Synthesis and biological evaluation of novel pyrazolo[1,5-a]pyrimidines: Discovery of a selective inhibitor of JAK1 JH2 pseudokinase and VPS34 was written by Singleton, Justin D.;Dass, Reuben;Neubert, Nathaniel R.;Smith, Rachel M.;Webber, Zak;Hansen, Marc D. H.;Peterson, Matt A.. And the article was included in Bioorganic & Medicinal Chemistry Letters in 2020.COA of Formula: C8H5Cl2N This article mentions the following:
A series of novel 3,6-di-substituted or 3-substituted pyrazolo[1,5-a]pyrimidines were prepared via a microwave-assisted approach that generated a broad array of derivatives in good yields (20-93%, ave. = 59%). The straightforward synthesis involved sequential treatment of com.-available acetonitrile derivatives with DMF-dimethylacetal (120°C, 20 min), followed by treatment with NH2NH2·HBr (120°C, 20 min), and 1,1,3,3-tetramethoxypropane or 2-aryl-substituted malondialdehdyes (120°C, 20 min). Compounds were screened for antimitotic activities against MCF7 breast cancer and/or A2780 ovarian cancer cell lines in vitro. The most active compounds exhibited EC50 values ranging from 0.5 to 4.3μM, with the 3-(4-(trifluoromethyl)phenyl)-6-[4-(2-(piperidin-1-yl)ethoxy)]phenyl analog and the 3-(2-fluorophenyl)-6-[4-(2-(4-methylpiperizin-1-yl)ethoxy)]phenyl analog being two to three fold more active than Compound C (Dorsomorphin) in A2780 and MCF7 assays, resp. Importantly, a monosubstituted 3-(benzothiazol-2-yl) derivative was equipotent with the more synthetically challenging 3,6-disubstituted derivatives, and exhibited a promising and unique selectivity profile when screened against a panel consisting of 403 protein kinases (Kinomescan selectivity score = 0.005, Kd = 0.55 ± 0.055μM and 0.410 ± 0.20μM for JAK1 JH2 pseudokinase and VPS34, resp.). In the experiment, the researchers used many compounds, for example, 2-(2,3-Dichlorophenyl)acetonitrile (cas: 3218-45-9COA of Formula: C8H5Cl2N).
2-(2,3-Dichlorophenyl)acetonitrile (cas: 3218-45-9) belongs to nitriles. Nitrile function is a very important functional group because it can be manipulated to other functional groups such as carboxylic acid by hydrolysis or amine by reduction, respectively. In addition, Nitriles can react with alkynes, which leads to an increase in carbon chain length (carbocyanation).COA of Formula: C8H5Cl2N
Referemce:
Nitrile – Wikipedia,
Nitriles – Chemistry LibreTexts