Design and synthesis of 4-(2, 3-dihydro-1H-benzo[d]pyrrolo[1, 2-a]imidazol-7-yl)-N-(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine as a highly potent and selective cyclin-dependent kinases 4 and 6 inhibitors and the discovery of structure-activity relationships. Issue 5 (1st March 2018)

• Record Type: Journal Article
• Authors: Wang, Yan; Liu, Wen-Jian; Yin, Lei; Li, Heng; Chen, Zhen-Hua; Zhu, Dian-Xi; Song, Xiu-Qing; Cheng, Zhen-Zhen; Song, Peng; Wang, Zhan; Li, Zhi-Gang
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 28:Issue 5(2018)
• Page Start: 974
• Page End: 978
• Publication Date: 2018-03-01
• Subjects: CDK4/6 inhibitors -- CDK1 -- Abemaciclib -- Potent -- Selective -- Anticancer; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2017.12.068
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Cyclin-dependent kinases 4/6 play an important role in regulation of cell cycle, and overexpress in a variety of cancers. Up to now, new CDK inhibitors still need to be developed due to its poor selectivity. Herein we report a novel series of 4-(2, 3-dihydro-1 H -benzo[ d ]pyrrolo[1, 2- a ]imidazole-7-yl)- N -(5-(piperazin-1-ylmethyl)pyridine-2-yl)pyrimidin-2-amine anologues as potent CDK 4/6 inhibitors based on LY2835219 (Abemaciclib). Compound10d, which exhibits approximate potency on CDK4/6 (IC50 = 7.4/0.9 nM), has both good pharmacokinetic characters and high selectivity on CDK1 compared with LY2835219. Overall, compound10d could be a promising candidate and a good starting point as anticancer drugs.