title: Mitomycin derivatives having unique condensed-ring structures. Their synthesis and antitumor activity.
abstract: A series of mitomycin derivatives 1-3 having unique condensed-ring structures was synthesized and evaluated for their anticellular and antitumor activity. These compounds were synthesized by the Michael addition of 1.3-dicarbonyl compounds to 6-demethyl-7,7-(ethylenedioxy)-6,7-dihydro-6-methylenemitosanes (4-6, and 14) and the subsequent cyclization. For the preparation of 1. the allyloxycarbonyl (Aloc) group was employable for the protection of the aziridine (1a-N-H), since the deprotection proceeded without decomposition of the substrates under the mild conditions with Pd(0) and HCO2H-NEt3. Among these structurally unique derivatives, compounds 1a, 1b, 1d and 1e were quite potent against HeLa S3 human tumor cells and sarcoma 180 solid tumor in mice.
authors.affiliation: Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Shizuoka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Arai
authors.forename: Y
authors.initials: Y
authors.lastname: Kanda
authors.forename: T
authors.initials: T
authors.lastname: Ashizawa
authors.forename: M
authors.initials: M
authors.lastname: Morimoto
authors.forename: K
authors.initials: K
authors.lastname: Gomi
authors.forename: M
authors.initials: M
authors.lastname: Kono
authors.forename: M
authors.initials: M
authors.lastname: Kasai
mesh_terms: D000818:Animals; D006367:HeLa Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D008937:Mitomycins / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012510:Sarcoma 180 / Q000188:drug therapy
chemical_list: D008937:Mitomycins