| Literature DB >> 34413964 |
Matthew Spock1, Trever R Carter1, Katrina A Bollinger1, Changho Han1, Logan A Baker1, Alice L Rodriguez1, Li Peng1, Jonathan W Dickerson1, Aidong Qi1, Jerri M Rook1, Jordan C O'Neill1, Katherine J Watson1, Sichen Chang1, Thomas M Bridges1, Julie L Engers1, Darren W Engers1, Colleen M Niswender1, P Jeffrey Conn1, Craig W Lindsley1, Aaron M Bender1.
Abstract
Herein, we report the SAR leading to the discovery of VU6028418, a potent M4 mAChR antagonist with high subtype-selectivity and attractive DMPK properties in vitro and in vivo across multiple species. VU6028418 was subsequently evaluated as a preclinical candidate for the treatment of dystonia and other movement disorders. During the characterization of VU6028418, a novel use of deuterium incorporation as a means to modulate CYP inhibition was also discovered.Entities:
Year: 2021 PMID： 34413964 PMCID： PMC8366002 DOI： 10.1021/acsmedchemlett.1c00363
Source DB: PubMed Journal: ACS Med Chem Lett ISSN： 1948-5875 Impact factor: 4.632