691369-18-3Relevant articles and documents
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 (2016/07/20)
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.
4-Arylamino-6-nitroquinazolines: Synthesis and their activities against neglected disease leishmaniasis
Saad, Syed Muhammad,Ghouri, Nida,Perveen, Shahnaz,Khan, Khalid Mohammed,Choudhary, M. Iqbal
, p. 13 - 20 (2015/12/05)
4-Arylamino-6-nitroquinazolines (2-25) were synthesized and evaluated for their leishmanicidal activities against Leishmania major promastigotes in vitro with IC50 values Combining double low line 1.87-61.48 μM. Among the twenty four synthetic derivatives, 4-[4′-(methylsulfanyl)phenyl]amino-6-nitroquinazoline (21), and 4-(2′-methoxyphenyl)amino-6-nitroquinazoline (8) showed excellent antileishmanial activities with IC50 values 1.87 ± 0.31 and 4.37 ± 0.02 μM, respectively, more active than the standard drug, pentamidine (IC50 Combining double low line 5.09 ± 0.09 μM). Compound 16 (IC50 Combining double low line 6.53 ± 0.21 μM) displayed an activity comparable to the standard. Compounds 15 (IC50 Combining double low line 9.04 ± 0.03 μM), 18 (IC50 Combining double low line 12.28 ± 0.18 μM), 14 (IC50 Combining double low line 19.87 ± 0.22 μM), and 5 (IC50 Combining double low line 24.03 ± 2.71 μM) also showed good activities.
Design, synthesis and biological evaluation of novel quinazoline-based anti-inflammatory agents acting as PDE4B inhibitors
Serya, Rabah Ahmed Taha,Abbas, Abeer Hussin,Ismail, Nasser Saad Mohamed,Esmat, Ahmed,El Ella, Dalal Abdelrahman Abou
, p. 102 - 116 (2015/02/19)
A novel series of quinzoline based compounds (IIIa-d, VIa-f, IXa-f) were designed, synthesized and screened for their inhibitory activity towards the PDE4B isoform. The in vivo anti-inflammatory effect of the titled compounds (IIIa-d, VIa-f, IXa-f) as well as their effect on the level of tumor necrosis factor (TNF-α) were evaluated. Among all of the synthesized compounds, IXb, IXd and IXf, exhibited good inhibitory activity against PDE4B enzyme with inhibition percentages of 42, 62 and 68%, respectively. Most of the tested compounds showed potent anti-inflammatory activity compared to indomethacin with a marked decrease in TNF-α level. The ulcerogenic effect of the tested compounds was also examined. The gastric mucosa of the tested animals remained intact after oral administration of the hit compounds. Additionally, docking study was used to explore the possible binding mode of the active compounds on the PDE4B enzyme as well as to illustrate the selectivity of the active hits on the PDE4B isoform.
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
experimental part, 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.
