Synthesis and Biological Evaluation of Aryl-phospho-indole as Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors
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- 作者：Franc抬ois-Rene虂 Alexandre ; Agne虁s Amador ; Ste虂phanie Bot ; Catherine Caillet ; Thierry Convard ; Jocelyn Jakubik ; Chiara Musiu ; Barbara Poddesu ; Luana Vargiu ; Michel Liuzzi ; Arle虁ne Roland ; Maria Seifer ; David Standring ; Richard Storer ; Cyril B. Dousson
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：January 13, 2011
- 年：2011
- 卷：54
- 期：1
- 页码：392-395
- 全文大小：763K
- 年卷期：v.54,no.1(January 13, 2011)
- ISSN：1520-4804
文摘
A novel series of 3-aryl-phospho-indole (API) non-nucleoside reverse transcriptase inhibitors of HIV-1 was developed. Chemical variation in the phosphorus linker led to the discovery of 3-phenyl-methyl-phosphinate-2-carboxamide 14, which possessed excellent potency against wild-type HIV-1 as well as viruses bearing K103N and Y181C single mutants in the reverse transcriptase gene. Chiral separation of the enantiomers showed that only R enantiomer retained the activity. The pharmacokinetic, solubility, and metabolic properties of 14 were assessed.