Angiotensins molecular conformation

Captopril 678 and enalapril 679 are potent angiotensin converting enzyme (ACE) inhibitors used as antihypertensives. Molecular manipulation based on the enzyme model led to the discovery of some perspective bicyclic structures, for example, cilazapril 680 and compound 681, highly active antihypertensives in vivo. Compound 681 belongs to the most potent conformationally restricted ACE inhibitors and is often used as a model for molecular modeling studies <1996JA8231>. 

Flynn et al.- at Merrell Dow Research Institute took the approach of designing an ACE inhibitor that was intended to mimic the three carboxy-terminus amino acids of angiotensin I, the substrate of the enzyme. This tripeptide fragment, N-benzyloxycarbonyl-Phe-His-Leu-OH, is known to be a modest inhibitor of ACE (K 10 M). The authors used molecular modeling to confirm that the tricyclic compound 9 could serve as a conformationally con-... 

Figure 8 Molecular volume overlap programs of Masek et al. as applied to a pair of angiotensin II antagonists. Note that not all the conformers considered in the over lap calculations are shown.

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