| Autor: |
Sichen Chang, Jonathan W. Dickerson, Baker Logan A, Thomas M. Bridges, Craig W. Lindsley, Darren W. Engers, Aidong Qi, Jerri M. Rook, Aaron M. Bender, P. Jeffrey Conn, Katrina A. Bollinger, Colleen M. Niswender, Changho Han, Alice L. Rodriguez, Trever R Carter, Li Peng, Julie L. Engers, Jordan C. O’Neill, Matthew Spock, Katherine J. Watson |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
ACS Med Chem Lett |
| ISSN: |
1948-5875 |
| DOI: |
10.1021/acsmedchemlett.1c00363 |
| Popis: |
[Image: see text] Herein, we report the SAR leading to the discovery of VU6028418, a potent M(4) 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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