A convenient synthesis and molecular modeling study of novel pyrazolo[3,4-d]pyrimidine and pyrazole derivatives as anti-tumor agents

作者：Nassar Ibrahim F^*; Atta Allah Saad R; Elgazwy Abdel Sattar S Hamad

来源：Journal of Enzyme Inhibition and Medicinal Chemistry, 2015, 30(3): 396-405.

DOI：10.3109/14756366.2014.940936

• Anticancer
• cycloadditions
• cyclizations
• heterocycles
• molecular modeling
• pyrazole
• X-ray

An efficient method to obtain ethyl 5-amino-1-tosyl-1H-pyrazole-4-carboxylate (3) was outlined using condensation reactions of 4-methylbenzenesulfonylhydrazide with (E)-ethyl 2-cyano-3-ethoxyacrylate. The cyclocondensation reaction of this substrate and its hydrazide derivative with urea, thiourea, formamide, formic acid, D-glucose, o-phenylenediamine, 4-dimethylaminobenzaldehyde, anthracene-9-carbaldehyde, thioglycolic acid and carbon disulphide then with hydrazine hydrate analogues furnished a series of pyrazolo[3,4-d]pyrimidine, pyrazolo[3,4-d]oxazin-4-one, pyrazole-4-glucoside, 4-benzo[d]imidazole, 1,3-thiazolidinone, 1,3,4-oxadiazol-2(3H)-thione and 1,2,4-triazol-5(4H)-thione derivatives respectively. The structure of the compound 3 was supported by X-Ray crystallographic data. Orally administrated, one of each of the series of pyrazoles showed significant effects in mouse tumor model cancer cell lines (EAC) and two human cancer cell lines of Colon cancer (HCT-29) and Breast cancer (MCF-7) with docking studies.

• 出版日期2015-6