The discovery of potent, selective, and orally bioavailable hNK1 antagonists derived from pyrrolidine |
| |
| Authors: | Lin Peter Chang Lehua Devita Robert J Young Jonathan R Eid Ronsar Tong Xinchun Zheng Song Ball Richard G Tsou Nancy N Chicchi Gary G Kurtz Marc M Tsao Kwei-Lan C Wheeldon Alan Carlson Emma J Eng Waisi Burns H Donald Hargreaves Richard J Mills Sander G |
| |
| Institution: | Department of Medicinal Chemistry, Merck & Co. Inc., PO Box 2000, Rahway, NJ 07065-0900, USA. peter_lin@merck.com |
| |
| Abstract: | SAR studies on amides, ureas, and vinylogous amides derived from pyrrolidine led to the discovery of several potent hNK(1) antagonists. One particular vinylogous amide (45b) had excellent potency, selectivity, pharmacokinetic profile, and functional activity in vivo. An in vivo rhesus macaque brain receptor occupancy PET study for compound 45b revealed an estimated Occ(90) approximately 300 ng/ml. |
| |
| Keywords: | |
| 本文献已被 ScienceDirect PubMed 等数据库收录！ |
|
