DIBENZOBICYCLO[2.2.2.]OCTANE ANGIOTENSIN-II RECEPTOR ANTAGONISTS

Most angiotensin II antagonists in the literature contain the biphenyl tetrazole moiety. We now wish to report a new, more rigidized biphenyl replacement, namely the dibenzobicyclo[2.2.2.]octane scaffold. It was designed on the basis of the three-dimensional conformation of the bi phenyltetrazole moiety of losartan, the prototypic angiotensin II anta gonist. This biphenyltetrazole replacement fixes both the imidazole an d the negatively charged (at physiological pH) tetrazole in the same a reas of space where they are located in losartan. Other scaffolds such as a fluorene and Rebek's Cleft are also discussed.