Synthesis and antitumor activity of 20(S)-camptothecin derivatives: carbamate-linked, water-soluble derivatives of 7-ethyl-10-hydroxycamptothecin.
Novel 36 derivatives (6), bonding the phenolic hydroxyl group of 7-ethyl-10-hydroxycamptothecin (4) with diamines through a monocarbamate linkage, were synthesized and their antitumor activity was evaluated in vivo. The derivatives were soluble in water as their HCl salts with the E lactone ring intact and exhibited significant antitumor activity. One of the derivatives, 6-27 showed excellent activity against L1210 leukemia and other murine tumors. The structure of its hydrochloride trihydrate (CPT-11) was determined by spectroscopic and crystallographic methods.
Yakult Institute for Microbiological Research, Tokyo, Japan.
S
S
Sawada
S
S
Okajima
R
R
Aiyama
K
K
Nokata
T
T
Furuta
T
T
Yokokura
E
E
Sugino
K
K
Yamaguchi
T
T
Miyasaka
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D002219:Carbamates; D005260:Female; D000077146:Irinotecan; D007939:Leukemia L1210 / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008813:Mice, Inbred ICR; D012995:Solubility; D014867:Water
D000972:Antineoplastic Agents, Phytogenic; D002219:Carbamates; D014867:Water; D000077146:Irinotecan; D002166:Camptothecin