SPIRO-SUBSTITUTED GLUTARAMIDE DIURETIC AGENTS

摘要

Abstract"Spiro-Substituted Glutaramide Diuretic Agents"Compounds of the formula(I)wherein A completes a 4 to 7 membered carbocyclic ring which maybe saturated or mono-unsaturated and which may optionally be fusedto a further saturated or unsaturated 5 or 6 membered carbocyclicring; B is (CH2)m wherein m is an integer of from 1 to 3; each ofR and R4 is independently H, C1-C5 alkyl, benzyl or an alternativebiolabile ester-forming group; R1 is H or C1-C4 alkyl; R2 and R3are each independently H, OH, C1-C4 alkyl or C1-C4 alkoxy; and R5is C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, aryl(C2-C6 alkynyl),C3-C7 cycloalkyl, C3-C7 cycloalkenyl, C1-C6 alkoxy, -NR6R7,-NR8COR9, -NR9SO2R9 or a saturated heterocyclic group; or C1-C6alkyl substituted by one or more substituents chosen from halo,hydroxy, C1-C6 alkoxy, C2-C6 hydroxyalkoxy, C1-C6 alkoxy (C1-C6alkoxy), C3-C7 cycloalkyl, C3-C7 cycloalkenyl, aryl, aryloxy,aryloxy(C1-C4 alkoxy), heterocyclyl, heterocyclyloxy, -NR6R7,-NR8COR9, -NR8SO2R9, -CONR6R7, -SH, -S(O)pR10, -COR11 or -CO2R12;wherein R6 and R7 are2each independently H, C1-C4 alkyl, C3-C7 cycloalkyl (optionallysubstituted by hydroxy or C1-C4 alkoxy), aryl, aryl(C1-C4 alkyl),C2-C6 alkoxyalkyl, or heterocyclyl; or the two groups R6 and Rare taken together with the nitrogen to which they are attached toform a pyrrolidinyl, piperidino, morpholino, piperazinyl orN-(C1-C4 alkyl)piperazinyl group; R8 is H or C1-C4 alkyl; R9 isC1-C4 alkyl, CF3, aryl, aryl(C1-C4 alkyl), aryl(C1-C4 alkoxy),heterocycyl, C1-C4 alkoxy or NR6R7 wherein R6 and R7 are aspreviously defined; R10 is C1-C4 alkyl, aryl, heterocyclyl orNR6R7 wherein R6 and R7 are as previously defined; R11 is C1-C4alkyl, C3-C7 cycloalkyl, aryl or heterocyclyl; R12 is H or C1-C4alkyl; and p is 0, 1 or 2; and pharmaceutically acceptable saltsthereof and bioprecursors therefor are diuretic agents havingutility in the treatment of hypertension, heart failure, renalinsufficiency and in other disorders.