Discovery of novel phenoxybenzamide analogues as Raf/HDAC dual inhibitors

  • Bioorg Med Chem Lett. 2019 Jul 1;29(13):1605-1608. doi: 10.1016/j.bmcl.2019.04.047.
Aixin Geng  1 ,  Hao Cui  1 ,  Liyuan Zhang  1 ,  Xin Chen  2 ,  Hongmei Li  1 ,  Tao Lu  3 ,  Yong Zhu  4
Affiliations
  • 1. Department of Organic Chemistry, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China.
  • 2. Department of Organic Chemistry, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; Shanxi Key Laboratory of Natural Products & Chemical Biology, College of Science, Northwest A&F University, Yangling 712100, China.
  • 3. Laboratory of Molecular Design and Drug Discovery, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China; State Key Laboratory of Natural Medicines, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: [email protected].
  • 4. Department of Organic Chemistry, School of Science, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China. Electronic address: [email protected].
PMID: 31053508 DOI: 10.1016/j.bmcl.2019.04.047
Abstract

Histone deacetylase (HDAC) inhibitors as an important epigenetic therapeutic strategy affect signaling networks and act synergistically with kinase inhibitors for the treatment of Cancer. Herein we presented a series of novel phenoxybenzamide analogues with inhibition of Raf and HDAC. Among them, compound 10e showed potent antiproliferative activities against Hepg2 and MDA-MB-468 in cellular assays. This work may lay the foundation for developing novel dual Raf/HDAC inhibitors as potential Anticancer therapeutics.

Keywords
Antiproliferative activity; Dual inhibitor; HDAC; Phenoxybenzamide; Raf.