Discovery of (5S,6S,9R)-5-Amino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridin-9-yl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-
详细信息 查看全文
- 作者：Guanglin Luo ; Ling Chen ; Charles M. Conway ; Rex Denton ; Deborah Keavy ; Laura Signor ; Walter Kostich ; Kimberley A. Lentz ; Kenneth S. Santone ; Richard Schartman ; Marc Browning ; Gary Tong ; John G. Houston ; Gene M. Dubowchik ; John E. Macor
- 刊名：Journal of Medicinal Chemistry
- 出版年：2012
- 出版时间：December 13, 2012
- 年：2012
- 卷：55
- 期：23
- 页码：10644-10651
- 全文大小：363K
- 年卷期：v.55,no.23(December 13, 2012)
- ISSN：1520-4804
文摘
Calcitonin gene-related peptide (CGRP) receptor antagonists have demonstrated clinical efficacy in the treatment of acute migraine. Herein, we describe the design, synthesis, and preclinical characterization of a highly potent, oral CGRP receptor antagonist BMS-927711 (8). Compound 8 has good oral bioavailability in rat and cynomolgus monkey, attractive overall preclinical properties, and shows dose-dependent activity in a primate model of CGRP-induced facial blood flow. Compound 8 is presently in phase II clinical trials.