Synthesis and biological evaluation of novel pyrazolopyrimidines derivatives as anticancer and anti-5-lipoxygenase agents.
A novel series of 6-aryl-3-methyl-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-4(5H)-ones 3a-h were synthesized in a single step via condensation of carboxamide 2 with some aromatic aldehydes (presence of iodine). Treatment of aminopyrazole 1a with acetic anhydride afforded pyrazolopyrimidines 4 which on treatment with ethyl chloroacetate in refluxing dry DMF furnished a single product identified as ethyl 2-(3,6-dimethyl-4-oxo-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-5(4H)-yl) acetate 5. On the other hand, esterification of compound 6 with different alcohol, led to the formation of new esters linked pyrazolo[3,4-d]pyrimidinones hybrids 7a-f. The reaction of compound 2 with 3-propargyl bromide gave the compound 8 used as a dipolarophile to access to triazoles (4- and 5-regioisomers (9a-e) and (10a-e), respectively) via the 1,3-dipoar cycloaddition reaction. Finally, condensation reaction of aminopyrazole 1b with α-cyanocinnamonitiles gave the new pyrazolo[1,5-a]pyrimidine-3,6-dicarbonitriles 11a-e. Structures of compounds were established on the basis of (1)H/(13)C NMR and ESI-HRMS. Compounds were screened for their cytotoxic (HCT-116 and MCF-7) and 5-lipoxygenase inhibition activities. The structure-activity relationship (SAR) was discussed.
['Rahmouni|Ameur|A|', 'Souiei|Sawssen|S|', 'Belkacem|Mohamed Amine|MA|', 'Romdhane|Anis|A|', 'Bouajila|Jalloul|J|', 'Ben Jannet|Hichem|H|']
D000970:Antineoplastic Agents D001094:Arachidonate 5-Lipoxygenase D049109:Cell Proliferation D004305:Dose-Response Relationship, Drug D004354:Drug Screening Assays, Antitumor D045325:HCT116 Cells D006801:Humans D016859:Lipoxygenase Inhibitors D061986:MCF-7 Cells D015394:Molecular Structure D011720:Pyrazoles D011743:Pyrimidines D013329:Structure-Activity Relationship
Pyrazolopyrimidines Anticancer Anti-5-lipoxygenase Triazoles Pyrazoles Pyrimidines