- 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.
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.
Journal of medicinal chemistry (2003-09-19)
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 Shi, Pin-Fang Lin, Richard J Colonno, Nicholas A Meanwell
PMID13678401
ZUSAMMENFASSUNG
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.
MATERIALIEN