56844-41-8Relevant academic research and scientific papers
6-Cinnamoyl-4-arylaminothienopyrimidines as highly potent cytotoxic agents: Design, synthesis and structure-activity relationship studies
Aghcheli, Ayoub,Bakhshaiesh, Tayebeh Oghabi,Esmaeili, Rezvan,Foroumadi, Alireza,Hasanvand, Zaman,Khalaj, Ali,Moghimi, Setareh,Nazeri, Elahe,Salarinejad, Somayeh,Toolabi, Mahsa
, (2019/11/03)
In this paper, we described the synthesis and cytotoxic activities of two new series of thieno[2,3-d]pyrimidine and thieno[3,2-d] pyrimidine derivatives. Most of the synthesized compounds had significant antiproliferative activities against PC3, MDA-MB-23
Irreversible inhibitors of the epidermal growth factor receptor: Thienopyrimidine core with α,β-unsaturated amide side chain
Yang, Xiu L.,Wang, Tian C.,Lin, Sen,Fan, Hou X.
, p. 552 - 558 (2014/08/18)
Overexpression of epidermal growth factor receptor (EGFR) tyrosine kinases has been found in a variety of cancers such as breast, ovarian, colon, and non-small-cell lung cancers, which is associated with poor prognosis in patients. In an effort to find effective irreversible inhibitors of the EGFR tyrosine kinase family (mainly HER2), two series of HER2 tyrosine kinase inhibitors with thieno[3,2-d]pyridine and thieno[2,3-d]pyridine as central part and with a basic α,β-unsaturated amide side chain were developed. The α,β-unsaturated amide side chain (the Michael acceptor) at the 6-position, which forms a covalent bond to Cys773 located in the ATP binding pocket of the EGFR enzyme, is a major factor in the generation of irreversible inhibition. In our study, thienopyrimidine instead of quinazoline was used as the central structure, and different substituents were introduced at the 4-position to investigate the structure-activity relationships. The thieno[2,3-d]pyrimidine derivatives 16a-d showed potent HER2 enzyme inhibition and anti-proliferative activity against SK-BR-3 cells. Especially, (E)-N-(4-((3-chloro-4-(pyridin-2-ylmethoxy)phenyl)amino)thieno[2,3-d] pyrimidin-6-yl)-4-(dimethylamino)but-2-enamide 16d was identified as a potential irreversible HER2 inhibitor. Both its catalytic enzyme activity profile and its cellular efficacy were found to be superior to those of the marketed drug lapatinib.
Design, synthesis and biological evaluation of novel 6-alkenylamides substituted of 4-anilinothieno[2,3-d]pyrimidines as irreversible epidermal growth factor receptor inhibitors
Ji, Xun,Peng, Ting,Zhang, Xu,Li, Jian,Yang, Wei,Tong, Linjiang,Qu, Rong,Jiang, Hualiang,Ding, Jian,Xie, Hua,Liu, Hong
, p. 2366 - 2378 (2014/04/17)
A novel series of 6-alkenylamides of 4-anilinothieno[2,3-d]pyrimidine derivatives was designed, synthesized and evaluated as irreversible inhibitors of the epidermal growth factor receptor (EGFR). Most of the compounds exhibited good potency against EGFR wild type (EGFR wt) and EGFR T790M/L858R. Among these, the half-maximal inhibitory concentration (IC50) values of 17 compounds against EGFR wt were less than 0.020 μM, and those of 12 compounds were less than 0.010 μM. The IC50 values of 10 compounds against EGFR T790M/L858R were less than 0.005 μM. Compounds 8l, 9n, 9o, 9q and 9v almost completely blocked the phosphorylation of EGFR in the A431 cell line at 1 μM. Compounds 8l, 9n, 9o, 9q and 9v blocked the autophosphorylation of EGFR in NCI-H1975 cells at high concentration (1 μM), and compound 8l was confirmed to be an irreversible inhibitor through the dilution method.
Design, synthesis and biological evaluation of 4-anilinothieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as novel histone deacetylase inhibitors
Yang, Wei,Li, Lixuan,Ji, Xun,Wu, Xiaowei,Su, Mingbo,Sheng, Li,Zang, Yi,Li, Jia,Liu, Hong
, p. 6146 - 6155 (2015/02/02)
A series of 4-anilinothieno[2,3-d]pyrimidine-based hydroxamic acid derivatives as novel HDACs inhibitors were designed, synthesized and evaluated. Most of these compounds displayed good to excellent inhibitory activities against HDAC1, 3, 6. The IC50 values of compound 10r against HDAC1, HDAC3, HDAC6 was 1.14 ± 0.03 nM, 3.56 ± 0.08 nM, 11.43 ± 0.12 nM. Compound 10r noticeably up-regulated the level of histone H3 acetylation compared to the SAHA. Most of the compounds showed the strong anti-proliferative activity against human cancer cell lines including RMPI8226 and HCT-116. The IC50 values of Compounds 10r and 10t against RPMI8226 was 2.39 ± 0.20 μM, 1.41 ± 0.44 μM, respectively, and the HCT-116 was sensitive to the compounds 10h, 10m, 10r, 10w with the IC50 values 1.9 μM.
