Pharmacological Evaluation of Novel Bioisosteres of an Adamantanyl Benzamide P2X7 Receptor Antagonist was written by Wilkinson, Shane M.;Barron, Melissa L.;O’Brien-Brown, James;Janssen, Bieneke;Stokes, Leanne;Werry, Eryn L.;Chishty, Mansoor;Skarratt, Kristen K.;Ong, Jennifer A.;Hibbs, David E.;Vugts, Danielle J.;Fuller, Stephen;Windhorst, Albert D.;Kassiou, Michael. And the article was included in ACS Chemical Neuroscience in 2017.COA of Formula: C4H2Cl2N2 This article mentions the following:
Adamantanyl benzamide 1 was identified as a potent P2X7R antagonist but failed to progress further due to poor metabolic stability. We describe the synthesis and SAR of a series of bioisosteres of benzamide 1 to explore improvements in the pharmacol. properties of this lead. Initial efforts investigated a series of heteroaromatic bioisosteres, which demonstrated improved physicochem. properties but reduced P2X7R antagonism. Installation of bioisosteric fluorine on the adamantane bridgeheads was well tolerated and led to a series of bioisosteres with improved physicochem. properties and metabolic stability. Trifluorinated benzamide 34 demonstrated optimal physicochem. parameters, superior metabolic stability (ten times longer than lead benzamide 1), and an improved physicokinetic profile and proved effective in the presence of several known P2X7R polymorphisms. In the experiment, the researchers used many compounds, for example, 3,6-Dichloropyridazine (cas: 141-30-0COA of Formula: C4H2Cl2N2).
3,6-Dichloropyridazine (cas: 141-30-0) belongs to pyridazine derivatives. Pyridazine and phthalazine have quite different spectroscopic properties compared with their isomers, pyrazine and quinoxaline. 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.COA of Formula: C4H2Cl2N2
Referemce:
Pyridazine – Wikipedia,
Pyridazine | C4H4N2 – PubChem