Oxadiazole Derivatives as Dual Orexin Receptor Antagonists: Synthesis, Structure-Activity Relationships, and Sleep-Promoting Properties in Rats was written by Brotschi, Christine;Roch, Catherine;Gatfield, John;Treiber, Alexander;Williams, Jodi T.;Sifferlen, Thierry;Heidmann, Bibia;Jenck, Francois;Bolli, Martin H.;Boss, Christoph. And the article was included in ChemMedChem in 2019.Name: 2-(Trifluoromethoxy)benzonitrile This article mentions the following:
The orexin system plays an important role in the regulation of wakefulness. Suvorexant, a dual orexin receptor antagonist (DORA) is approved for the treatment of primary insomnia. Herein, we outline our optimization efforts toward a novel DORA. We started our investigation with rac-[3-(5-chloro-benzoxazol-2-ylamino)piperidin-1-yl]-(5-methyl-2-[1,2,3]triazol-2-ylphenyl)methanone (3, I), a structural hybrid of suvorexant and a piperidine-containing DORA. During the optimization, we resolved liabilities such as chem. instability, CYP3A4 inhibition, and low brain penetration potential. Furthermore, structural modification of the piperidine scaffold was essential to improve potency at the orexin 2 receptor. This work led to the identification of (5-methoxy-4-methyl-2-[1,2,3]triazol-2-ylphenyl)-{(S)-2-[5-(2-trifluoromethoxyphenyl)-[1,2,4]oxadiazol-3-yl]pyrrolidin-1-yl}methanone (51, II), a potent, brain-penetrating DORA with in vivo efficacy similar to that of suvorexant in rats. In the experiment, the researchers used many compounds, for example, 2-(Trifluoromethoxy)benzonitrile (cas: 63968-85-4Name: 2-(Trifluoromethoxy)benzonitrile).
2-(Trifluoromethoxy)benzonitrile (cas: 63968-85-4) belongs to nitriles. Nitrile compounds can be prepared by the incorporation of a cyanide source through C–C bond formation or by dehydration of primary carboxamides. Some nitriles are manufactured by heating carboxylic acids with ammonia in the presence of catalysts. This process is used to make nitriles from natural fats and oils, the products being used as softening agents in synthetic rubbers, plastics, and textiles and for making amines.Name: 2-(Trifluoromethoxy)benzonitrile
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts