1290545-26-4Relevant academic research and scientific papers
Toward discovery of mutant EGFR inhibitors; Design, synthesis and in vitro biological evaluation of potent 4-arylamino-6-ureido and thioureido-quinazoline derivatives
Mowafy, Samar,Galanis,Doctor, Zainab M.,Paranal, Raymond M.,Lasheen, Deena S.,Farag, Nahla A.,J?nne, Pasi A.,Abouzid, Khaled A.M.
, p. 3501 - 3512 (2016)
A new series of 4-anilinoquinazolines with C-6 ureido and thioureido side chains and various substituents at the C-4 anilino moiety was designed, synthesized and evaluated as wild type (WT) and mutant EGFR inhibitors. Most of the compounds inhibited EGFR kinase wild type (EGFR WT) with IC50values in the low nanomolar range (50?=?1.76–2.38?μM) in these mutant lines and significant Her2 enzyme inhibition (IC50?=?19.2–40.6?nM) compared to lapatinib (60.1?nM). The Binding mode of compounds 6d, 6f, 7a, 7b and 8b were demonstrated. Furthermore, growth inhibition against gefitinib insensitive cell lines PC9-GR4 (Del19/T790M) were tested, compounds 6f and 7e showed about eight and three folds respectively greater potency than gefitinib. Our structure–activity relationships (SAR) studies suggested that presence of ethyl piperidino urea/thiourea at 6-position and bulky group of (3-chloro-4-(3-fluorobenzyloxy)phenyl)amino at 4-position of quinazoline may serve as promising scaffold for developing inhibitors against wild type and mutant EGFR.
Design, synthesis and antitumor evaluation of phenyl N-mustard-quinazoline conjugates
Marvania, Bhavin,Lee, Pei-Chih,Chaniyara, Ravi,Dong, Huajin,Suman, Sharda,Kakadiya, Rajesh,Chou, Ting-Chao,Lee, Te-Chang,Shah, Anamik,Su, Tsann-Long
, p. 1987 - 1998 (2011/04/25)
A series of N-mustard-quinazoline conjugates was synthesized and subjected to antitumor studies. The N-mustard pharmacophore was attached at the C-6 of the 4-anilinoquinazolines via a urea linker. To study the structure-activity relationships of these conjugates, various substituents were introduced to the C-4 anilino moiety. The preliminary antitumor studies revealed that these agents exhibited significant antitumor activity in inhibiting various human tumor cell growths in vitro. Compounds 21b, 21g, and 21h were selected for further antitumor activity evaluation against human breast carcinoma MX-1 and prostate PC-3 xenograft in animal model. These agents showed 54-75% tumor suppression with low toxicity (5-7% body-weight changes). We also demonstrate that the newly synthesized compounds are able to induce DNA cross-linking through alkaline agarose gel shift assay and inhibited cell cycle arrest at G2/M phase.
