145448-33-5Relevant academic research and scientific papers
Design, synthesis and anticancer evaluation of thieno[2,3-d]pyrimidine derivatives as dual EGFR/HER2 inhibitors and apoptosis inducers
Elmetwally, Souad A.,Saied, Khaled F.,Eissa, Ibrahim H.,Elkaeed, Eslam B.
, (2019/05/06)
Deregulation of many kinases is directly linked to cancer development and the tyrosine kinase family is one of the most important targets in current cancer therapy regimens. In this study, we have designed and synthesized a series of thieno[2,3-d]pyrimidine derivatives as an EGFR and HER2 tyrosine kinase inhibitors. All the synthesized compounds were evaluated in vitro for their inhibitory activities against EGFRWT; and the most active compounds that showed promising IC50 values against EGFRWT were tested in vitro for their inhibitory activities against mutant EGFRT790M and HER2 kinases. Moreover, the antitumor activities of these compounds were tested against four cancer cell lines (HepG2, HCT-116, MCF-7 and A431). Compounds 13g, 13h and 13k exhibited the highest activities against the examined cell lines with IC50 values ranging from 7.592 ± 0.32 to 16.006 ± 0.58 μM comparable to that of erlotinib (IC50 ranging from 4.99 ± 0.09 to 13.914 ± 0.36 μM). Furthermore, the most potent antitumor agent (13k) was selected for further studies to determine its effect on the cell cycle progression and apoptosis in MCF-7 cell line. The results indicated that this compound arrests G2/M phase of the cell cycle and it is a good apoptotic agent. Finally, molecular docking studies showed a good binding pattern of the synthesized compounds with the prospective target, EGFRWT and EGFRT790M.
A Microwave-Enhanced Synthesis and Biological Evaluation of N-Aryl-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amines
Han, Qing,Yin, Zijian,Sui, Jingjiao,Wang, Qingming,Sun, Yaquan
, p. 1483 - 1497 (2019/08/26)
A series of N-aryl-5,6,7,8-tetra-hydrobenzo[4,5]thieno[2,3-d]pyrimidin-4-amines were synthesized in moderate to good yield by using a microwave-enhanced conditions. The selected compounds were evaluated for their cytotoxic effects (IC50 values) on human pulmonary carcinoma (A549), murine BALB/c spontaneous colon adenocarcinoma (CT26) and human hepatocellular liver carcinoma (HepG2) cell lines in vitro. Amongst these compounds, one compound was found to have the better cytotoxic activity with reference to the standard Erlotinib hydrochloride (TarcevaTM) against A549 (IC50 = 16.06 ± 0.09 μM) and HepG2 (IC50 = 15.01 ± 0.31 μM) cell lines. Especially, two compounds showed best cytotoxic effects against CT26 (IC50 = 11.38 ± 0.44 μM) and HepG2 (IC50 = 8.51 ± 0.52 μM) cell lines, respectively. The preliminary structure-activity relationships were disclosed and the thieno[2,3-d]pyrimidine skeleton could be exploited to potential antitumor agents in the future.
Identification of 5,6-substituted 4-aminothieno[2,3-d]pyrimidines as LIMK1 inhibitors
Sleebs, Brad E.,Nikolakopoulos, George,Street, Ian P.,Falk, Hendrik,Baell, Jonathan B.
supporting information; experimental part, p. 5992 - 5994 (2011/10/18)
4-Aminobenzothieno[3,2-d]pyrimidines were previously identified in a high throughput screening campaign as LIMK1 inhibitors. Scaffold reversal led to the identification of a series of simple 5,6-substituted 4-aminothieno[2,3-d] pyrimidines with low micromolar inhibition of LIMK1.
Synthesis and study of antiproliferative activity of novel thienopyrimidines on glioblastoma cells
Pédeboscq, Stéphane,Gravier, Denis,Casadebaig, Fran?oise,Hou, Geneviève,Gissot, Arnaud,De Giorgi, Francesca,Ichas, Fran?ois,Cambar, Jean,Pometan, Jean-Paul
experimental part, p. 2473 - 2479 (2010/07/08)
The receptor tyrosine kinases (for example EGFR, PDGFR, VEGFR) are a transmembrane protein family which plays a crucial role in tumor growth, survival, metastasis dissemination and angiogenesis. During the past 10 years, many tyrosine kinase inhibitors (T
Microwave-based synthesis of novel thienopyrimidine bioisosteres of gefitinib
Phoujdar, Manisha S.,Kathiravan, Muthu K.,Bariwal, Jitender B.,Shah, Anamik K.,Jain, Kishor S.
, p. 1269 - 1273 (2008/09/18)
A series of novel 2-unsubstituted 4-(substituted)anilinothieno[2,3-d]pyrimidines is synthesized through the chlorination of the corresponding 2-unsubstituted-thieno[2,3-d]-pyrimidin-4-ones, followed by the nucleophilic displacement of the 4-Cl group of 9, with a variety of anilines. All four steps of this synthesis involve microwave irradiation (MWI) and the entire synthesis requires only 2 h.
