C.sub.m -alkylene)NR.sup.14 COR.sup.15, O(C.sub.n -alkylene)CONR.sup.14 R.sup.15, (C.sub.m -alkylene)S(O).sub.p R.sup.13, (C.sub.m -alkylene)SO.sub.2 NR.sup.14 R.sup.15, (C.sub.m -alkylene)NR.sup.14 SO.sub.2 R.sup.16, CH.dbd.CHSO.sub.2 R.sup.13, CH.dbd.CHSO.sub.2 NR.sup.14 R.sup.15, CH.dbd.CHCOR.sup.13, and CH.dbd.CHCONR.sup.14 R.sup.15,R.sup.13 is H, C.sub.1-6 alkyl optionally substituted by one or more halogen, or aryl.sup.2 (C.sub.1-6 alkylene),R.sup.14 and R.sup.15 are each independently H, C.sub.1-6 alkyl optionally substituted by one or more halogen, aryl.sup.2 (C.sub.1-6 alkylene), aryl.sup.2, heteroaryl.sup.1 or heteroaryl.sup.1 (C.sub.1-6 alkylene),or R.sup.9 and R.sup.10 may be linked together by an alkylene moiety to form, with the atoms to which they are attached, a 4- to 7-membered ring optionally incorporating an additional hetero-group selected from an O or S atom or a NR.sup.12 group,R.sup.16 is aryl.sup.2, heteroaryl.sup.1, or C.sub.1-6 alkyl optionally substituted by one or more halogen,""aryl.sup.2 "" is phenyl or naphthyl optionally substituted by one or more substituents independently selected from halogen, C.sub.1-6 alkyl optionally substituted by one or more substituents independently selected from halogen or OH, C.sub.1-6 alkoxy optionally substituted by one or more halogen, CN, O(C.sub.n -alkylene)CN, (C.sub.n -alkylene)CN, or CO(C.sub.1-6 alkyl optionally substituted by one or more halogen),""heteroaryl.sup.1 "" is an optionally benzo-fused 5- or 6-membered heterocyclic group linked by any available atom in the heterocyclic or benzo-ring (if present), which heterocyclic group is selected from dioxolyl, furyl, thienyl, pyrrolyl, oxazolyl, thiazolyl, isoxazolyl, isothiazolyl, imidazolyl, pyrazolyl, oxadiazolyl, thiadiazolyl, triazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl and pyranyl,said ""heteroaryl.sup.1 "" group being optionally substituted by one or more substituents independently selected from halogen, C.sub.1-6 alkyl optionally substituted by one or more substituents independently selected from halogen or OH, C.sub.1-6 alkoxy optionally substituted by one or more halogen, CN, O(C.sub.n -alkylene)CN, (C.sub.n -alkylene)CN, or CO(C.sub.1-6 alkyl optionally substituted by one or more halogen),wherein the ""C-alkylene"" linking groups in the definitions above are linear or branched, and are optionally substituted by one or more (C.sub.1-6 alkyl optionally substituted by one or more halogen) groups,m is an integer from 0 to 3,n is an integer from 1 to 3, andis an integer from 0 to 2.