Biphenyl tetrazole antagonist

Figure 5.22. Example of pharmacophore feature assignments involving the biphenyl tetrazole "privileged" substructure and the total four-point potential pharmacophores calculated for a GPCR antagonist. Note that just the subset (40%) of the total pharmacophores that contained the "privileged" substructure was used for the library design.

Eprosartan is a non-biphenyl, non-tetrazole competitive antagonist at angiotensin II type 1 (ATi) receptors that is chemically distinct from other angiotensin II receptor antagonists (1). It causes dual blockade of ATi receptors both presynaptically and postsynaptically, reducing sympathetic nerve activity significantly more than other receptor antagonists. 

Furthermore, this procedure can be applied to aryl and alkyl organic nitriles, leading in each case to the formation of tetrazoles in excellent yields. For example, the reaction of a sterically demanding biphenyl nitrile 316 was successful. The resulting tetrazole 317 is a subunit that has become ubiquitous in some of the most potent angiotensin II antagonists (Scheme 66) [226]. 

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