Abstract
Most angiotensin II antagonists in the literature contain the biphenyltetrazole 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 biphenyltetrazole moiety of losartan, the prototypic angiotensin II antagonist. This biphenyltetrazole replacement fixes both the imidazole and the negatively charged (at physiological pH) tetrazole in the same areas of space where they are located in losartan. Other scaffolds such as a fluorene and Rebek's Cleft are also discussed.
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