Recent advances in the medicinal chemistry of taxoids with novel beta-amino acid side chains.
Beta-Amino acids have been recognized as an important class of compounds in the design and synthesis of potential pharmaceutical drugs and also for the study of enzymatic reaction mechanisms. Among the beta-amino acid family, isoserines (alpha-hydroxy-beta-amino acids) are probably the most important members because many of them are potent enzyme inhibitors and they also serve as essential building blocks for biologically and medicinally important molecules such as Taxol. Taxol (paclitaxel) and Taxotère (docetaxel) are currently considered to be the most important drugs in cancer chemotherapy. This review describes recent advances in the chemistry of isoserines and taxoid anticancer agents at the biomedical interface including (i) the development of highly efficient method for the synthesis of isoserine side chains of taxoids and (ii) the synthesis and structure-activity relationship (SAR) study of taxoids featuring discovery and development of the "second generation" taxoid anticancer agents that possess exceptional activities against drug-resistant cancer cells.
Ojima
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I
Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA.
Lin
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S
Wang
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T
D000470:Alkaloids / Q000138:chemical synthesis / Q000737:chemistry*; D003521:Cyclopropanes / Q000737:chemistry; D015195:Drug Design; D005027:Ethylene Oxide / Q000737:chemistry; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry*; D017239:Paclitaxel / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000737:chemistry* / Q000493:pharmacokinetics; D014407:Tumor Cells, Cultured; D047090:beta-Lactams / Q000138:chemical synthesis / Q000737:chemistry
D000470:Alkaloids; D003521:Cyclopropanes; D009842:Oligopeptides; D047090:beta-Lactams; C030797:cyclopropane; D005027:Ethylene Oxide; D017239:Paclitaxel