|
|||||
|
|
Synthesis and SAR development of novel mGluR1 antagonists for the treatment of chronic pain |
|
| Authors: | Stephanie Brumfield Peter Korakas Lisa S. Silverman Deen Tulshian Julius J. Matasi Li Qiang Chad E. Bennett Duane A. Burnett William J. Greenlee Chad E. Knutson Wen-Lian Wu T.K. Sasikumar Martin Domalski Rosalia Bertorelli Mariagrazia Grilli Gianluca Lozza Angelo Reggiani Cheng Li |
| Affiliation: | 1. Merck Research Laboratories, 2015 Galloping Hill Road, MS 2545, Kenilworth, NJ 07033-0539, USA;2. Merck Research Laboratories, San Raffaele Science Park, Via Olgettina, 58, 20132 Milan, Italy |
| Abstract: | High throughput screening identified the pyridothienopyrimidinone 1 as a ligand for the metabotropic glutamate receptor 1 (mGluR1 = 10 nM). Compound 1 has an excellent in vivo profile; however, it displays unfavorable pharmacokinetic issues and metabolic stability. Therefore, using 1 as a template, novel analogues (10i) were prepared. These analogues displayed improved oral exposure and activity in the Spinal Nerve Ligation (SNL) pain model. |
| Keywords: | |
| 本文献已被 ScienceDirect 等数据库收录！ | |