Synthesis and biological evaluation of novel pyrazolopyrimidines derivatives as anticancer and anti-5-lipoxygenase agents |
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| Institution: | 1. Laboratoire de Chimie Hétérocyclique, Produits Naturels et Réactivité, Equipe: Chimie Médicinale et Produits Naturels, Faculté des Sciences de Monastir, Université de Monastir, Avenue de l’Environnement, 5019 Monastir, Tunisia;2. Université de Toulouse, Faculté de pharmacie de Toulouse, Laboratoire des Interactions Moléculaires et Réactivité Chimique et Photochimique UMR CNRS 5623, Université Paul-Sabatier, 118 route de Narbonne, F-31062 Toulouse, France;1. Pharmaceutical Chemistry Department, Faculty of Pharmacy Ain Shams University, Abbassia, Cairo 11566, Egypt;2. Pharmaceutical Chemistry Department, Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University, Cairo 12311, Egypt;3. National Organization for Drug Control & Research, P.O. Box: 29, Cairo, Egypt;4. Medical Union Pharmaceuticals Company, Abu Sultan, Al Ismaillia, Egypt;1. Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr Elini St., Cairo 11562, Egypt;2. National Cancer Institute, Cairo University, Fom Elkhalig, Kasr Elaini St., Cairo 11796, Egypt;3. Pharmacology and Toxicology Department, Faculty of Pharmacy, Al-Azhar University, Nasr City, Cairo 11787, Egypt;1. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt;2. Department of Medical Biochemistry, Faculty of Medicine, Alexandria University, Alexandria, Egypt;1. Laboratory of Heterocyclic Chemistry, Natural Products and Reactivity (LR11Es39), Team: Medicinal Chemistry and Natural Products, Faculty of Science of Monastir, University of Monastir, Avenue of Environment, 5019, Monastir, Tunisia;2. King Saud University, Department of Zoology, College of Science, Riyadh, Saudi Arabia;1. Department of Organometallic and Organometalloid Chemistry, National Research Centre, Dokki 12622, Cairo, Egypt;2. Department of Green Chemistry, National Research Centre, Dokki 12622, Cairo, Egypt;3. Department of Mathematics and Natural Science, Faculty of Science and Technology, University of Stavanger, N-4036 Stavanger, Norway;4. Department of Tanning Materials and Leather Technology, National Research Centre, Dokki 12622, Cairo, Egypt |
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| Abstract: | A novel series of 6-aryl-3-methyl-1-phenyl-1H-pyrazolo3,4-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-pyrazolo3,4-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 pyrazolo3,4-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 pyrazolo1,5-a]pyrimidine-3,6-dicarbonitriles 11a-e. Structures of compounds were established on the basis of 1H/13C 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. |
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| Keywords: | Pyrazoles Pyrimidines Pyrazolopyrimidines Triazoles Anticancer Anti-5-lipoxygenase |
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