5848-05-5Relevant articles and documents
Synthesis and biological evaluation of novel pyrazolo[1,5-a]pyrimidines: Discovery of a selective inhibitor of JAK1 JH2 pseudokinase and VPS34
Singleton, Justin D.,Dass, Reuben,Neubert, Nathaniel R.,Smith, Rachel M.,Webber, Zak,Hansen, Marc D.H.,Peterson, Matt A.
supporting information, (2019/12/24)
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 commercially-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 4.3 μM, with the 3-(4-(trifluoromethyl)phenyl)-6-[4-(2-(piperidin-1-yl)ethoxy]phenyl analogue (34e) and the 3-(2-fluorophenyl)-6-[4-(2-(4-methylpiperizin-1-yl)ethoxy]phenyl analogue (35a) being two to three fold more active than Compound C (Dorsomorphin) in A2780 and MCF7 assays, respectively. Importantly, a monosubstituted 3-(benzothiazol-2-yl) derivative (13) was equipotent with the more synthetically challenging 3,6-disubstituted derivatives (34a–e and 35a–e), 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 ± 0.055 μM and 0.410 ± 0.20 μM for JAK1 JH2 pseudokinase and VPS34, respectively).
Discovery and characterization of a novel 7-aminopyrazolo[1,5-a]pyrimidine analog as a potent hepatitis C virus inhibitor
Hwang, Jong Yeon,Windisch, Marc Peter,Jo, Suyeon,Kim, Keumhyun,Kong, Sunju,Kim, Hyoung Cheul,Kim, Soohyun,Kim, Heeyoung,Lee, Myung Eun,Kim, Youngmi,Choi, Jihyun,Park, Dong-Sik,Park, Eunjung,Kwon, Jeongjin,Nam, Jiyoun,Ahn, Sujin,Cechetto, Jonathan,Kim, Junwon,Liuzzi, Michel,No, Zaesung,Lee, Jinhwa
, p. 7297 - 7301 (2013/02/23)
We describe a novel 7-aminopyrazolo[1,5-a]pyrimidine (7-APP) derivative as a potent hepatitis C virus (HCV) inhibitor. A series of 7-APPs was synthesized and evaluated for inhibitory activity against HCV in different cell culture systems. The synthesis and preliminary structure-activity relationship study of 7-APP are reported.