Inhibition of degradation of the vasodilator ANP also results in reduced blood pressure. It is believed that a greater reduction of blood pressure can be achieved with a drug like Omapatrilat that has an effect on two targets that both lower blood pressure. The starting point for the discovery of Omapatrilat dates back to 1968, when an ACE program was started at Squibb in order to find a treatment for hypertension. Thiorphan, a selective NEP inhibitor, was discovered in a different research program in the late seventies. The retrosynthesis for Omapatrilat is shown in Scheme 3.
Swern oxidation produces an aldehyde which cyclises to an imine.
Two deprotection steps and a further peptide coupling afford the final target molecule, Omapatrilat. The results of several studies on animals were presented. Omapatrilat was also superior to Captopril in extending the lifetime of cardiomyopathic hamsters. Fifty percent of the Omapatrilat treated animals survived longer than 290 days, compared with 221 days for animals treated with Captopril and 146 days for hamsters that received a placebo. Dr. Freidinger presented an outstanding overview on peptidomimetics and only some aspects of his presentation will be covered in this report.