2. Academic Validation
  3. Synthesis, activity, and their relationships of 2,4-diaminonicotinamide derivatives as EGFR inhibitors targeting C797S mutation

Synthesis, activity, and their relationships of 2,4-diaminonicotinamide derivatives as EGFR inhibitors targeting C797S mutation

  • Bioorg Med Chem Lett. 2023 Dec 6:129575. doi: 10.1016/j.bmcl.2023.129575.
Hideaki Kageji 1,  Takayuki Momose 2,  Yasuhito Nagamoto 2,  Noriko Togashi 2,  Isao Yasumatsu 3,  Yosuke Nishikawa 3,  Kawori Kihara 4,  Kumiko Hiramoto 4,  Megumi Minami 4,  Naomi Kasanuki 4,  Takeshi Isoyama 2,  Hiroyuki Naito 2
Affiliations

Affiliations

  • 1 R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: [email protected].
  • 2 R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 3 Daiichi Sankyo RD Novare Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 4 Daiichi Sankyo RD Novare Co., Ltd., 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan.
PMID: 38065292 DOI: 10.1016/j.bmcl.2023.129575
Abstract

The C797S mutation is one of the major factors behind resistance to the third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors. Herein, we describe the discovery of the 2,4-diaminonicotinamide derivative 5j, which shows potent inhibitory activity against EGFR del19/T790M/C797S and L858R/T790M/C797S. We also report the structure-activity relationship of the 2,4-diaminonicotinamide derivatives and the co-crystal structure of 5j and EGFR del19/T790M/C797S.

Keywords

C797S; Drug discovery; EGFR.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-163094
    EGFR Inhibitor