Enterovirus inhibitory activity of C-8- tert -butyl substituted 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2- e ][1,2,4]triazolo[4,3- a ]pyrimidin-5(4 H )-ones

Biswas, Bishyajit Kumar; Malpani, Yashwardhan R.; Ha, Neul; Kwon, Do-Hyun; Shin, Jin Soo; Kim, Hae-Soo; Kim, Chonsaeng; Han, Soo Bong; Lee, Chong-Kyo; Jung, Young‐Sik

doi:10.1016/j.bmcl.2017.05.030

Cited by 10 publications

(3 citation statements)

References 26 publications

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“…The starting compound ethyl 2‐amino‐6‐methyl‐4,5,6,7‐tetrahydro‐1‐benzothiophene‐3‐carboxylate (1) was prepared from 4‐methylcyclohexanone using Gewald's procedure (Huang et al, 2005). Ethyl 6‐methyl‐2‐(3‐phenylthioureido)‐4,5,6,7‐tetrahydro‐1‐benzothiophene‐3‐carboxylate (2) and 2‐mercapto‐7‐methyl‐3‐phenyl‐5,6,7,8‐tetrahydrobenzo[4,5]thieno[2,3‐ d ]pyrimidin‐4( 3H )‐one (3) were also synthesized by reacting compound 1 with phenyl isothiocyanate as reported, followed by cyclization by heating with potassium hydroxide in absolute ethanol (Kumar Biswas et al, 2017). Alkylation of compound 3 with ethyl chloroacetate in anhydrous acetone in the presence of anhydrous potassium carbonate gave ethyl 2‐((7‐methyl‐4‐oxo‐3‐phenyl‐3,4,5,6,7,8‐hexahydro benzo[4,5]thieno[2,3‐ d ]pyrimidin‐2‐yl)thio)acetate (4).…”

Section: Results and Discussion Sectionmentioning

confidence: 99%

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Design and synthesis of novel hexahydrobenzo[4,5]thieno[2,3‐d]pyrimidine derivatives as potential anticancer agents with antiangiogenic activity via VEGFR‐2 inhibition, and down‐regulation of PI3K/AKT/mTOR signaling pathway

Seif

Mahmoud

Wardakhan

et al. 2023

Drug Development Research

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New thieno[2,3‐d]pyrimidine derivatives were designed and synthesized. The National Cancer Institute (NCI) evaluated the synthesized novel compounds against a panel of 60 tumor cell lines for their antiproliferative activity. Compounds 6b, 6f, and 6g showed potent anticancer activity at 10 µM dose, with mean GI of 20.86%, 76.41%, and 31.49%, respectively. Compound 6f was selected for five‐dose concentrations evaluation. Compound 6f scored a submicromolar range of GI50 values against 10 cancer cell lines, indicating broad‐spectrum and potent antiproliferative activity. Compound 6f TGI values were recorded in the cytostatic range of 4.02–95.1 µM. In comparison to sorafenib, the tested compounds 6b, 6f, and 6g inhibited VEGFR‐2 with IC50 values of 0.290 ± 0.032, 0.066 ± 0.004, and 0.16 ± 0.006 µM, correspondingly. Compound 6f significantly reduced the total VEGFR‐2 expression and its phosphorylation. Additionally, 6f reduced the phosphorylation of PI3K, Akt, and mTOR pathway proteins. Moreover, the migratory potential of HUVECs was significantly reduced, after 72 h of treatment with compound 6f, resulting in disrupted wound healing patterns which verified the angiogenesis suppression properties of compound 6f. Compound 6f increased the total apoptosis percentage by 21.27‐fold compared to sorafenib, which caused a 24.11‐fold increase in the total apoptosis percentage. This apoptotic activity was accompanied by a 7.81‐fold increase in the level of apoptotic caspase‐3. Furthermore, the cell cycle analysis revealed that the target derivative 6f reduced cellular proliferation and induced an arrest in HCT‐15 colon cancer cell cycle at the S phase. Molecular modeling was used to determine the binding profile and affinity of derivative 6f toward the VEGFR‐2 active site.

