Structure-based design, synthesis, and study of pyrazolo[1,5-a][1,3,5]triazine derivatives as potent inhibitors of protein kinase CK2

Nie, Zhe; Perretta, Carin; Erickson, Philip; Margosiak, Stephen A.; Almassy, Robert J.; Lu, Jiajia; Averill, April M.; Yager, Kraig M.; Chu, Shaosong

doi:10.1016/j.bmcl.2007.05.041

Cited by 91 publications

(57 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…150 Condensation of 286 with triethyl orthoformate afforded 290 which reacted with acylhydrazines to afford 291 that could be cyclized into 292 151 …”

Section: Scheme 80mentioning

confidence: 99%

Recent developments in aminopyrazole chemistry

Anwar¹,

Elnagdi²

2009

Arkivoc

View full text Add to dashboard Cite

Recently reported syntheses of 3(5)-aminopyrazoles, 4-aminopyrazoles, and 1-aminopyrazoles as well as of diaminopyrazoles and their general pattern of reactivity towards mono-and bidentate electrophiles have been surveyed. Emphasis has also been laid on techniques for ascertaining the site selectivity in reactions with electrophiles, including single crystal X-ray structure analysis, 1 H-15 N HMBC, and NOE intensity difference experiments as well as other modern 2D NMR techniques. Some thermally induced cycloadditions have also been treated.

show abstract

“…150 Condensation of 286 with triethyl orthoformate afforded 290 which reacted with acylhydrazines to afford 291 that could be cyclized into 292 151 …”

Section: Scheme 80mentioning

confidence: 99%

Recent developments in aminopyrazole chemistry

Anwar¹,

Elnagdi²

2009

Arkivoc

View full text Add to dashboard Cite

show abstract

“…20 The highest efficiency documented in the literature for a CK2 inhibitor belongs to a class of pyrazolo-triazine derivatives reported to affect CK2 with K i values in the nanomolar and subnanomolar range. 21,22 Regrettably, however, the experimental conditions for these assays were not detailed; this hampers reliable comparison with other inhibitors. In this paper the synthesis of a number of tetraiodinatedbenzimidazoles is described for the first time together with a structure-activity analysis in comparison with the corresponding tetrabrominated derivatives.…”

Section: Introductionmentioning

confidence: 99%

Tetraiodobenzimidazoles are potent inhibitors of protein kinase CK2

Gianoncelli

Cozza

Orzeszko

et al. 2009

Bioorganic & Medicinal Chemistry

View full text Add to dashboard Cite

a b s t r a c tA series of novel iodinated benzimidazoles have been prepared by iodination of respective benzimidazole with iodine and periodic acid in sulfuric acid solution. Additionally several 2-substituted-and N-1-carboxymethyl-substituted derivatives of 4,5,6,7-tetraiodobenzimidazole (TIBI) were obtained. For sake of comparison, some new 4,5,6,7-tetrabromobenzimidazoles were also synthesized. The ability of the new compounds to inhibit protein kinase CK2 has been evaluated. The results show that 4,5,6,7-tetraiodobenzimidazoles are more powerful inhibitors of CK2 than their tetrabrominated analogs. Molecular modeling supports the experimental data showing that tetraiodobenzimidazole moiety fills better the binding pocket than respective tetrabromo and tetrachlorocompounds. To note that 4,5,6,7-tetraiodobenzimidazole (TIBI) is one of the most efficient CK2 inhibitors (K i = 23 nM) described to date.

show abstract

“…Recently, Donna et al reported a number of pyrimidinetriones derivatives, including phenylhydrazones of 5-acylpyrimidinetrione that exhibited potent fungal growth inhibition with minimal mammalian cell toxicity [15]. Other derivatives possess promising therapeutic properties including anti-invasive, antiangiogenic, antiviral, central stimulant, anticancer, and calcium antagonist activities [16][17][18]. In view of the importance of barbiturates, we report synthesis, NMR spectra, crystal structure and theoretical calculations of 1,3-dimethyl-5-propionylpyrimidine-2,4,6(1H,3H,5H)-trione ( Figure 1) supported by density functional theory (DFT) calculations correlating the calculated molecular orbital energies (eV) for the surfaces of the frontier molecular orbitals to the electronic excitation transitions from the absorption spectra of the title compound.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Crystal Structure and DFT Studies of 1,3-Dimethyl-5-propionylpyrimidine-2,4,6(1H,3H,5H)-trione

et al. 2017

View full text Add to dashboard Cite

Novel 1,3-Dimethyl-5-propionylpyrimidine-2,4,6(1H,3H,5H)-trione was synthesized and recrystallized from ethanol. The compound was characterized by 1 H NMR, 13 C NMR in CDCl 3 , DMSO-d 6 and acetone-d 6 , elemental analysis and X-ray diffraction. The NMR data observed that the title compound exists in the enol tautomer rather than keto, and it stabilized by strong H-bond as observed form the NMR data at different temperatures. Theoretical calculations (DFT) were carried out using Gaussian09 program package and B3LYP correlation function. Full geometry optimization of the keto and enol forms were carried out using 6-311G++(d,p) basis set. The structure and energy of the transition state between these two tautomers were calculated. The frontier orbital energy and atomic net atomic charges of the tautomers were presented. The experimental results of the title compound have been compared with the theoretical results and it was found that the experimental data are in a good agreement with the calculated values. The transition state calculations also support the stability of enol form compared to keto form at room temperature.

show abstract

Structure-based design, synthesis, and study of pyrazolo[1,5-a][1,3,5]triazine derivatives as potent inhibitors of protein kinase CK2

Cited by 91 publications

References 17 publications

Recent developments in aminopyrazole chemistry

Recent developments in aminopyrazole chemistry

Tetraiodobenzimidazoles are potent inhibitors of protein kinase CK2

Synthesis, Crystal Structure and DFT Studies of 1,3-Dimethyl-5-propionylpyrimidine-2,4,6(1H,3H,5H)-trione

Contact Info

Product

Resources

About