The postulated binding functions for the active site of Angiotensin Converting Enzyme (A.C.E.), derived in an earlier study, have made possible the design of improved inhibitors. Consequently, (1 S,9S)-9-azepine-1 -carboxylic acid (Cilazapril), and related compounds, have been synthesized. They are very active inhibitors of A.C.E. and are highly potent antihypertensives in vivo. Modulation of the renin-angiotensin system, in particular through inhibition of angiotensin converting enzyme (A.C.E., E.C.3.4.15. l.), has assumed increasing importance in the therapy of hypertension and of congestive heart failure. Clinical investigations, initially with nonapeptide SQ2088 1 * and later with Captopril (1)3 and Enalapril (2)> have established that these potent A.C.E. inhibitors are effective antihypertensives in man.

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Using an earlier model of the favoured orientation of binding functions of angiotensin converting enzyme (ACE) inhibitors, it has been possible to postulate a new, 7,6‐bicyclic system, based on hexahydropyridazine, which might be expected to have high potency. Some members of this system which have been synthesised have been shown to be very active ACE inhibitors, in vitro and in vivo.

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