Synthesis and structure-activity relationships of 3-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridines as novel antitumor agents.
In order to obtain clinically useful antitumor agent, we have designed and synthesized various 3-substituted 1,4-dihydro-4-oxo-1-(2-thiazolyl)-1,8-naphthyridines, and evaluated their cytotoxic activity. The series of novel 3-substituted derivatives synthesized in this study showed good antitumor activity against murine P388 leukemia. Particularly, the 3-formyl 1,8-naphthyridine displayed an antitumor activity equal to that of the 3-carboxy 1,8-naphthyridine against murine and human tumor cell lines as well as in vivo test for mouse leukemia. These results demonstrate that the carboxy group at the C-3 position of 1,8-naphthyridine ring is not essential for antitumor activity. In addition, the trend of cytotoxic activity for the 3-substituted 1,8-naphthyridines was different from that of antibacterial activity.
Tsuzuki
Yasunori
Y
Chemistry Research Laboratories, Dainippon Pharmaceutical Co, Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan. yasunori-tuduki@dainippon-pharm.co.jp
Tomita
Kyoji
K
Sato
Yuji
Y
Kashimoto
Shigeki
S
Chiba
Katsumi
K
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D045744:Cell Line, Tumor; D006801:Humans; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009287:Naphthyridines