Patent ID: 6218379
Filing Date: 2001-04-17
Classification: A61P,C07D,Y02P

Abstract:
A compound of formula I ##STR98##whereinR is hydrogen, unsubstituted lower (cyclo)alkyl or lower (cyclo)alkyl substituted by carboxy, lower alkoxycarbonyl, carbamoyl, lower alkylcarbamoyl, phenylcarbamoyl or hydroxyphenylcarbamoyl; lower alkenylmethyl; lower alkenylmethoxycarbonyl; formyl; unsubstituted lower (cyclo)alkanoyl; or lower (cyclo)alkanoyl substituted by halogen, cyano, carbamoyl-lower alkoxy, carbamoyl-lower alkylthio or carbamoyl-lower alkylamino, unsubstituted lower (cyclo)alkylsulphonyl; or lower (cyclo)alkylsulphonyl substituted by halogen, cyano, carbamoyl-lower alkoxy, carbamoyl-lower alkylthio or carbamoyl-lower alkylamino; unsubstituted carbamoyl or carbamoyl substituted by lower (cyclo)alkyl, lower alkoxycarbonyl-lower alkyl, benzyloxy-carbonyl-lower alkyl, carboxy-lower alkyl, hydroxyphenyl or carbamoylphenyl; or a ring structure of the formulaQ--X--CO-- (a1)orQ--X--SO.sub.2 -- (a2)Q is a 5- or 6-membered ring optionally containing nitrogen, sulphur and/or oxygen;X is a direct bond or a group --CH.sub.2 --, --CH.sub.2 CH.sub.2 --, --CH.dbd.CH--, --NH--, --NHCH.sub.2 --, --CH.sub.2 NH--, --CH(NH.sub.2)--, --CH.sub.2 CH.sub.2 NH--, --C(.dbd.NOCH.sub.3)--, --OCH.sub.2 -- or --SCH.sub.2 --; andA is a group of formula (b1) or (b2) ##STR99##whereinR.sup.3 is unsubstituted aryl or aryl substituted by one or two substituents selected from halogen, hydroxy, cyano, nitro, lower alkyl, lower alkoxy, aralkyl, --CONR.sup.5 R.sup.6, --CH.sub.2 --CONR.sup.5 R.sup.6, --N(R.sup.6)COOR.sup.7, R.sup.6 CO--, R.sup.6 OCO-- or R.sup.6 COO-- in which R.sup.5 is hydrogen, lower alkyl or lower cycloalkyl; R.sup.6 is hydrogen or lower alkyl; and R.sup.7 is hydrogen, lower alkyl, lower alkenyl or a carboxylic acid protecting group selected from benzhydryl, p-nitrobenzyl, and p-methoxybenzyl; an unsubstituted heterocyclyl which is a 5- or 6-membered ring optionally containing nitrogen, sulfur and/or oxygen; a heterocyclyl which is a 5- or 6-membered ring optionally containing nitrogen, sulfur and/or oxygen substituted by lower alkyl, lower alkoxy, halogen, halo substituted alkyl, amino, mercapto, hydroxyl, carbamoyl, carboxyl, oxo, lower alkylthio, carbamoylmethyl, carbamoylamino, hydroxyphenylcarbamoyl, lower alkanoyloxy, methylamino, dimethylamino, chloroacetylamino, unsubstituted benzyl, lower alkoxy substituted benzyl, halo lower alkoxy substituted benzyl, lower alkenyl substituted phenyl, --CONR.sup.5 R.sup.6, --CH.sub.2 --CONR.sup.5 R.sup.6, --N(R.sup.6)COOR.sup.7, R.sup.6 CO--, R.sup.6 OCO-- or R.sup.6 COO-- in which R.sup.5 is hydrogen, lower alkyl or lower cycloalkyl; R.sup.6 is hydrogen or lower alkyl; and R.sup.7 is hydrogen, lower alkyl, lower alkenyl or a carboxylic acid protecting group selected from benzhydryl, p-nitrobenzyl and p-methoxybenzyl; or a heterocyclyl which is a 5- or 6-membered ring optionally containing nitrogen, sulfur and/or oxygen having a phenyl ring fused thereto, the heterocyclyl thereof being unsubstituted or substituted by lower alkyl, lower alkoxy, halogen, halo substituted alkyl, amino, mercapto, hydroxyl, carbamoyl, carboxyl, oxo, lower alkylthio, carbamoylmethyl, carbamoylamino, hydroxyphenylcarbamoyl, lower alkanoyloxy, methylamino, dimethylamino, chloroacetylamino, unsubstituted benzyl, lower alkoxy substituted benzyl, halo lower alkoxy substituted benzyl, or lower alkenyl substituted phenyl; andR.sup.4 is hydrogen, hydroxy, lower (cyclo)alkyl, lower alkoxy, lower (cyclo)alkenyl, lower alkynyl, aralkyl, aryl, aryloxy, aralkyloxy, heterocyclyl which is a 5- or 6-membered ring optionally containing nitrogen, sulfur and/or oxygen or lower alkyl substituted with a heterocyclyl which is a 5- or 6-membered ring optionally containing nitrogen, sulfur and/or oxygen, with each of lower (cyclo)alkyl, lower alkoxy, lower (cyclo)alkenyl, aralkyl, aryl, aryloxy, aralkyloxy or heterocyclyl ring which is a 5- or 6-membered ring optionally containing nitrogen, sulfur and/or oxygen being unsubstituted or substituted by carboxy, amino, nitro, cyano, lower alkyl, benzyl, lower alkoxy, hydroxy, halogen, --CONR.sup.5 R.sup.6, --CH.sub.2 --CONR.sup.5 R.sup.6, --N(R.sup.6)COOR.sup.7, R.sup.6 CO--, R.sup.6 OCO-- or R.sup.6 COO-- in which R.sup.5 is hydrogen, lower alkyl or lower cycloalkyl; R.sup.6 is hydrogen or lower alkyl; and R.sup.7 is hydrogen, lower alkyl, lower alkenyl or a carboxylic acid protecting group selected from benzhydryl, p-nitrobenzyl, and p-methoxybenzyl; and pharmaceutically compatible, readily hydrolyzable esters thereof selected from lower alkanoyloxyalkyl esters, lower alkoxycarbonyloxyalkyl esters, 1-cyclohexyloxycarbonyloxyethyl ester, (5-methyl-2-oxo-1,3-dioxol-4-yl)-methyl ester, phthalidyl esters, thiophthalidyl esters, lower alkoxymethyl esters, lower alkanoylaminomethyl esters, benzyl esters, cyanomethyl esters, (2,2-dimethyl-1-oxopropoxyl)methyl ester, [2-[(2-mehtylpropoxy)carbonyl]-2-pentenyl]2-(2-methylpropoxy)carbonyl]-2-p entenyl ester, 1-(1-methylethoxy)carbonyl]oxy]ethyl ester and 3-3-dimethyl-2-oxobutyl ester, and salts of these compounds.