Synthesis and in vitro anticancer activity of pyrazolo[1,5-a]pyrimidines and pyrazolo[3,4-d][1,2,3]triazines

ABSTRACT A novel series of pyrazolo[1,5-a]pyrimidines 14a–j and pyrazolo[1,5-a]quinazolines 18a, b were synthesized via condensation of 5-amino-1H-pyrazoles 10a, b with 3-(dimethylamino)-1-aryl-prop-2-en-1-ones 11a–e and 2-((dimethylamino)methylene)-5,5-dimethylcyclohexane-1,3-dione (15), respectively, in glacial acetic acid. Finally, treatment of 10a, b with sodium nitrite (NaNO2) afforded pyrazolo[3,4-d]triazines 20a, b. Structures of compounds were confirmed by their spectral data. These compounds were screened for their in vitro cytotoxic activities against human cancer cell lines (HepG-2 and MCF-7) using 3-[4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The results reveal that, the compounds 14b and 14h were the most potent in comparison with doxorubicin. The structure–activity relationship was discussed. GRAPHICAL ABSTRACT

[1]  M. Geng,et al.  Synthesis and structure-activity relationship study of pyrazolo[3,4-d]pyrimidines as tyrosine kinase RET inhibitors. , 2017, Bioorganic & medicinal chemistry letters.

[2]  Ashraf S. Hassan,et al.  Synthesis and antitumor activity of some new pyrazolo[1,5-a]pyrimidines , 2017 .

[3]  Xiaoyun Lu,et al.  Pyrazolo[1,5-a]pyridine-3-carboxamide hybrids: Design, synthesis and evaluation of anti-tubercular activity. , 2017, European journal of medicinal chemistry.

[4]  V. Gaikwad,et al.  An efficient synthesis of pyrazolo[1,5-a]pyrimidines and evaluation of their antimicrobial activity , 2016, Journal of Chemical Sciences.

[5]  J. Bouajila,et al.  Synthesis and biological evaluation of novel pyrazolopyrimidines derivatives as anticancer and anti-5-lipoxygenase agents. , 2016, Bioorganic chemistry.

[6]  A. Kamal,et al.  Synthesis and mechanistic aspects of 2-anilinonicotinyl-pyrazolo[1,5-a]pyrimidine conjugates that regulate cell proliferation in MCF-7 cells via estrogen signaling. , 2016, Bioorganic & medicinal chemistry letters.

[7]  Ashraf S. Hassan,et al.  SYNTHESIS, CHARACTERIZATION AND BIOLOGICAL EVALUATION OF NEW FUSED TRIAZINE DERIVATIVES BASED ON 6-METHYL-3-THIOXO-1,2,4-TRIAZIN-5-ONE. , 2016, Acta poloniae pharmaceutica.

[8]  Ashraf S. Hassan,et al.  Synthesis, Characterization, and Cytotoxicity of Some New 5-Aminopyrazole and Pyrazolo[1,5-a]pyrimidine Derivatives , 2014, Scientia pharmaceutica.

[9]  H. Abd-Alla,et al.  In vitro anti-nitrosative, antioxidant, and cytotoxicity activities of plant flavonoids: a comparative study , 2014, Medicinal Chemistry Research.

[10]  Ashraf S. Hassan,et al.  Synthesis, characterization and cytotoxicity of mixed ligand Mn(II), Co(II) and Ni(II) complexes , 2014 .

[11]  H. Awad,et al.  Synthesis, tumor inhibitory and antioxidant activity of new polyfunctionally 2-substituted 5,6,7,8-tetrahydronaphthalene derivatives containing pyridine, thioxopyridine and pyrazolopyridine moieties. , 2013, Acta poloniae pharmaceutica.

[12]  M. Tahir,et al.  Synthesis, antibacterial activity and cytotoxicity of new fused pyrazolo[1,5-a]pyrimidine and pyrazolo[5,1-c][1,2,4]triazine derivatives from new 5-aminopyrazoles. , 2013, European journal of medicinal chemistry.

[13]  Ashraf S. Hassan,et al.  Synthesis, Structural Elucidation, and In Vitro Antitumor Activities of Some Pyrazolopyrimidines and Schiff Bases Derived from 5-Amino-3-(arylamino)-1H-pyrazole-4-carboxamides , 2013, Scientia pharmaceutica.

[14]  C. Brullo,et al.  Hit Identification and Biological Evaluation of Anticancer Pyrazolopyrimidines Endowed with Anti‐inflammatory Activity , 2010, ChemMedChem.

[15]  E. Lees,et al.  Discovery of Dinaciclib (SCH 727965): A Potent and Selective Inhibitor of Cyclin-Dependent Kinases. , 2010, ACS medicinal chemistry letters.

[16]  A. Abdelhamid,et al.  Synthesis and Antimicrobial Activity of Some New 5-Arylazothiazole, Pyrazolo[1,5-a] Pyrimidine, [1,2,4]Triazolo[4,3-a]Pyrimidine, and Pyrimido[1,2-a]Benzimidazole Derivatives Containing the Thiazole Moiety , 2010 .

[17]  G. Elgemeie,et al.  Design and Synthesis of the First Thiophene Thioglycosides , 2009 .

[18]  S. Bondock,et al.  Synthesis and antimicrobial activity of some new heterocycles incorporating antipyrine moiety. , 2008, European journal of medicinal chemistry.

[19]  G. Elgemeie,et al.  Direct Route to a New Class of Acrylamide Thioglycosides and Their Conversions to Pyrazole Derivatives , 2008 .