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Author:

Wang, Yan (Wang, Yan.) | Liu, Wen-Jian (Liu, Wen-Jian.) | Yin, Lei (Yin, Lei.) | Li, Heng (Li, Heng.) | Chen, Zhen-Hua (Chen, Zhen-Hua.) | Zhu, Dian-Xi (Zhu, Dian-Xi.) | Song, Xiu-Qing (Song, Xiu-Qing.) | Cheng, Zhen-Zhen (Cheng, Zhen-Zhen.) | Song, Peng (Song, Peng.) | Wang, Zhan (Wang, Zhan.) (Scholars:王湛) | Li, Zhi-Gang (Li, Zhi-Gang.)

Indexed by:

Scopus SCIE PubMed

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-1H-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). Compound 10d, 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, compound 10d could be a promising candidate and a good starting point as anticancer drugs. (C) 2018 Elsevier Ltd. All rights reserved.

Keyword:

CDK1 Potent Anticancer Abemaciclib CDK4/6 inhibitors Selective

Author Community:

  • [ 1 ] [Wang, Yan]Beijing Univ Technol, Dept Chem & Chem Engn, Beijing Key Lab Green Catalysis & Separat, Beijing 100124, Peoples R China
  • [ 2 ] [Song, Xiu-Qing]Beijing Univ Technol, Dept Chem & Chem Engn, Beijing Key Lab Green Catalysis & Separat, Beijing 100124, Peoples R China
  • [ 3 ] [Song, Peng]Beijing Univ Technol, Dept Chem & Chem Engn, Beijing Key Lab Green Catalysis & Separat, Beijing 100124, Peoples R China
  • [ 4 ] [Wang, Zhan]Beijing Univ Technol, Dept Chem & Chem Engn, Beijing Key Lab Green Catalysis & Separat, Beijing 100124, Peoples R China
  • [ 5 ] [Wang, Yan]Gan & Lee Pharmaceut R&D, 8 Jingsheng North 3rd St, Beijing 101102, Peoples R China
  • [ 6 ] [Liu, Wen-Jian]Gan & Lee Pharmaceut R&D, 8 Jingsheng North 3rd St, Beijing 101102, Peoples R China
  • [ 7 ] [Yin, Lei]Gan & Lee Pharmaceut R&D, 8 Jingsheng North 3rd St, Beijing 101102, Peoples R China
  • [ 8 ] [Li, Heng]Gan & Lee Pharmaceut R&D, 8 Jingsheng North 3rd St, Beijing 101102, Peoples R China
  • [ 9 ] [Chen, Zhen-Hua]Gan & Lee Pharmaceut R&D, 8 Jingsheng North 3rd St, Beijing 101102, Peoples R China
  • [ 10 ] [Zhu, Dian-Xi]Gan & Lee Pharmaceut R&D, 8 Jingsheng North 3rd St, Beijing 101102, Peoples R China
  • [ 11 ] [Cheng, Zhen-Zhen]Gan & Lee Pharmaceut R&D, 8 Jingsheng North 3rd St, Beijing 101102, Peoples R China
  • [ 12 ] [Li, Zhi-Gang]Beijing Handian Pharmaceut Co Ltd, Kuntai Int Bldg, Beijing 100020, Peoples R China

Reprint Author's Address:

  • 王湛

    [Wang, Zhan]Beijing Univ Technol, Dept Chem & Chem Engn, Beijing Key Lab Green Catalysis & Separat, Beijing 100124, Peoples R China;;[Li, Zhi-Gang]Beijing Handian Pharmaceut Co Ltd, Kuntai Int Bldg, Beijing 100020, Peoples R China

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Source :

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

ISSN: 0960-894X

Year: 2018

Issue: 5

Volume: 28

Page: 974-978

2 . 7 0 0

JCR@2022

ESI Discipline: CHEMISTRY;

ESI HC Threshold:192

JCR Journal Grade:3

Cited Count:

WoS CC Cited Count: 24

SCOPUS Cited Count: 28

ESI Highly Cited Papers on the List: 0 Unfold All

WanFang Cited Count:

Chinese Cited Count:

30 Days PV: 4

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