Structure-based design, synthesis, and profiling of potent and selective neuronal nitric oxide synthase (nNOS) inhibitors with an amidinothiophene hydroxypiperidine scaffold

Abstract

A novel series of nNOS inhibitors with an amidinothiophene-hydroxypiperidine scaffold was designed based on X-ray structures and in-silico models. Three classes of inhibitors with this scaffold were synthesized and tested for their nNOS activity and eNOS selectivity. Compounds with a linear aliphatic amine linker demonstrated a superior property over those with a sulfonamide or an amide-like linker.