Journal of the Chemical Society Perkin Transactions 1 · 1986 · 100 citations · 0 references
PharmacyMedicinal ChemistryPharmacologyDrug DesignDrug DiscoveryStructure-activity RelationshipsCardiovascular PharmacologyEnzyme InhibitionHypertension PharmacotherapyLead Compound DesignLigand-based DesignStructure-activity Relationship AnalysisActive Site AnalysisActive Site InhibitorsAntihypertensive Drug TherapyAntihypertensive PharmacologyMacrocyclic CompoundsRenin-angiotensin System InhibitorsRenin-angiotensin-aldosterone System InhibitionRenin-angiotensin-aldosterone System Inhibitors
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, (1S,9S)-9-[(1S)-(ethoxycarbonyl)-3-phenylpropylamino]octahydro-10-oxo-6H-pyridazo[1,2-a][1,2]diazepine-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.