50427-80-0Relevant articles and documents
Synthesis of pyrazole-carboxamides and pyrazole-carboxylic acids derivatives: Simple methods to access powerful building blocks
Ferreira, Byanca Silva,Silva, Rafaela Corrêa,Souto, Bernardo Araújo,Dos Santos, Maurício Silva
, p. 335 - 343 (2021/09/07)
Hybrid systems containing pyrazole moiety show a wide spectrum of biological activities. To access novel hybrids with pyrazole ring, in this work we synthesized twenty pyrazole-carboxylic acids and twenty pyrazole-carboxamides, using simple synthetic methods, to be used as building blocks in the development of new structures.
Design and synthesis of novel pyrazolo[3,4-d]pyrimidin-4-one bearing quinoline scaffold as potent dual PDE5 inhibitors and apoptotic inducers for cancer therapy
Ibrahim, Tarek S.,Hawwas, Mohamed M.,Taher, Ehab S.,Alhakamy, Nabil A.,Alfaleh, Mohamed A.,Elagawany, Mohamed,Elgendy, Bahaa,Zayed, Gamal M.,Mohamed, Mamdouh F.A.,Abdel-Samii, Zakaria K.,Elshaier, Yaseen A.M.M.
, (2020/10/21)
PDE5 targeting represents a new and promising strategy for apoptosis induction and inhibition of tumor cell growth due to its over-expression in diverse types of human carcinomas. Accordingly, we report the synthesis of series of pyrazolo[3,4-d]pyrimidin-4-one carrying quinoline moiety (11a-r) with potential dual PDE5 inhibition and apoptotic induction for cancer treatment. These hybrids were structurally elucidated and characterized with variant spectroscopic techniques as 1H NMR, 13C NMR and elemental analysis. The assessment of their anticancer activities has been declared. All the rationalized compounds 11a-r have been selected for their cytotoxic activity screening by NCI against 60 cell lines. Compounds 11a, 11b, 11j and 11k were the most active hybrids. Among all, compound 11j was further selected for five dose tesing and it displayed outstanding activity with strong antitumor activity against the nine tumor subpanels tested with selectivity ratios ranging from 0.019 to 8.3 at the GI50 level. Further, the most active targets 11a, b, j and k were screened for their PDE5 inhibitory activity, compound 11j (with IC50 1.57 nM) exhibited the most potent PDE5 inhibitory activity. Moreover, compound 11j is also showed moderate EGFR inhibition with IC50 of 5.827 ± 0.46 μM, but significantly inhibited the Wnt/β-catenin pathway with IC501286.96 ± 12.37 ng/mL. In addition, compound 11j induced the intrinsic apoptotic mitochondrial pathway in HepG2 cells as evidenced by the lower expression levels of the anti-apoptotic Bcl-2 protein, and the higher expression of the pro-apoptotic protein Bax, p53, cytochrome c and the up-regulated active caspase-9 and caspase-3 levels. All results confirmed by western blotting assay. Compound 11j exhibit pre G1 apoptosis and cell cycle arrest at G2/M phase. In conclusion, hybridization of quinoline moiety with the privileged pyrazolo[3,4-d]pyrimidinon-4-one structure resulted in highly potent anticancer agent, 11j, which deserves more study, in particular, in vivo and clinical investiagtions, and it is expected that these results would be applied for more drug discovery process.
Design and synthesis of pyrazolo[3,4-d]pyrimidinone derivatives: Discovery of selective phosphodiesterase-5 inhibitors
AbdEl-Ghany, Ahmed A.,Elshaier, Yaseen A. M. M.,Farag, Nahla A.,Hammad, Ali H.,Hassan Haredy, Haredy,Mohamed, Khaled O.,Shaaban, Mohamed A.
, (2020/06/26)
A novel series of 1,6-disubstituted pyrazolo[3,4-d]pyrimidin-7-one derivatives, 2a-h, 4a-d, 5 and 6, were successfully synthesized, which showed promising, and potent inhibition of phosphodiesterase 5 (PDE5). The inhibitory activities of 5, 4b, 2a, 2d, 2f
3-(SUBSTITUTED AMINO)-PYRAZOLO[3,4-d]PYRIMIDINES AS EPHB AND VEGFR2 KINASE INHIBITORS
-
Page/Page column 51, (2010/11/27)
The invention relates to novel pyrazolo[3,4-d]pyrimidines of the formula in which all of the variables are as defined in the specification, in free form or in salt form, to their preparation, to their use as medicaments and to medicaments comprising them.
1,4 SUBSTITUTED PYRAZOLOPYRIMIDINES AS KINASE INHIBITORS
-
Page/Page column 52, (2008/06/13)
The invention relates to 1,4-substituted pyrazolopyrimidine compounds of the formula (I), pharmaceuticals comprising a 1,4-substituted pyrazolopyrimidine compound, the use of a 1,4-substituted pyrazolopyrimidine compound in the treatment or the use thereof in the manufacture of a pharmaceutical formulation for the treatment of a disease that depends on inadequate activity of a protein kinase, methods of treatment comprising administering a 1,4-substituted pyrazolopyrimidine compound, methods for the manufacture of a novel compound of that class, and novel intermediates and partial steps for their synthesis.
