|
|||||
|
|
Orally bioavailable imidazoazepanes as calcitonin gene-related peptide (CGRP) receptor antagonists: discovery of MK-2918 |
|
| Authors: | Paone Daniel V Nguyen Diem N Shaw Anthony W Burgey Christopher S Potteiger Craig M Deng James Z Mosser Scott D Salvatore Christopher A Yu Sean Roller Shane Kane Stefanie A Selnick Harold G Vacca Joseph P Williams Theresa M |
| Affiliation: | a Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA b Department of Pain and Migraine Research, Merck Research Laboratories, West Point, PA 19486, USA c Department of Drug Metabolism, Merck Research Laboratories, West Point, PA 19486, USA |
| Abstract: | In our ongoing efforts to develop CGRP receptor antagonists for the treatment of migraine, we aimed to improve upon telecagepant by targeting a compound with a lower projected clinical dose. Imidazoazepanes were identified as potent caprolactam replacements and SAR of the imidazole yielded the tertiary methyl ether as an optimal substituent for potency and hERG selectivity. Combination with the azabenzoxazinone spiropiperidine ultimately led to preclinical candidate 30 (MK-2918). |
| Keywords: | CGRP Migraine Calcitonin gene-related peptide Telcagepant MK-2918 |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ | |