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.

Abstract	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.
Authors	Hiroyuki Naito, Satoru Ohsuki, Masamichi Sugimori, Ryo Atsumi, Megumi Minami, Yoshihide Nakamura, Mineko Ishii, Kenji Hirotani, Eiji Kumazawa, Akio Ejima
Journal	Chemical & pharmaceutical bulletin (Chem Pharm Bull (Tokyo)) Vol. 50 Issue 4 Pg. 453-62 (Apr 2002) ISSN: 0009-2363 [Print] Japan
PMID	11963990 (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
Topics	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

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.

Realize the full power of the drug-disease research graph!