Design, Synthesis, and in Vitro Evaluation of Cyclic Nitrones as Free Radical Traps for the Treatment of Stroke
Citations Over TimeTop 21% of 1996 papers
Abstract
Analogs of the cyclic nitrone free radical trap 1 (3,3-dimethyl-3,4-dihydroisoquinoline N-oxide, a cyclic analog of phenyl-tert-butylnitrone (PBN)) were prepared in which (1) the fused phenyl ring was replaced with a naphthalene ring, an electron rich heterocycle, or a dimethylphenol, (2) the nitrone-containing ring comprised five, six, or seven atoms, and (3) the gem-dimethyl group was replaced with spirocyclic groups. The most active antioxidant, which bears a dimethylphenol fused to a 7-membered ring nitrone (compound 6h), inhibited lipid peroxidation in vitro with an IC50 of 22 microM, a 75-fold improvement over that of 1. The previously observed correlation between lipophilicity and activity vs lipid peroxidation in vitro has been further substantiated and refined by this study. Moreover, certain classes of compounds (namely, dimethylphenols 6g,h and furan 6j) have now been found which are considerably more active in vitro than expected on the basis of their log k'(w) values.
Related Papers
- → Nitrones. Part IX. The synthesis and reactions of 2,3-dihydro-1,4-oxazine 4-oxide, a heterocyclic nitrone(1968)6 cited
- → A General Synthetic Procedure for N-Unsubstituted Isoxazolidines via Nitrone-Olefin Cycloaddition. Remarkable Catalytic Effect of Bu2SnO(1995)15 cited
- → Nitrones: Novel Strategies in Synthesis(2007)47 cited
- → Stereocontrolled Synthesis of Multi-functionalized β-Substituted α-Amino Acids: Nitrone Cycloaddition Approach(2000)2 cited
- → ИСПОЛЬЗОВAНИЕ ПОТЕНЦИAЛA СОЦИAЛЬНЫХ ПAРТНЕРОВ В ПОДГОТОВКЕ БУДУЩИХ ПЕДAГОГОВ(2024)