Chemical and pharmacological aspects of heteroaryl-nitrones

Radical induced oxidative damage is extremely harmful to tissues and organs due to molecular modifications brought to polyunsaturated membrane lipids, proteins and nucleic acids. Oxidative stress is believed to be one of the pathophysiological mechanisms that. operate in neurodegenerative disorders such as cerebral ischemias, amyotrophic lateral sclerosis, Parkinson's and Alzheimer's diseases. Nitrones oppose oxidative challenges by virtue of their ability to trap ver y rapidly oxygen or carbon centered radicals thus generating nitroxide radi cal species which are more stable and biochemically less harmful than the o riginal radical. However the operational mechanism of nitrones might also g o beyond direct scavenging of radicals. The chemical and pharmacological properties of nitrones depend strongly on the connectivity as well as on the type and position of the substituents in the compound's architecture. Heteroaryl-nitrones are known, but except for a few cases (for example pyri dyl-nitrones) no particular attention has been given to this class of molec ules. The following review is a survey of the literature reports on this su bject from 1980 to 1999. The structures were classified according to the he terocyclic substituent on the nitrone double bond, and documented pharmaceu tical features were emphasized. Whenever possible heteroaromatic and relate d aromatic nitrones were compared.