PROCESS FOR PRODUCING GLUTARAMIDE DERIVATIVES SUBSTITUTED WITH CYCLOALKYL GROUP

摘要

Compounds having the formula: wherein A completes a 4 to 7 membered carbocyclic ring which may be saturated or mono-unsaturated and which may optionally be fused to a further carbocyclic ring; B is (CH2)m wherein m is 1 to 3; R and R<4> are H, C1-C6 alkyl, benzyl or biolabile ester-forming groups; R<1> is H or C1-C4 alkyl; R<2> and R<3> are each H, OH, C1-C6 alkyl or C1-C6 alkoxy, or are linked together and are (CH2)r wherein r is 1 to 4; Y is an optional alkylene group of from 1 to 6 carbon atoms which may be straight or branched-chain; and R<5> is R<6>CONR<9>-, R<6>SO2NR<9>-, R<6>CO2-, R<6>CO-, R<6>SOq-, R<7>NR<9>CO-, R<7>NR<9>SO2- or R<7>OCO-; wherein R<6> is a group of the formula R<8>(R<1><0>R<1><1>C-CONR<9>)nR<1><0>R<1><1>C-; R<7> is a group of the formula R<1><0>R<1><1>R<1><2>C- and R<9> is H, C1-C6 alkyl, aryl, C3-C7 cycloalkyl, heterocyclyl, aryl(C1-C6 alkyl) or heterocyclyl(C1-C6 alkyl); wherein R<8> is R<9>CONR<9>-, R<9>SO2NR<9>-, R<1><3>R<1><4>N-(CH2)p-, or R<9>O-, R<1><0> and R<1><1> are H or C1-C6 alkyl; or R<1><0> is H and R<1><1> is C1-C6 alkyl which is substituted by OH, SH, SCH3, NH2, aryl(C1-C6 alkyl)OCONH-, NH2CO-, CO2H, guanidino, aryl, or heterocyclyl; or the two groups R<1><0> and R<1><1> are joined to form a five or 6 membered carbocyclic ring which may be saturated, mono-unsaturated, optionally substituted by C1-C4 alkyl or fused to a further carbocylic ring; or R<8> and R<1><1> are linked to form a 2-(N-COR<9>-4-aminopyrrolidinyl) group; R<1><2> is R<1><3>R<1><4>NCO-, R<9>OCO-, R<9>OCH2- or heterocyclyl, R<1><3> and R<1><4> are H, C1-C6 alkyl, C3-C7 cycloalkyl, aryl, aryl(C1-C6 alkyl), C2-C6 alkoxyalkyl, amino (C1-C6 alkyl), heterocyclyl or heterocyclyl(C1-C6alkyl); or the two groups R<1><3> and R<1><4> form a pyrrolidinyl, piperidino, morpholino, piperazinyl, N-(C1-C4 alkyl) piperazinyl, pyrrolyl, imidazolyl, pyrazolyl or triazolyl group; n is 0 or 1; p is 0 or 1 to 6; and q is 0, 1 or 2; and pharmaceutically acceptable salts thereof and bioprecursors therefor, are diuretic agents of value in the treatment of hypertension, heart failure and renal insufficiency.