title: Synthesis and anticancer activity of some new pyrazolo[3,4-d]pyrimidin-4-one derivatives.
abstract: 3,6-Dimethyl-1-phenyl-1H-pyrazolo[3,4-d][1,3]oxazin-4-one (3) was prepared by hydrolysis of ethyl 5-amino-3-methyl-1-phenyl-1H-pyrazole-4-carboxylate (1) to afford the corresponding carboxylic acid 2, which was reacted with acetic anhydride to give 3. The pyrazolo[3,4-d][1,3]oxazin-4-one 3 was reacted with hydroxylamine hydrochloride, urea, thiourea, thiosemicarbazide, phenylhydrazine and aromatic amines to afford the corresponding pyrazolo[3,4-d]pyrimidin-4-ones 4, 5a,b, 6, 7, 8a-e, respectively. Condensation of pyrazoloxazine derivative 3 with 99% hydrazine hydrate afforded the 5-aminopyrazolo[3,4-d] pyrimidine derivative 9. Coupling of 9 with aromatic aldehydes yielded a series of 3,6-dimethyl-5-(4-substitutedbenzylideneamino)-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidin- 4-ones 10a-e. The new compounds were tested for their antitumor activity on the MCF-7 human breast adenocarcinoma cell line. Almost all the tested compounds revealed antitumor activity, especially 3,6-dimethyl-5-(4-nitrobenzylideneamino)-1-phenyl-1,5-dihydropyrazolo[3,4-d]pyrimidin-4-one (10e) which displayed the most potent inhibitory activity with a half maximal inhibitory concentration (IC₅₀) of 11 µM.
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt. khaled.ahmed@bsu.edu.eg.
authors.forename: Khaled R A
authors.initials: KR
authors.lastname: Abdellatif
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt. Emansherif94@yahoo.com.
authors.forename: Eman K A
authors.initials: EK
authors.lastname: Abdelall
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt. mhmdgwd@yahoo.com.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Abdelgawad
authors.affiliation: Cell Biology and Histology Division, Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62514, Egypt. shorouk2002os@yahoo.com.
authors.forename: Rasha R
authors.initials: RR
authors.lastname: Ahmed
authors.affiliation: Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Beni-Suef University, Beni-Suef 62514, Egypt. raniabakr@ymail.com.
authors.forename: Rania B
authors.initials: RB
authors.lastname: Bakr
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D011720:Pyrazoles / Q000737:chemistry*; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D011743:Pyrimidines