Patent ID: 6121308
Filing Date: 2000-09-19
Classification: A61P,C07D

Abstract:
A disubstituted bicyclic heterocycle of the formula ##STR8## wherein X is a nitrogen atom or a methine group optionally substituted by a C.sub.1-3 -alkyl group;R.sub.1 is a hydrogen atom or a C.sub.1-6 -alkyl group;B is an ethylene group optionally substituted by one or two C.sub.1-3 -alkyl groups, wherein a methylene moiety of the ethylene group, which is linked to either the bicyclic heteroaromatic group or the Ar group, is optionally replaced by an oxygen or sulphur atom, or by a sulphinyl, sulphonyl, carbonyl, or --NR.sub.1 -- group, wherein R.sub.1 is as hereinbefore defined, orB is a straight-chained C.sub.3-5 -alkylene group, in which a methylene moiety, which is linked neither to the bicyclic heteroaromatic group nor to the Ar group, is replaced by an --NR.sub.1 -- group, wherein R.sub.1 is as hereinbefore defined;E is a cyano or R.sub.b NH--C(.dbd.NH)-- group, whereinR.sub.b is a hydrogen atom, a hydroxy group, a C.sub.1-3 -alkyl group, or a group which may be cleaved in vivo;Ar is a phenylene or naphthylene group optionally substituted by a fluorine, chlorine, or bromine atom, or by a trifluoromethyl, C.sub.1-3 -alkyl, or C.sub.1-3 -alkoxy group; or a thienylene, thiazolylene, pyridinylene, pyrimidinylene, pyrazinylene, or pyridazinylene group optionally substituted in the carbon skeleton by a C.sub.1-3 -alkyl group; andR.sub.a is a phenyl-C.sub.1-3 -alkoxy group, an amino group, a C.sub.1-3 -alkylamino group substituted at the nitrogen atom by a phenyl-C.sub.1-3 -alkyl group, or an R.sub.3 --CO--R.sub.4 N-- or R.sub.3 --SO.sub.2 --R.sub.4 N-- group whereinR.sub.3 is a C.sub.1-5 -alkyl, phenyl-C.sub.1-3 -alkyl, C.sub.3-7 -cycloalkyl, phenyl, naphthyl, pyridyl, quinolyl, isoquinolyl, tetrahydroquinolyl or tetrahydroisoquinolyl group andR.sub.4 is a hydrogen atom, C.sub.1-5 -alkyl or phenyl-C.sub.1-3 -alkyl group, each of which is substituted in the alkyl moiety by a group which may be converted in vivo into a carboxy group, by a carboxy or tetrazolyl group, by an aminocarbonyl or C.sub.1-3 -alkylaminocarbonyl group, each of which is additionally substituted at the nitrogen atom by a group which may be converted in vivo into a carboxy-C.sub.1-3 -alkyl group or by a carboxy group, a C.sub.2-5 -alkyl group terminally substituted by a di-(C.sub.1-3 -alkyl)-amino group, or a C.sub.3-7 -cycloalkyl group,or a tautomer or pharmaceutically acceptable salt thereof.