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 of some new pyrimidine selanyl derivatives
Alshahrani, Refaah A.,Gobouri, Adil A.,Alshanbari, Naif A.,Ahmed, Saleh A.,Abdel-Hafez, Shams H.
, p. 345 - 349 (2018)
The targeted synthesis of 2-(methylsulfanyl)-6-(furan-2-yl)-4(3H)-selenoxo -pyrimidine-5-carbonitrile failed due to the formation 1-methyl-2-methylsulfanyl-6-oxo -4-(furan-2-yl)-1,6-dihydropyrimidine-5-carbonitrile. A new series of 5,6,7,8-tetrahydro-1-benzo thieno[2,3-d]pyrimidine-4-yl substituted selanyl derivatives were prepared by the reaction of sodium diselenide with 4-chloro-5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine followed by the reaction with chloroacetic acid derivatives such as ethyl chloroacetate, chloroacetamide or chloroacetonitrile. Hydrazinolysis of ethyl (5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidine- 4-ylselanyl)acetate with hydrazine hydrate gave the corresponding hydrazino derivative. The latter reacted with ethyl acetoacetate, acetylacetone, diethyl malonate, ethoxymethylenemalononitrile or ethyl 2-cyano-3-ethoxyacetate to afford 5-methyl-2-[2-(5,6,7,8-tetrahydro-1-benzothieno [2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydropyrazol-3-one, 1-(3,5-dimethylpyrazol-1-yl)-2- (5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-ylselanyl)ethanone, 1-[2-(5,6,7,8-tetrahydro -1-benzothieno[2,3-d]pyrimidine-4-ylselanyl)acetyl]-2,4-dihydropyrazolidine-3,5-dione and 5-Amino-1-[2-(5,6,7,8-tetrahydro-1-benzothieno[2,3-d]pyrimidin-4-ylselanyl)acetyl]-1H-pyrazol -4-yl substituted carbonitrile or ethyl carboxylate, respectively. The structure of the novel compounds was confirmed by spectroscopic tools (IR, 1H NMR 13C NMR and mass spectra) and elemental analysis.
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,
Discovery of thieno[2,3-d]pyrimidine-based derivatives as potent VEGFR-2 kinase inhibitors and anti-cancer agents
El-Metwally, Souad A.,Abou-El-Regal, Mohsen M.,Eissa, Ibrahim H.,Mehany, Ahmed B.M.,Mahdy, Hazem A.,Elkady, Hazem,Elwan, Alaa,Elkaeed, Eslam B.
, (2021)
Vascular endothelial growth factor-2 (VEGFR-2) is considered one of the most important factors in tumor angiogenesis, and consequently a number of anticancer therapeutics have been developed to inhibit VEGFR-2 signaling. Accordingly, eighteen derivatives of thieno[2,3-d]pyrimidines having structural characteristics similar to VEGFR-2 inhibitors were designed and synthesized. Anticancer activities of the new derivatives were assessed against three human cancer cell lines (HCT-116, HepG2, and MCF-7) using MTT. Sorafenib was used as positive control. Compounds 17c-i, and 20b showed excellent anticancer activities against HCT-116 and HepG2 cell lines, while compounds 17i and 17g was found to be active against MCF-7 cell line. Compound 17f exhibited the highest cytotoxic activities against the examined cell lines, HCT-116 and HepG2, with IC50 values of 2.80 ± 0.16 and 4.10 ± 0.45 μM, respectively. Aiming at exploring the mechanism of action of these compounds, the most active cytotoxic derivatives were in vitro tested for their VEGFR-2 inhibitory activity. Compound 17f showed high activity against VEGFR-2 with an IC50 value of 0.23 ± 0.03 μM, that is equal to that of reference, sorafenib (IC50 = 0.23 ± 0.04 μM). Molecular docking studies also were performed to investigate the possible binding interactions of the target compounds with the active sites of VEGFR-2. The synthesized compounds were analyzed for their ADMET and toxicity properties. Results showed that most of the compounds have low to very low BBB penetration levels and they have non-inhibitory effect against CYP2D6. All compounds were predicted to be non-toxic against developmental toxicity potential model except compounds 17b and 20b.
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.
Synthesis, Antibacterial Activity, and Docking Studies of 1,2,3-triazole-tagged Thieno[2,3-d]pyrimidinone Derivatives
Aruna Kumari,Triloknadh,Harikrishna,Vijjulatha,Venkata Rao
, p. 3672 - 3681 (2017)
Novel (1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methyl-2-(4-oxo-5,6,7,8-tetrahydrobenzo[1,2]thieno[2,3-d]pyrimidin-3(4H)-yl)acetate derivatives were synthesized. All the compounds showed significant antibacterial activity against Gram-negative (Escherichia coli and Klebsiella pneumonia) and Gram-positive (Bacillus subtilis and Bacillus cereus) bacteria. Particularly, (1-(3-nitrophenyl)-1H-1,2,3-triazol-4-yl)methyl-2-(4-oxo-5,6,7,8-tetrahydrobenzo[1, 2]thieno[2,3-d]pyrimidin-3(4H)-yl)acetate was found to be most potent against E.?coli, K.?pneumonia, and B.?subtilis with MIC 25?μg/ml. Molecular docking was also performed on purine riboswitch of B.?subtilis and thiamine pyrophosphate riboswitch of E.?coli.
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.
Utilization of tetrahydrobenzo[4,5]thieno[2,3-d]pyrimidinone as a cap moiety in design of novel histone deacetylase inhibitors
Mohamed, Mamdouh F.A.,Youssif, Bahaa G.M.,Shaykoon, Montaser Sh. A.,Abdelrahman, Mostafa H.,Elsadek, Bakheet E.M.,Aboraia, Ahmed S.,Abuo-Rahma, Gamal El-Din A.
, (2019)
A series of novel 5,6,7,8-Tetrahydro[1]benzothieno[2,3-d]pyrimidin-4(3H)-one derivatives bearing a hydroxamic acid, 2-aminoanilide and hydrazide moieties as zinc-binding group (ZBG) were designed, synthesized and evaluated for the HDAC inhibition activity
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
