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.

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.
AuthorsHiroyuki Naito, Satoru Ohsuki, Masamichi Sugimori, Ryo Atsumi, Megumi Minami, Yoshihide Nakamura, Mineko Ishii, Kenji Hirotani, Eiji Kumazawa, Akio Ejima
JournalChemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 50 Issue 4 Pg. 453-62 (Apr 2002) ISSN: 0009-2363 [Print] Japan
PMID11963990 (Publication Type: Journal Article)
Chemical References
  • 3-(4-(3,5-dichlorophenyl)-1-piperazinyl)-1-(5-methyl-1-(2-pyrimidinyl)-4-1H-pyrazolyl)-1-trans-propen
  • 3-(4-(3,5-difluorophenyl)-1-piperazinyl)-1-(5-methyl-1-(2-pyrimidinyl)-4-1H-pyrazolyl)-1-trans-propen hydrochloride
  • Antineoplastic Agents
  • DZ 3358
  • Pyrazoles
  • Pyrimidines
  • Animals
  • Antineoplastic Agents (pharmacology)
  • Carcinoma, Non-Small-Cell Lung (pathology)
  • Cell Survival (drug effects)
  • Drug Resistance, Multiple
  • Drug Resistance, Neoplasm
  • Fibrosarcoma (drug therapy)
  • Humans
  • Leukemia P388 (drug therapy)
  • Lung Neoplasms (pathology)
  • Mice
  • Mice, Inbred Strains
  • Neoplasm Transplantation
  • Pyrazoles (chemical synthesis, pharmacology)
  • Pyrimidines (chemical synthesis, pharmacology)
  • Sarcoma, Experimental (drug therapy)
  • Tumor Cells, Cultured

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