Synthesis and antitumor activity of novel pyrimidinyl pyrazole derivatives. III. Synthesis and antitumor activity of 3-phenylpiperazinyl-1-trans-propenes.
A series of novel 3-[4-phenyl-1-piperazinyl]-1-[5-methyl-1-(2-pyrimidinyl)-4-pyrazolyl]-1-trans-propenes and related compounds were synthesized and evaluated by their cytotoxic activity against several tumor cell lines in vitro and in vivo antitumor activity against some tumor models when administered both intraperitoneally and orally. Compounds with the 3-chloropyridin-2-yl group (9g) and the 3-fluoro-5-substituted phenylpiperazinyl group (29b, c, and e) showed significantly potent cytotoxicity by in vitro testing. Among them, the 3-cyano-5-fluorophenyl derivative (29b) exhibited potent antitumor activity against several tumor cells including human carcinoma without causing undesirable effects in mice.
Naito
Hiroyuki
H
Medicinal Chemistry Research Laboratory, Daiichi Pharmaceutical Co. Ltd, Tokyo, Japan. naitoxns@daiichipharm.co.jp
Ohsuki
Satoru
S
Atsumi
Ryo
R
Minami
Megumi
M
Mochizuki
Mineko
M
Hirotani
Kenji
K
Kumazawa
Eiji
E
Ejima
Akio
A
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010879:Piperazines / Q000138:chemical synthesis* / Q000494:pharmacology*; D011407:Propane / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D010879:Piperazines; D011407:Propane