Synthesis and antileukemic activity of (+-)-20-deoxyaminocamptothecin analogues.
The camptothecin analogues (+-)-7-ethyl-10-methoxy-20-deoxyaminocamptothecin (2) and (+-)-7-ethyl-10-hydroxy-20-deoxyaminocamptothecin.HCl (3) were synthesized from indolizine compound 4 via Friedländer condensation to construct a pentacyclic ring system, and were tested in a P388 mouse antileukemia assay. Compounds 2 and 3 were more active and less toxic than (+)-camptothecin (1), and therefore had higher therapeutic ratios.
Ejima
A
A
Terasawa
H
H
Sugimori
M
M
Ohsuki
S
S
Matsumoto
K
K
Kawato
Y
Y
Tagawa
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy; D051379:Mice
D000970:Antineoplastic Agents; C062135:7-ethyl-10-hydroxy-20-deoxyaminocamptothecin; C062134:7-ethyl-10-methoxy-20-deoxyaminocamptothecin; D002166:Camptothecin