14346-24-8Relevant articles and documents
Structure based design, synthesis and evaluation of new thienopyrimidine derivatives as anti-bacterial agents
Malasala, Satyaveni,Polomoni, Anusha,Ahmad, Md. Naiyaz,Shukla, Manjulika,Kaul, Grace,Dasgupta, Arunav,Chopra, Sidharth,Nanduri, Srinivas
, (2021)
TrmD, tRNA-(N1G37) methyltransferase, a member of SpoU-TrmD (SPOUT) RNA methyltransferase family, is one of the key enzymes responsible for the growth of Staphylococcus aureus, Pseudomonas aeruginosa, Mycobacterium tuberculosis (Mtb) and Mycobacterium abscessus (Mab). A number of TrmD inhibitors including thienopyrimidines and fused thienopyrimidines are reported as potent anti-bacterial and anti-mycobacterial agents. In the current study, a library of ~200 structurally diverse thienopyrimidines were designed and subjected to preliminary in silico studies. 22 of the compounds were selected, synthesized and were evaluated for their inhibitory activities against a panel of pathogens consisting E. coli, S. aureus, K. pneuminiae, A. baumannii and P. aeruginosa and M. tuberculosis (ATCC 27294). Among the tested compounds, 13b, 18a-e were found to inhibit M. tuberculosis (ATCC 27294) with the MIC of 16-32 μg/mL. The compound 18f was found to be selective against S. aureus with the MIC of 4 μg/mL and moderate activity against M. tuberculosis. The selected compounds were further subjected to docking, 3D-QSAR and ADME/T studies to understand the mechanism of action and also their physico chemical profile.
Synthesis and anticancer activities of novel (tetrahydrobenzo [4,5] thieno [2,3-d] pyrimidine-4-yl)-pyrolidine-2-carboxylic acid derivatives
Pavase, Laxmikant S.,Mane, Dhananjay V.
, p. 2380 - 2391 (2016)
Cancer chemotherapy has been one of the major medical advances in the last few decades. The medications involved in treatment have a narrow therapeutic index, and often the responses produced are only just palliative as well as unpredictable. In contrast,
Thienopyrimidine sulphonamide hybrids: Design, synthesis, antiprotozoal activity and molecular docking studies
Leeza Zaidi, Saadia,Agarwal, Subhash M.,Chavalitshewinkoon-Petmitr, Porntip,Suksangpleng, Thidarat,Ahmad, Kamal,Avecilla, Fernando,Azam, Amir
, p. 90371 - 90383 (2016)
A series of hybrid compounds containing the thienopyrimidine scaffold as a DHFR inhibitor fused with a bioactive sulphonamide piperazine skeleton were synthesized and evaluated against the chloroquine and pyrimethamine resistant K1 strain of Plasmodium falciparum and the HM1:1MSS strain of Entamoeba histolytica, respectively. A few of the compounds showed better results than the standard drugs. The toxicity of the hybrids was measured on the Chinese hamster cell line. The majority of the compounds had low toxicity. The binding modes of the most potent antimalarial compounds (5, 6 and 8) were also investigated against PfDHFR using molecular docking and enzyme binding studies, whereby 5 and 6 were found to the most promising against PfDHFR. The present studies suggest that these hybrids might be possible antiprotozoal lead compounds worth further investigation.
Hybrids of thienopyrimidinones and thiouracils as anti-tubercular agents: SAR and docking studies
Pisal, Mahesh M.,Nawale, Laxman U.,Patil, Manoj D.,Bhansali, Sujit G.,Gajbhiye, Jayant M.,Sarkar, Dhiman,Chavan, Subhash P.,Borate, Hanumant B.
