7btv › Citations

Discovery of novel histone lysine methyltransferase G9a/GLP (EHMT2/1) inhibitors: Design, synthesis, and structure-activity relationships of 2,4-diamino-6-methylpyrimidines.

Katayama K, Ishii K, Tsuda E, Yotsumoto K, Hiramoto K, Suzuki M, Yasumatsu I, Igarashi W, Torihata M, Ishiyama T, Katagiri T
Bioorg Med Chem Lett 30 127475 (2020)
Cited: 6 times
EuropePMC logo PMID: 32781218

Abstract

The discovery and optimization of a novel series of G9a/GLP (EHMT2/1) inhibitors are described. Starting from known G9a/GLP inhibitor 5, efforts to explore the structure-activity relationship and optimize drug properties led to a novel compound 13, the side chain of which was converted to tetrahydroazepine. Compound 13 showed increased G9a/GLP inhibitory activity compared with compound 5. In addition, compound 13 exhibited improved human ether-a-go-go related gene (hERG) inhibitory activity over compound 5 and also improved pharmacokinetic profile in mice (oral bioavailability: 17 to 40%). Finally, the co-crystal structure of G9a in complex with compound 13 provides the basis for the further development of tetrahydroazepine-based G9a/GLP inhibitors.

Reviews citing this publication (2)

  1. Lysine methyltransferase inhibitors: where we are now. Feoli A, Viviano M, Cipriano A, Milite C, Castellano S, Sbardella G. RSC Chem Biol 3 359-406 (2022)
  2. Quinazoline Based HDAC Dual Inhibitors as Potential Anti-Cancer Agents. Dhuguru J, Ghoneim OA. Molecules 27 2294 (2022)

Articles citing this publication (4)



Quick links