14080-59-2Relevant articles and documents
Design, synthesis, docking, molecular dynamics and bioevaluation studies on novel N-methylpicolinamide and thienopyrimidine derivatives with inhibiting NF-κB and TAK1 activities: Cheminformatics tools RDKit applied in drug design
Wang, Linxiao,Zhang, Qian,Wang, Zhe,Zhu, Wufu,Tan, Ninghua
, (2021/07/09)
Using cheminformatics tools RDKit and literature investigation, four series of 24 thienopyrimidine/N-methylpicolinamide derivatives substituted with pyrimidine were designed, synthesized and evaluated for activities against three cancer cell lines (MDA-MB-231, HCT116 and A549), TAK1 kinase and NF-κB signaling pathway. Almost all compounds showed selectivity toward the A549 cell lines and the most promising compound 38 could inhibit TAK1 kinase and NF-κB signaling pathway with the IC50 values of 0.58 and 0.84 μM. Moreover, 38 can induce cell cycle arrest of A549 cells at the G2/M checkpoint with 30.57% and induce apoptosis (34.94%) in a concentration-dependent manner. And western blot showed that compound 38 could inhibit TNF-α-induced IκBα phosphorylation, IκBα degradation, p65 phosphorylation and TAK1 phosphorylation, and reduce the expression of p65. What's more, the studies of docking, molecular dynamics, MM/PBSA and frequency analysis theoretically supported the conclusions of the bioevaluation.
Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor
Fyfe, Tim J.,Kellam, Barrie,Mistry, Shailesh N.,Scammells, Peter J.,Lane, J. Robert,Capuano, Ben
, p. 474 - 490 (2019/03/07)
We recently described a structurally novel series of negative allosteric modulators (NAMs) of the dopamine D2 receptor (D2R) based on thieno[2,3-d]pyrimidine 1, showing it can be structurally simplified to reveal low molecular weight, fragment-like NAMs that retain robust negative cooperativity, such as 3. Herein, we report the synthesis and functional profiling of analogues of 3, placing specific emphasis on examining secondary and tertiary amino substituents at the 4-position, combined with a range of substituents at the 5/6-positions (e.g. aromatic/aliphatic carbocycles). We identify analogues with diverse pharmacology at the D2R including NAMs with sub-μM affinity (9h) and, surprisingly, low efficacy partial agonists (9d and 9i).
Synthesis and antioxidant evaluation of a new class of thienopyrimidinerhodanine hybrids
Nagaraju, Kerru,Bhaskaruni, Venkata H. S. S.,Kishore, Ravada,Maddila, Suresh,Singh, Parvesh,Jonnalagadda, Sreekantha B.
, p. 118 - 126 (2018/03/21)
Background: Antioxidants are proficient of stabilizing agents in the target cells and biological systems. The homeostatic equilibrium between the reactive oxygen species and endogenous antioxidants is important in maintaining healthy tissues. As some antioxidant agent’s show improved resistance, it is necessary to design the new heterocyclic molecules to form potent antioxidant agents with promising pharmacological applications. Moreover, thienopyrimidine derivatives has been the subject of much research due to their significance in different applications and their extensive potential pharmacological and medicinal activities like antibacterial, antifungal, anticancer, anticonvulsant, anti-inflammatory, analgesic, anti-viral, anti-oxidant, anti-diabetic and antimalarial properties. Although, recently rhodanine was reported as privileged hybrid in drug discovery and exhibited pharmacological activities such as anti-malarial, antibacterial, antiviral, antidiabetic agents. Hence, the development of new molecules within the scope of synthetic procedure of thienopyrimidine scaffold for heterocyclic synthesis would be worthy and well desired. Methods: All the target thienopyrimidine-rhodanine derivatives (5a-l) prepared from the Knoevenagel condensation with different substituted benzaldehydes in the presence of glacial acetic acid and 3-(thieno[2,3-d]pyrimidin-4-yl)-2-thioxothiazolidin-4-one (4). Although, all the synthesized compounds tested for their anti-oxidant activity investigated using DPPH radical scavenging, nitric oxide (NO) and ABTS activity. Results: All the thienopyrimidine-rhodanine derivatives (5a-l) were evaluated for their in vitro anti-oxidant activity. In fact, (Z)-5-(4-methylbenzylidene)-3-(thieno[2,3-d]pyrimidin-4-yl)-2-thioxothiazolidin-4-one (5c) with IC50 value 17.64 ± 0.06 μg/mL and (Z)-5-(2-nitrobenzylidene)-3-(thieno[2,3-d]pyrimidin-4-yl)-2-thioxothiazolidin-4-one (5j) with IC50 value 17.54 ± 0.23μg/mL showed excellent antioxidant activity nearly similar to the standard drug as an ascorbic acid (IC50 = 17.45 ± 0.03μg/mL). Conclusion: The objective of the present work was to design, synthesis and screened for their antioxidant activities of novel thienopyrimidine containing rhodanine derivatives with the hope of discovering new structure leads as the most potent antioxidant agents. Our aim has been achieved by the synthesis of thienopyrimidines with diver functionalities by exploiting 2-thioxothiazolidin-4-one chemistry and tested for antioxidant activity. The compounds 5c and 5j were found most potent activity compare to the standard ascorbic acid. Furthermore, the electron withdrawing groups at position-4 in benzene ring enhanced the activity, whereas the compounds 5d, 5f, 5i and 5l showed good activity all the three radical scavenging methods.
