title: Synthesis of new camptothecin analogs with improved antitumor activities.
abstract: Novel hexacyclic camptothecin analogs containing cyclic amidine, urea, or thiourea moiety were designed and synthesized based on the proposed 3D-structure of the topoisomerase I (Topo I)/DNA/camptothecin ternary complex. The analogs were prepared from 9-nitrocamptothecin via 7,9-diaminocamptothecin derivatives as a key intermediate. Among them, 7c exhibited in vivo antitumor activities superior to CPT-11 in human cancer xenograft models in mice at their maximum tolerated doses though its in vitro antiproliferative activity was comparable to SN-38 against corresponding cell lines.
authors.affiliation: Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd, 200 Kajiwara, Kamakura, Kanagawa 247-8530, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Niizuma
authors.forename: Masao
authors.initials: M
authors.lastname: Tsukazaki
authors.forename: Hitomi
authors.initials: H
authors.lastname: Suda
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murata
authors.forename: Jun
authors.initials: J
authors.lastname: Ohwada
authors.forename: Sawako
authors.initials: S
authors.lastname: Ozawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Fukuda
authors.forename: Chikako
authors.initials: C
authors.lastname: Murasaki
authors.forename: Masami
authors.initials: M
authors.lastname: Kohchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Morikami
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshinari
authors.forename: Mika
authors.initials: M
authors.lastname: Endo
authors.forename: Masako
authors.initials: M
authors.lastname: Ura
authors.forename: Hiromi
authors.initials: H
authors.lastname: Tanimura
authors.forename: Yoko
authors.initials: Y
authors.lastname: Miyazaki
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Takasuka
authors.forename: Akira
authors.initials: A
authors.lastname: Kawashima
authors.forename: Eitaro
authors.initials: E
authors.lastname: Nanba
authors.forename: Kounosuke
authors.initials: K
authors.lastname: Nakano
authors.forename: Kotaro
authors.initials: K
authors.lastname: Ogawa
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kobayashi
authors.forename: Hisafumi
authors.initials: H
authors.lastname: Okabe
authors.forename: Isao
authors.initials: I
authors.lastname: Umeda
authors.forename: Nobuo
authors.initials: N
authors.lastname: Shimma
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D006801:Humans; D051379:Mice; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D014183:Transplantation, Heterologous
chemical_list: D000970:Antineoplastic Agents; C541284:CH 0793076; D059004:Topoisomerase I Inhibitors; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin