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Chemical and Pharmacological Aspects of Heteroaryl-Nitrones

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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 very rapidly oxygen or carbon centered radicals thus generating nitroxide radical species which are more stable and biochemically less harmful than the original radical. However the operational mechanism of nitrones might also go 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 pyridyl-nitrones) no particular attention has been given to this class of molecules. The following review is a survey of the literature reports on this subject from 1980 to 1999. The structures were classified according to the heterocyclic substituent on the nitrone double bond, and documented pharmaceutical features were emphasized. Whenever possible heteroaromatic and related aromatic nitrones were compared.

Keywords: Amyotropics lateral sclerosis; Heteroaryl Nitrones; Imidazolyl Nitrones; Parkinson and alzheimer diseases; Pyridyl nitrones; Reactive oxygen species ROS; Redical induce oxidative damage; Synthesis of hetroaryl nitrones; cerebral ischemias; furyl and thienyl nitrones

Document Type: Review Article


Publication date: 2000-12-01

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  • Current Medicinal Chemistry covers all the latest and outstanding developments in medicinal chemistry and rational drug design. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of the current topics in medicinal chemistry. Current Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments.
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