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Section: Results and Discussion Sectionmentioning

confidence: 99%

“…The melting points, element analyses, and spectral data were recorded as reported in our previous work (Emam et al, 2021). Compounds 1, 2 , and 3 were previously reported and prepared according to the literature (Huang et al, 2005; Kumar Biswas et al, 2017).…”

Section: Methodsmentioning

confidence: 99%

Design and synthesis of novel hexahydrobenzo[4,5]thieno[2,3‐d]pyrimidine derivatives as potential anticancer agents with antiangiogenic activity via VEGFR‐2 inhibition, and down‐regulation of PI3K/AKT/mTOR signaling pathway

Seif

Mahmoud

Wardakhan

et al. 2023

Drug Development Research

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“…Evaluation of a series of synthesized [ 1 , 2 , 4 ]triazolo[4,3- a ]pyrimidin-5(4 H )-ones 197 ( Fig. 40 ) for antiviral potential against representative human enteroviruses including Coxsackievirus B1 (Cox B1), Coxsackievirus B3 (Cox B3), Poliovirus 3 (PV3), Human Rhinovirus 14 (HRV14), Human Rhinovirus 21 (HRV 21) and Human Rhinovirus 71 (HRV 71), makes compound 197a (1.6–8.85 μM) promising lead compound for developing broad spectrum anti-enterovirus drugs [ 174 ].…”

Section: Biological Activities Of 124-triazole Derivativesmentioning

confidence: 99%

An insight on medicinal attributes of 1,2,4-triazoles

Aggarwal

Sumran²

2020

European Journal of Medicinal Chemistry

197

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The present review aims to summarize the pharmacological profile of 1,2,4-triazole, one of the emerging privileged scaffold, as antifungal, antibacterial, anticancer, anticonvulsant, antituberculosis, antiviral, antiparasitic, analgesic and anti-inflammatory agents, etc. along with structure-activity relationship. The comprehensive compilation of work carried out in the last decade on 1,2,4-triazole nucleus will provide inevitable scope for researchers for the advancement of novel potential drug candidates having better efficacy and selectivity.

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Novel Triazole‐Containing “Dipeptides”: Synthesis, Molecular Docking and Analgesic Activity Studies

Ghochikyan,

Zhamharyan,

Afrikyan

et al. 2024

ChemBioChem

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Dipeptides of a new structure based on β‐triazolalanines and (L)‐α‐amino acids were synthesized and optimal conditions were developed that ensure both chemical and optical purity of the final products. Molecular docking was carried out and possible intermolecular interactions of dipeptides with potential targets were established. Based on these studies, the analgesic property of chosen dipeptides was studied and it was found that some compounds possess revealed antinociceptive activity in the tail‐flick test.

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Enterovirus inhibitory activity of C-8- tert -butyl substituted 4-aryl-6,7,8,9-tetrahydrobenzo[4,5]thieno[3,2- e ][1,2,4]triazolo[4,3- a ]pyrimidin-5(4 H )-ones

Cited by 10 publications

References 26 publications

Design and synthesis of novel hexahydrobenzo[4,5]thieno[2,3‐d]pyrimidine derivatives as potential anticancer agents with antiangiogenic activity via VEGFR‐2 inhibition, and down‐regulation of PI3K/AKT/mTOR signaling pathway

Design and synthesis of novel hexahydrobenzo[4,5]thieno[2,3‐d]pyrimidine derivatives as potential anticancer agents with antiangiogenic activity via VEGFR‐2 inhibition, and down‐regulation of PI3K/AKT/mTOR signaling pathway

An insight on medicinal attributes of 1,2,4-triazoles

Novel Triazole‐Containing “Dipeptides”: Synthesis, Molecular Docking and Analgesic Activity Studies

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