[논문]Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1 H- pyrazole derivatives as a novel selective inhibitor scaffold of JNK3

Oh, Youri; Jang, Miyoung; Cho, Hyunwook; Yang, Songyi; Im, Daseul; Moon, Hyungwoo; Hah, Jung-Mi

doi:10.1080/14756366.2019.1705294

[해외논문] Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1 H- pyrazole derivatives as a novel selective inhibitor scaffold of JNK3 원문보기

Journal of enzyme inhibition and medicinal chemistry, v.35 no.1, 2020년, pp.372 - 376

Oh, Youri (College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , Korea) , Jang, Miyoung (College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , Korea) , Cho, Hyunwook (College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , Korea) , Yang, Songyi (College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , Korea) , Im, Daseul (College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , Korea) , Moon, Hyungwoo (College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , Korea) , Hah, Jung-Mi (College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University , Ansan , Korea)

Abstract ▼ AI-Helper

Abstract3-alkyl-5-aryl-1-pyrimidyl-1H-pyrazole derivatives were designed and synthesised as selective inhibitors of JNK3, a target for the treatment of neurodegenerative diseases. Following previous studies, we have designed JNK3 inhibitors to reduce the molecular weight and successfully identified a lead compound that exhibits equipotent activity towards JNK3. Kinase profiling results also showed high selectivity for JNK3 among 38 kinases. Among the derivatives, the IC50 value of 8a, (R)-2-(1-(2-((1-(cyclopropanecarbonyl)pyrrolidin-3-yl)amino)pyrimidin-4-yl)-5-(3,4-dichlorophenyl)-1H-pyrazol-3-yl)acetonitrile exhibited 227 nM, showing the highest inhibitory activity against JNK3.

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참고문헌 (21)

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[해외논문] Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1 H- pyrazole derivatives as a novel selective inhibitor scaffold of JNK3 원문보기

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[해외논문] Discovery of 3-alkyl-5-aryl-1-pyrimidyl-1 H- pyrazole derivatives as a novel selective inhibitor scaffold of JNK3 원문보기

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