, p. 459 - 469 (2017)
A number of hybrid molecules containing thienopyrimidinones and thiouracil moieties were designed, synthesized and tested against Mycobacterium tuberculosis H37Ra wherein it was observed that the compounds 11–14 exhibited antitubercular activity in?vitro
A facile synthesis of some novel fused [1,2,4]triazolo[3,4-b][1,3,4] thiadiazol derivatives
Nagaraju, Kerru,Kotaiah, Yalagala,Sampath, Chinnam,Harikrishna, Nallapaneni,Rao, Chunduri Venkata
, p. 264 - 275 (2013)
A series of novel 3-[6-(4-substituted phenyl)-[1,2,4]triazolo[3,4-b][1,3,4] thiadiazol-3-ylmethyl]-5,6,7,8-tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H) -one derivatives (7a-7h) have been synthesized from 2-amino-4,5,6,7- tetrahydrobenzo[b]thiophene-3-carbonitrile (1) through a multi-step reaction sequence. The key intermediate (6) on condensation with various substituted aromatic carboxylic acids in the presence of phosphorus oxychloride afforded the series of title compounds (7a-7h). The structures of all newly synthesized compounds were established on the basis of their IR, 1H-NMR, 13C-NMR and liquid chromatography mass spectrometry spectral data.
Structure based design of selective SHP2 inhibitors by De novo design, synthesis and biological evaluation
Liu, Wen-Shan,Jin, Wen-Yan,Zhou, Liang,Lu, Xing-Hua,Li, Wei-Ya,Ma, Ying,Wang, Run-Ling
, p. 759 - 774 (2019)
SHP2 phosphatase, encoded by the PTPN11 gene, is a non-receptor PTP, which plays an important role in growth factor, cytokine, integrin, hormone signaling pathways, and regulates cellular responses, such as proliferation, differentiation, adhesion migrati
Design, Synthesis, and Biological Evaluation of 5,6,7,8-Tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines as Microtubule Targeting Agents
Doshi, Arpit,Gangjee, Aleem,Hamel, Ernest,Islam, Farhana,Mooberry, Susan L.,Quadery, Tasdique M.,Robles, Andrew J.,Zhang, Xin,Zhou, Xilin
, (2022/01/11)
A series of eleven 4-substituted 5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidines were designed and synthesized and their biological activities were evaluated. Synthesis involved the Gewald reaction to synthesize ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate ring, and SNAr reactions. Compound 4 was 1.6-and ~7-fold more potent than the lead compound 1 in cell proliferation and microtubule depolymerization assays, respectively. Compounds 4, 5 and 7 showed the most potent antiproliferative effects (IC50 values 50 values of 53–125 nM). Additionally, compounds 4–8, 10 and 12–13 circumvented Pgp and βIII-tubulin mediated drug resistance, mechanisms that diminish the clinical efficacy of paclitaxel (PTX). In the NCI-60 cell line panel, compound 4 exhibited an average GI50 of ~10 nM in the 40 most sensitive cell lines. Compound 4 demonstrated statistically significant antitumor effects in a murine MDA-MB-435 xenograft model.
Design, molecular docking and biological evaluation of fused thienopyrimidines and quinazoline
Kaliraj,Jeyalakshmi,Kathiravan,Madhavan,Devi, Arikketh
, p. 537 - 544 (2021/02/27)
The anticancer activity of the condensed pyrimidine and quinazoline moieties are pronounced with a different pathway. Thienopyrimidine is considered as ring equivalent bioisosteres of quinazolines and present in other heterocyclic compounds including thienopyrimidine. The present investigation focused on the synthesis of thienopyrimidine and quinazoline derivatives for their anticancer activity against the human oral squamous carcinoma-3 (HSC-3) cell line. The synthesized compound confirmed for their structural characteristics from spectral analysis and tested for anti-proliferative activity from MTT assay. The electron-withdrawing group in 4-chloro thienopyrimidines and amino ester derivate/facilitate the inhibition of cancer cells. Further probing by docking studies revealed that the compounds exhibit possible interactions with VEGF, FGFR and c-Met proteins, which are known to have a role in the pathogenesis of oral squamous cell carcinoma. Among the derivatives a moderate activity demonstrated by substituted 4-chloro-5,6,7,8-tetrahydrobenzo[4,5]thieno[2,3-d]-pyrimidine (4a) and ethyl 2-amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate (1a) derivatives. Lack of chirality and the presence of bulky substituents in few of the compounds were found to be the cause for lower potency.
