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

被引：201

作者：

Wang, T

Zhang, ZX

Wallace, OB

Deshpande, M

Fang, HQ

Yang, Z

Zadjura, LM

Tweedie, DL

Huang, S

Zhao, F

Ranadive, S

Robinson, BS

Gong, YF

Riccardi, K

Spicer, TP

Deminie, C

Rose, R

Wang, HGH

Blair, WS

Shi, PY

Lin, PF

Colonno, RJ

Meanwell, NA

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Discovery Chem, Wallingford, CT 06492 USA

[2] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Lead Discovery, Wallingford, CT 06492 USA

[3] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Virol, Wallingford, CT 06492 USA

[4] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Analyt Sci, Wallingford, CT 06492 USA

[5] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Metab & Pharmacokinet, Wallingford, CT 06492 USA

[6] Bristol Myers Squibb Co, Pharmaceut Res Inst, Dept Pharmaceut, New Brunswick, NJ 08903 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2003年 / 46卷 / 20期

关键词：

D O I：

10.1021/jm034082o

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：4236 / 4239

页数：4

共 24 条

[1] SYNTHESIS OF 4-AMINO-1-BETA-D-RIBOFURANOSYL-1H-PYRROLO[2,3-B]PYRIDINE (1-DEAZATUBERCIDIN) AS A POTENTIAL ANTI-TUMOR AGENT [J].