Tetrazole scaffolds

Tetrazole is a common drug scaffold. It's found, for example, in Losartan, a bi-phenyl tetrazole based drug and angiotensin II receptor antagonist. The figure shows a tetrazole scaffold and electrostatic potential maps:


Tetrazole scaffolds

Three of the four N-atoms on tetrazole are clearly nucleophiles because of the presence of lone pair electrons. The fourth N-atom is apparently shielded by the bonded H-atom. The tetrazole heterocycle should bind strongly to positively charged binding sites, which is in fact what happens in angiotensin receptors. The electrostatic maps show fairly dramatically why this binding should occur.