Discovery of (5S,6S,9R)-5-aqmino-6-(2,3-difluorophenyl)-6,7,8,9-tetrahydro- 5H-cyclohepta[b]pyridin-9-yl4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl) piperidine-1-carboxylate (BMS-927711): An oral Calcitonin Gene-Related Peptide (CGRP) antagonist in cinical trials for treating migraine

摘要

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.