Design and Synthesis of Isotaxel: A Novel Water-Soluble Paclitaxel Prodrug Based on the <i>O</i>–<i>N</i> Intramolecular Acyl Migration Reaction
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- Hayashi Yoshio
- Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University
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- Skwarczynski Mariusz
- Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University
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- Hamada Yoshio
- Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University
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- Sohma Youhei
- Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University
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- Kimura Tooru
- Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University
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- Kiso Yoshiaki
- Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University
Bibliographic Information
- Other Title
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- <i>O</i>–<i>N</i>分子内アシル転移反応に基づいた新規水溶性paclitaxelプロドラッグ
- Isotaxelのデザインと合成
Abstract
Paclitaxel 1, one of the most important chemotherapeutic agents with promising antitumor activity, has a sparing water-solubility. This is one of the major drawbacks of 1, since the detergent required for solubilization of 1 causes hypersensitivity reaction. Previously, we have developed a novel class of "O–N intramolecular acyl migration" -type water-soluble prodrugs of HIV-1 protease inhibitors. Hencewe designed novel water-soluble paclitaxel prodrug, isotaxel 2, which is a 2'-O-benzoyl isoform of paclitaxel. Isotaxel was synthesized via coupling of an oxazolidine derivative of phenylisoserine with a Baccactin III derivative and showed 1,800-fold higher water-solubility than paclitaxel. Parent drug 1 was released promptly and completely through simple pH-dependent chemical mechanism,by means of O-N intramolecular acyl migration, under physiological conditions. Since 2 has no additional functional auxiliaries released during the conversion to 1, this would be a great advantage in toxicology and medical economics.
Journal
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- Proceedings of the Symposium on Progress in Organic Reactions and Syntheses
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Proceedings of the Symposium on Progress in Organic Reactions and Syntheses 29 (0), 126-127, 2003
Division of Organic Chemistry, The Pharmaceutical Society of Japan
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Details 詳細情報について
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- CRID
- 1390001205633359744
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- NII Article ID
- 130006995404
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- Data Source
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- JaLC
- CiNii Articles
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- Abstract License Flag
- Disallowed