Discovery of 4-benzoyl-1-[(4-methoxy-1H-pyrrolo[2,3-b]lpyridin-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]lpyridin-3-yl)oxoacetyl]-2-(R)-methylpiperazine (BMS-378806):: A novel HIV-1 attachment inhibitor that interferes with CD4-gp120 interactions
复制标题
DOI：
10.1021/jm034082o
复制
发表时间：
2003-09-25
影响因子：
7.3
通讯作者：
Meanwell, NA
中科院分区：
文献类型：
--
作者：
Wang, T;Zhang, ZX;Meanwell, NA
吲哚衍生物1干扰HIV表面蛋白gp 120与宿主细胞受体CD 4的相互作用。4-氟衍生物2表现出显著增强的效力，并且当作为溶液制剂经口给药时，在大鼠、犬和食蟹猴中具有生物利用度。然而，2的水悬浮液的生物利用度差，表明溶解限制吸收。7-氮杂吲哚衍生物3，BMS-378806，表现出改善的药物特性，同时保留2的HIV-1抑制特性。
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.