123629-47-0Relevant articles and documents
Synthesis and inhibitory activity against Epstein-Barr virus of some new 1,2,3,4-tetrahydropyrimidine-2-thiones
Attaby, Fawzy A.,Ramla, Mostafa M.,Harukuni
, p. 2956 - 2967 (2008)
1,2,3,4-Tetrahydropyrimidine-2-thiones 4a-n were synthesized through the reaction of aromatic aldehydes 1a-n, ethyl acetoacetate (2) and thiourea (3). The structures of all newly synthesized heterocyclic compounds elucidated by the use of IR, 1H NMR, mass
Green synthesis and 3D pharmacophore study of pyrimidine and glucoside derivatives with in vitro potential anticancer and antioxidant activities
Salem, Mounir A.,Behalo, Mohamed S.,Elrazaz, Eman
, p. 1223 - 1234 (2019/06/08)
A facile and an efficient one-pot green synthesis of pyrimidine derivatives using the environmentally friendly Cerium(IV) ammonium nitrate (CAN) as catalyst and water as a solvent has been described. Some of the synthesized pyrimidines react with 2,3,4,6-
Ethyl 2-(benzylidene)-7-methyl-3-oxo-2,3-dihydro-5H-thiazolo[3,2-a] pyrimidine-6-carboxylate analogues as a new scaffold for protein kinase casein kinase 2 inhibitor
Jin, Cheng-Hao,Jun, Kyu-Yeon,Lee, Eunjung,Kim, Seongrak,Kwon, Youngjoo,Kim, Kunhong,Na, Younghwa
, p. 4553 - 4565 (2014/12/09)
Protein kinase casein kinase 2 (PKCK2) is a constitutively active, growth factor-independent serine/threonine kinase, and changes in PKCK2 expression or its activity are reported in many cancer cells. To develop a novel PKCK2 inhibitor(s), we first performed cell-based phenotypic screening using 4000 chemicals purchased from ChemDiv chemical libraries (2000: randomly selected; 2000: kinase-biased) and performed in vitro kinase assay-based screening using hits found from the first screening. We identified compound 24 (C24)[(Z)-ethyl 5-(4-chlorophenyl)-2-(3,4-dihydroxybenzylidene)-7-methyl-3-oxo-3, 5-dihydro-2H-thiazolo[3,2-a] pyrimidine-6-carboxylate] as a novel inhibitor of PKCK2 that is more potent and selective than 4,5,6,7-tetrabromobenzotriazole (TBB). In particular, compound 24 [half maximal inhibitory concentration (IC50) = 0.56 μM] inhibited PKCK2 2.2-fold more efficiently than did TBB (IC50 = 1.24 μM), which is quite specific toward PKCK2 with respect to ATP binding, in a panel of 31 human protein kinases. The K i values of compound 24 and TBB for PKCK2 were 0.78 μM and 2.70 μM, respectively. Treatment of cells with compound 24 inhibited endogenous PKCK2 activity and showed anti-proliferative and pro-apoptotic effects against stomach and hepatocellular cancer cell lines more efficiently than did TBB. As expected, compound 24 also enabled tumor necrosis factor-related apoptosis inducing ligand (TRAIL)-resistant cancer cells to be sensitive toward TRAIL. In comparing the molecular docking of compound 24 bound to PKCK2α versus previously reported complexes of PKCK2 with other inhibitors, our findings suggest a new scaffold for specific PKCK2α inhibitors. Thus, compound 24 appears to be a selective, cell-permeable, potent, and novel PKCK2 inhibitor worthy of further characterization.
