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

  • J Med Chem. 2003 Sep 25;46(20):4236-9. doi: 10.1021/jm034082o.
Tao Wang  1 ,  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 Shi ,  Pin-Fang Lin ,  Richard J Colonno ,  Nicholas A Meanwell
Affiliations
  • 1. Department of Discovery Chemistry, The Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, Connecticut 06492, USA.
PMID: 13678401 DOI: 10.1021/jm034082o
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.

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