Angiotensin-converting enzyme inhibitors contributions

Imatinib mesylate (Gleevec, Novartis), zanamivir (Relenza, GlaxoSmithKline), and oseltamivir (Tamiflu, Roche) are examples of drugs (Exhibits 3.11 and 3.7) that show the successful contributions of rational drug design. For example, the X-ray structure of angiotensin converting enzyme (ACE) has been reported (see Exhibit 11.2), and this may pave the way for more effective ACE inhibitors to be developed for the treatment of hypertension and heart disorders. 

Angiotensin-converting enzyme (ACE) inhibitors such as captopril exert a long-term reno-protective effect. Among other effects, they lower systemic blood pressure and renal plasma flow and effectively reduce urinary protein excretion. Renal delivery of ACE-inhibitors may increase this efficacy and reduce extra-renal side-effects. Renal targeting of an ACE-in-hibitor can also be useful in clarifying the contribution of local ACE inhibition to these reno-protective effects. 

Some of the most successful ventures in peptide research took place in laboratories of the pharmaceutical industry. The Lederle Laboratories, with G.W. Anderson, J.R. Vaughan, Jr. and F.M. Callahan as principal investigators, made early contributions to the methodology of synthesis and to the synthesis of hormones such as oxytocin and calcitonin. The Squibb Institute for Medical Research was the first to report the synthesis of secretin, an effort led by Miklos Bodanszky. More recently the Institute scored a major success with the development of the first medically useful inhibitor of the angiotensin converting enzyme, an intellectually most appealing discovery of M.A. Ondetti (Plate 32). Another Squibb researcher, J.T. Sheehan (1913-1985), should be remembered for... 

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