2. Academic Validation
  3. Design, synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl) pyrimidine analogues as selective and potent Raf inhibitors

Design, synthesis and biological evaluation of benzyl 2-(1H-imidazole-1-yl) pyrimidine analogues as selective and potent Raf inhibitors

  • Bioorg Med Chem Lett. 2014 Aug 1;24(15):3600-4. doi: 10.1016/j.bmcl.2014.05.030.
Minjung Kim 1,  Junghun Lee 1,  Kyungjin Jung 1,  Hyangmi Kim 1,  Waqar Aman 1,  Jae-Sang Ryu 2,  Jung-Mi Hah 3
Affiliations

Affiliations

  • 1 Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea.
  • 2 College of Pharmacy & Graduate School of Pharmaceutical Sciences, Global Top 5 Research Program, Ewha Womans University, 11-1 Daehyun-Dong, Seodaemun-Gu, Seoul 120-750, Republic of Korea.
  • 3 Department of Pharmacy, College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, Kyeonggi-do 426-791, Republic of Korea. Electronic address: jhah@hanyang.ac.kr.
PMID: 24878193 DOI: 10.1016/j.bmcl.2014.05.030
Abstract

The synthesis of a novel series of (4-aminobenzyl/benzoyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives 9, 10, 18, 19 and their in vitro antiproliferative activities against the A375P human melanoma cell line and the U937 human leukemic monocyte lymphoma cell line are described. Potent antiproliferative effects were found from 9l, 9s and 10c; 10c was found to be a highly potent and selective BRaf V600E and CRAF inhibitor (IC50=38.3 nM and 8.79 nM).

Keywords

(4-Aminobenzyl)-1H-imidazol-1-yl pyrimidin-2-yl derivatives; Antiproliferative activity; BRAF V600E; CRAF; Melanoma; Selectivity.

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