Design, synthesis and in vitro antitumor evaluation of novel diaryl urea derivatives bearing sulfonamide moiety  

作　　者：LUO Can TANG Ke LI Yan YIN DaLi CHEN XiaoGuang HUANG HaiHong 

机构地区：[1]Beijing Key Laboratory of Active Substance Discovery and Druggability Evaluation [2]Institute of Materia Medica,Peking Union Medical College & Chinese Academy of Medical Sciences

出　　处：《Science China Chemistry》2013年第11期1564-1572,共9页中国科学（化学英文版）

基　　金：financially supported by the National Science&Technology Major Project(2009ZX09301-003-9-1)

摘　　要：A novel series of diaryl urea derivatives bearing sulfonamide moiety have been designed and synthesized. Their in vitro antitumor effect against human cancer cell lines MX-1, A375, HepG2, Ketr3 and HT-29 was screened and evaluated by the standard MTT assay with sorafenib as the positive control. Some of the compounds showed significant inhibitory activity against multiple cell lines compared to sorafenib. In particular, 2,6-dimethyl-4-{6-[3-（4-chloro-3-（trifluoromethyl）phenyl）urealnaphthalen- 2-yllsulfonyl morpholine （10d） was found to be the most potent against A375, HepG2 and Ketr3 with ICs0 values of 0.65-0.97 μmol/L, which were 5-20-fold more potent than sorafenib. Compound 10d emerged as a valuable lead for further optimization.A novel series of diaryl urea derivatives bearing sulfonamide moiety have been designed and synthesized.Their in vitro antitumor effect against human cancer cell lines MX-1,A375,HepG2,Ketr3 and HT-29 was screened and evaluated by the standard MTT assay with sorafenib as the positive control.Some of the compounds showed significant inhibitory activity against multiple cell lines compared to sorafenib.In particular,2,6-dimethyl-4-{6-[3-(4-chloro-3-(trifluoromethyl)phenyl)urea]naphthalen-2-yl}sulfonyl morpholine(10d)was found to be the most potent against A375,HepG2 and Ketr3 with IC50values of 0.65–0.97mol/L,which were 5–20-fold more potent than sorafenib.Compound 10d emerged as a valuable lead for further optimization.

关 键 词：diaryl urea derivatives SULFONAMIDE SORAFENIB antitumor activity 

分 类 号：TQ460.1[化学工程—制药化工]