Synthesis and Antitumor Activity of Novel Pyrimidinyl Pyrazole Derivatives. II. Optimization of the Phenylpiperazine Moiety of 1-[5-Methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-3-phenylpiperazinyl-1-trans-propenes
| Autor: | Eiji Kumazawa, Satoru Ohsuki, Masamichi Sugimori, Hiroyuki Naito, Ryo Atsumi, Yoshihide Nakamura, Megumi Minami, Akio Ejima, Mineko Ishii, Kenji Hirotani |
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| Rok vydání: | 2002 |
| Předmět: |
Lung Neoplasms
Cell Survival Stereochemistry Fibrosarcoma Antineoplastic Agents Mice Inbred Strains Phenylpiperazine Pyrazole Chemical synthesis Mice chemistry.chemical_compound In vivo Carcinoma Non-Small-Cell Lung Drug Discovery Tumor Cells Cultured Animals Humans Structure–activity relationship Moiety Cytotoxicity Leukemia P388 General Chemistry General Medicine Drug Resistance Multiple Pyrimidines chemistry Drug Resistance Neoplasm Pyrazoles Sarcoma Experimental Growth inhibition Neoplasm Transplantation |
| Zdroj: | Chemical and Pharmaceutical Bulletin. 50:453-462 |
| ISSN: | 1347-5223 0009-2363 |
| Popis: | A series of novel 3-substituted-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propenes in order to improve the in vitro and in vivo activity of our prototype 3-[4-(3-chlorophenyl)-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propene (2) were synthesized and evaluated by assays of growth inhibition against several tumor cell lines in vitro and antitumor activity against some tumor models when dosed both intraperitoneally and orally in vivo. Compounds 7a and 7e, the 3,5-difluorophenyl and 3,5-dichlorophenyl analogues of 2, respectively, showed significantly more potent cytotoxicity than 2 in vitro and potent antitumor activities without causing decrease of body temperature related to side effects. |
| Databáze: | OpenAIRE |
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