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

François-René Alexandre, Agnès Amador, Stéphanie Bot, Catherine Caillet, Thierry Convard, Jocelyn Jakubik(Idera Pharmaceuticals (United States)), Chiara Musiu(University of Cagliari), Barbara Poddesu(University of Cagliari), Luana Vargiu(University of Cagliari), Michel Liuzzi(University of Cagliari), Arlène Roland, Maria Seifer(Idera Pharmaceuticals (United States)), David N. Standring(Idera Pharmaceuticals (United States)), Richard Storer, Cyril B. Dousson
Journal of Medicinal Chemistry
December 13, 2010
Cited by 178

Abstract

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.


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