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Synthesis and Biological Evaluation of Aryl-phospho-indole as Novel HIV-1 Non-nucleoside Reverse Transcriptase Inhibitors

2010; American Chemical Society; Volume: 54; Issue: 1 Linguagem: Inglês

10.1021/jm101142k

1520-4804

François-René Alexandre, Agnès Amador, Stéphanie Bot, Catherine Caillet, Thierry Convard, Jocelyn Jakubik, Chiara Musiu, Barbara Poddesu, Luana Vargiu, Michel Liuzzi, Arlène Roland, Maria Seifer, David N. Standring, Richard Storer, Cyril B. Dousson,

HIV Research and Treatment

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.