Discovery of VU6028418: A Highly Selective and Orally Bioavailable M<sub>4</sub> Muscarinic Acetylcholine Receptor Antagonist.

Basic Information

ID: ALA4837245

Journal: ACS Med Chem Lett

Title: Discovery of VU6028418: A Highly Selective and Orally Bioavailable M₄ Muscarinic Acetylcholine Receptor Antagonist.

Authors: Spock M, Carter TR, Bollinger KA, Han C, Baker LA, Rodriguez AL, Peng L, Dickerson JW, Qi A, Rook JM, O'Neill JC, Watson KJ, Chang S, Bridges TM, Engers JL, Engers DW, Niswender CM, Conn PJ, Lindsley CW, Bender AM.

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.

CiteXplore: 34413964

DOI: 10.1021/acsmedchemlett.1c00363

Patent ID: ┄

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