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  3. Discovery of novel [1,2,4]triazolo[4,3-a]quinoxaline aminophenyl derivatives as BET inhibitors for cancer treatment

Discovery of novel [1,2,4]triazolo[4,3-a]quinoxaline aminophenyl derivatives as BET inhibitors for cancer treatment

  • Bioorg Med Chem Lett. 2017 Oct 15;27(20):4606-4613. doi: 10.1016/j.bmcl.2017.09.025.
Imran Ali 1,  Jooyun Lee 2,  Areum Go 1,  Gildon Choi 3,  Kwangho Lee 4
Affiliations

Affiliations

  • 1 Bio-Organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 34114, Republic of Korea; Medicinal Chemistry & Pharmacology, Korea University of Science & Technology, Daejeon 34113, Republic of Korea.
  • 2 Bio-Organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 34114, Republic of Korea.
  • 3 Bio-Organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 34114, Republic of Korea; Medicinal Chemistry & Pharmacology, Korea University of Science & Technology, Daejeon 34113, Republic of Korea. Electronic address: gchoi@krict.re.kr.
  • 4 Bio-Organic Science Division, Korea Research Institute of Chemical Technology, PO Box 107, Daejeon 34114, Republic of Korea; Medicinal Chemistry & Pharmacology, Korea University of Science & Technology, Daejeon 34113, Republic of Korea. Electronic address: kwangho@krict.re.kr.
PMID: 28939121 DOI: 10.1016/j.bmcl.2017.09.025
Abstract

Bromodomain and extra-terminal (BET) proteins, a class of epigenetic reader domains has emerged as a promising new target class for small molecule drug discovery for the treatment of Cancer, inflammatory, and autoimmune diseases. Starting from in silico screening campaign, herein we report the discovery of novel BET inhibitors based on [1,2,4]triazolo[4,3-a]quinoxaline scaffold and their biological evaluation. The hit compound was optimized using the medicinal chemistry approach to the lead compound with excellent inhibitory activities against BRD4 in the binding assay. The substantial antiproliferative activities in human Cancer cell lines, promising drug-like properties, and the selectivity for the BET family make the lead compound (13) as a novel BRD4 Inhibitor motif for anti-cancer drug discovery.

Keywords

BET; BRD4; Bromodomains; Cancer; Epigenetic readers; Triazoloquinoxaline; [1,2,4]Triazolo[4,3-a]quinoxaline.

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