INTRODUCTION: Knowledge of NO and its function in cell signaling has rapidly developed since its biological effects were first described in 1977. It is formed from L-arginine by NOS isoforms (nNOS, iNOS and eNOS). These enzymes are products of separate genes, encoded on three different chromosomes and responsible for regulating a variety of functions within cells and tissues. NOS isoforms are currently under investigation as targets for novel therapeutics in especially neurodegenerative disorders, inflammation and pain. Many important questions regarding these messengers and signaling molecules remain to be answered. AREAS COVERED: This review gives an overview of patents covering drug-like inhibitors for the NOS isoforms filed and published within the last 6 years, up to September 2010, as well as insight into recent highlights in this area. EXPERT OPINION: The NOS isoforms are attractive targets in drug design for various pathological conditions and have received considerable interest over recent years. With the advances in molecular biology, modeling software, synthesis, bioassays, and our understanding of the NOS enzymes and the function of NO, novel bioavailable and highly selective drug therapies utilizing this mode of action may soon see the light.
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