Discovery of VU6028418: A Highly Selective and Orally Bioavailable M4 Muscarinic Acetylcholine Receptor Antagonist was written by Spock, Matthew;Carter, Trever R.;Bollinger, Katrina A.;Han, Changho;Baker, Logan A.;Rodriguez, Alice L.;Peng, Li;Dickerson, Jonathan W.;Qi, Aidong;Rook, Jerri M.;O’Neill, Jordan C.;Watson, Katherine J.;Chang, Sichen;Bridges, Thomas M.;Engers, Julie L.;Engers, Darren W.;Niswender, Colleen M.;Conn, P. Jeffrey;Lindsley, Craig W.;Bender, Aaron M.. And the article was included in ACS Medicinal Chemistry Letters in 2021.Quality Control of 3,6-Dichloropyridazine This article mentions the following:
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 preclin. 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. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0Quality Control of 3,6-Dichloropyridazine).
3,6-Dichloropyridazine (cas: 141-30-0) belongs to pyridazine derivatives. The pyridazine structure is also found within the structure of several drugs such as cefozopran, cadralazine, minaprine, pipofezine, and hydralazine. Pyridazine can act as a hydrogen bond acceptor to improve the physicochemical properties of drug molecules by increasing their water solubility, and has a high affinity for complexing with targets due to its dipole moment.Quality Control of 3,6-Dichloropyridazine
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem