COMPOUNDS HAVING DIURETIC ACTIVITY AND ANGIOTENSIN CONVERTING INHIBITORY ACTIVITY,METHODS OF THE PREPARATION THEREOF AND PHARMACEUTICAL COMPOSITIONS CONTAINING THE SAME

摘要

Novel compounds possessing both angiotensin enzyme inhibitory activity and diuretic activity are disclosed. The compounds are represented by the general formula CHEM in which R1, R2, R3, R4, R5 and R6 are hydrogen, alkyl, alkenyl, alkynyl, phenyl-alkyl, and cycloalkyl, and may be the same or different: n is an integer from 0 to 4 inclusive; M is alkenyl, alkynyl, cycloalkyl, cycloalkyl-alkyl, polycycloalkyl, polycycloalkyl-alkyl, aryl, aralkyl, heteroaryl, heteroaryl-alkyl, hetero-cycloalkyl, hetero-cycloalkyl-alkyl, fused aryl-cycloalkyl, fused aryl-cycloalkyl-alkyl, fused heteroaryl-cycloalkyl, fused heteroaryl-cycloalkyl-alkyl, alkoxyalkyl, alkylthioalkyl, alkylamino-alkyl, or dialkylaminoalkyl, or M and R6 taken together with the nitrogen to which M is bonded and the carbon to which R6 is bonded from a saturated unsubstituted heterocyclic group containing 3 or 4 ring carbon atoms; Y is hydroxy, alkoxy, amino, or substituted amino, aminoalkanoyl, aryloxy, aminoalkoxy, or hydroxyalkoxy; Z1 and Z2 each is a chemical bond, the group X3-(CH2)m, an amino acid group or the group X3-(CH2)m-X3 wherein X3 is oxygen, sulfur or NH and m is an integer from 0 to 4 inclusive; A and B each is the same as R1 or halogen, trifluoromethyl, OR1, NO2, NR1R2, SO2NH2, CN, SR1, SOR1, SO2R1, CONR1R2, COOR1; C is hydrogen alkyl, heteroallyl, amino, -CR1 = CR2-, CHEM aminoalkyl, furfurylmethylamino, aminorayl or aminobenzyl; X1 and X2 are each S, SO, SO2, NR1, O, chemical bond, (CR9R10)m, -CR9 = CR10-, and CHOH, with the proviso that at least one of X1 and X2 be (CR9R10)m, wherein R9 and R10 are each hydrogen or lower alkyl, and m is an integer from 1 to 5: Ar is a divalent arylene or heteroarylene: and R7 and R8 are