Synthesis and antitumor activity of 9-acyloxyellipticines.
Various kinds of water-soluble 9-acyloxyellipticine derivatives were synthesized in a search for compounds with potent antitumor activity. Antitumor activities against several tumors in mice (P388 leukemia, colon 26, Lewis lung carcinoma and B16 melanoma) were evaluated by using intravenous administration. Many compounds exhibited good antitumor activities; in particular, the glutarate derivative (5o) showed potent antitumor activity. This compound (5o) may be converted to 9-hydroxyellipticine (2) by enzyme-catalyzed hydrolysis in the body.
Harada
N
N
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Ozaki
K
K
Oda
K
K
Nakanishi
N
N
Ohashi
M
M
Hashiyama
T
T
Tsujihara
K
K
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000378:metabolism; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D004611:Ellipticines / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D007941:Leukemia P388 / Q000188:drug therapy / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism; D008297:Male; D008546:Melanoma, Experimental / Q000188:drug therapy / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship; D014018:Tissue Distribution
D000970:Antineoplastic Agents; D004611:Ellipticines