Discovery of 4-benzoyl-1-[(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)oxoacetyl]-2-(R) -methylpiperazine (BMS-378806): A novel HIV-1 attachment inhibitor that interferes with CD4-gp120 interactions

Tao Wang, Zhongxing Zhang, Owen B. Wallace, Milind Deshpande, Haiquan Fang, Zheng Yang, Lisa M. Zadjura, Donald L. Tweedie, Stella Huang, Fang Zhao, Sunanda Ranadive, Brett S. Robinson, Yi Fei Gong, Keith Ricarrdi, Timothy P. Spicer, Carol Deminie, Ronald Rose, Hwei Gene Heidi Wang, Wade S. Blair, Pei Yong ShiPin Fang Lin, Richard J. Colonno, Nicholas A. Meanwell

Research output: Contribution to journalArticlepeer-review

183 Scopus citations

Abstract

Indole derivative 1 interferes with the interaction of the HIV surface protein gp120 with the host cell receptor CD4. The 4-fluoro derivative 2 exhibited markedly enhanced potency and was bioavailable in the rat, dog, and cynomolgus monkey when administered orally as a solution formulation. However, aqueous suspensions of 2 were poorly bioavailable, indicative of dissolution-limited absorption. The 7-azaindole derivative 3, BMS-378806, exhibited improved pharmaceutical properties while retaining the HIV-1 inhibitory profile of 2.

Original languageEnglish (US)
Pages (from-to)4236-4239
Number of pages4
JournalJournal of Medicinal Chemistry
Volume46
Issue number20
DOIs
StatePublished - Sep 25 2003
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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