SPIRO-SUBSITUTED GLUTARAMIDE DIURETIC AGENTS

摘要

Compounds of the formula wherein A completes a 4 or 7 membered carbocyclic ring which may be saturated or mono-unsaturated and which may optionally be fused to a further saturated or unsaturated 5 or 6 membered carbocyclic ring; B is (CH2)m wherein m is an integer of from 1 to 3; each of R and R<4> is independently H, C1-C6 alkyl, benzyl or an alternative biolabile ester-forming group; R<1> is H or C1-C4 alkyl; R<2> and R<3> are each independently H, OH, C1-C4 alkyl or C1-C4 alkoxy; and R<5> is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl(C2-C6 alkynyl), C3-C7 cycloalkyl, C3-C7 cycloalkenyl, C1-C6 alkoxy, -NR<6>R<7>, -NR<8>COR<9>, -NR<8>SO2R<9> or a saturated heterocyclic group; or C1-C6 alkyl substituted by one or more substituents chosen from halo, hydroxy, C1-C6 alkoxy, C2-C6 hydroxyalkoxy, C1-C6 alkoxy(C1-C6 alkoxy), C3-C7 cycloalkyl, C3-C7 cycloalkenyl, aryl, aryloxy, arlyoxy(C1-C4 alkoxy), heterocyclyl, heterocyclyloxy, -NR<6>R<7>, -NR<8>COR<9>, -NR<8>SO2R<9>, -CONR<6>R<7>, -SH, -S(O)pR<1><0>, -COR<1><1> or -CO2R<1><2>; wherein R<6> and R<7> are each independently H, C1-C4 alkyl, C3-C7 cycloalkyl (optionally substituted by hydroxy or C1-C4 alkoxy), aryl, aryl(C1-C4 alkyl), C2-C6 alkoxyalkyl, or heterocyclyl; or the two groups R<6> and R<7> are taken together with the nitrogen to which they are attached to form a pyrrolidinyl, piperidino, morpholino, piperazinyl or N-(C1-C4 alkyl)-piperazinyl group; R<8> is H or C1-C4 alkyl; R<9> is C1-C4 alkyl, CF3, aryl, aryl(C1-C4 alkyl), aryl(C1-C4 alkoxy), heterocycyl, C1-C4 alkoxy or NR<6>R<7> wherein R<6> and R<7> are as previously defined; R<1><0> is C1-C4 alkyl, aryl, heterocyclyl or NR<6>R<7> wherein R<6> and R<7> are as previously defined; R<1><1> is C1-C4 alkyl, C3-C7 cycloalkyl, aryl or heterocyclyl; R<1><2> is H or C1-C4 alkyl; and p is 0, 1 or 2; or a pharmaceutically acceptable salts thereof or bioprecursor therefor are diuretic agents having utility in the treatment of hypertension, heart failure, renal insufficiency and in other disorders.