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. Online ahead of print.ABSTRACTThe 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.PMID:38065292 | DOI:10.1016/j.bmcl.2023.129575

Source: Bioorganic and Medicinal Chemistry Letters - December 8, 2023 Category: Chemistry Authors: Hideaki Kageji Takayuki Momose Yasuhito Nagamoto Noriko Togashi Isao Yasumatsu Yosuke Nishikawa Kawori Kihara Kumiko Hiramoto Megumi Minami Naomi Kasanuki Takeshi Isoyama Hiroyuki Naito Source Type: research