Electric Literature of C6H3ClFNO2On May 12, 2022 ,《Conformational Constrained 4-(1-Sulfonyl-3-indol)yl-2-phenylaminopyrimidine Derivatives as New Fourth-Generation Epidermal Growth Factor Receptor Inhibitors Targeting T790M/C797S Mutations》 appeared in Journal of Medicinal Chemistry. The author of the article were Chen, Hao; Lai, Mengzhen; Zhang, Tao; Chen, Yuqing; Tong, Linjiang; Zhu, Sujie; Zhou, Yang; Ren, Xiaomei; Ding, Jian; Xie, Hua; Lu, Xiaoyun; Ding, Ke. The article conveys some information:
Tertiary C797S mutation of epidermal growth factor receptor (EGFR)-mediated resistance in non-small-cell-lung-cancer (NSCLC) patients is still an unmet clin. need. Several classes of ATP-competitive or allosteric EGFRT790M/C797S inhibitors and degraders have been developed, but none of them have received approval from the regulatory agencies. Herein, we report the structure-based design of conformational constrained 4-(1-ethylsufonyl-3-indolyl)-2-phenylaminopyrimidines as new EGFRT790M/C797S inhibitors by using a macrocyclization strategy. Representative compound 18j potently inhibited EGFR19del/T790M/C797S and EGFRL858R/T790M/C797S mutants with IC50 values of 15.8 and 23.6 nM and suppressed Ba/F3-EGFRL858R/T790M/C797S and Ba/F3-EGFR19del/T790M/C797S cells with IC50 values of 0.036 and 0.052 μM, resp., which is 10-20-fold more potent than brigatinib. 18j also potently inhibited the EGFR19del/T790M/C797S-mutated PC-9-OR NSCLC cell proliferation with an IC50 value of 0.644 μM but was less potent for parental Ba/F3 and A431 cells. This study provides a new lead compound for drug discovery to combat EGFRC797S-mediated resistance in NSCLC patients. In the part of experimental materials, we found many familiar compounds, such as 3-Chloro-4-fluoronitrobenzene(cas: 350-30-1Electric Literature of C6H3ClFNO2)
3-Chloro-4-fluoronitrobenzene(cas: 350-30-1) belongs to organochlorine compounds. The wide structural variety and divergent chemical properties of organochlorides lead to a broad range of names, applications, and properties.Electric Literature of C6H3ClFNO2 Organochlorine compounds have wide use in many applications, though some are of profound environmental concern, with TCDD being one of the most notorious.
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics