Synthesis and SAR of calcitonin gene-related peptide (CGRP) antagonists containing substituted aryl-piperazines and piperidines
作者:Rita L. Civiello、Xiaojun Han、Brett R. Beno、Prasad V. Chaturvedula、John J. Herbst、Cen Xu、Charles M. Conway、John E. Macor、Gene M. Dubowchik
DOI:10.1016/j.bmcl.2016.01.026
日期:2016.2
improved oral bioavailability, metabolic stability, and pharmacokinetic properties, lower molecular weight, structurally simpler piperidine and piperazine analogs of BMS-694153 were prepared. Several were found to have nM binding affinity in vitro. The synthesis and SAR of these substituted piperidine and piperazine CGRP antagonists are discussed.
降钙素基因相关肽(CGRP)是一种强力神经肽,与偏头痛的病理生理有关。在寻求具有改善的口服生物利用度,代谢稳定性和药代动力学性质的CGRP拮抗剂的过程中,制备了BMS-694153的较低分子量,结构更简单的哌啶和哌嗪类似物。发现一些在体外具有nM结合亲和力。讨论了这些取代的哌啶和哌嗪CGRP拮抗剂的合成和SAR。