Degnan Andrew P, Conway Charles M, Dalterio Richard A, Macci Robert, Mercer Stephen E, Schartman Richard, Xu Cen, Dubowchik Gene M, Macor John E
Neuroscience Discovery Chemistry, Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492-7660, USA.
Bioorg Med Chem Lett. 2009 Jul 1;19(13):3555-8. doi: 10.1016/j.bmcl.2009.04.150. Epub 2009 May 8.
The calcitonin gene-related peptide (CGRP) receptor has been implicated in the pathogenesis of migraine. A class of urethanamide derivatives has been identified as potent inhibitors of the CGRP receptor. Compound 20 was found to be among the most potent (IC(50)=17pM). It was shown to retain excellent aqueous solubility (>50mg/mL, pH 7) while dramatically improving solution stability as compared to our previously disclosed development candidate, BMS-694153 (1).
降钙素基因相关肽（CGRP）受体与偏头痛的发病机制有关。一类氨基甲酸酯衍生物已被鉴定为CGRP受体的强效抑制剂。发现化合物20是最有效的之一（IC(50)=17pM）。与我们之前公开的研发候选药物BMS-694153（1）相比，它显示出优异的水溶性（>50mg/mL，pH 7），同时显著提高了溶液稳定性。
