title: Synthesis and biological activities of topoisomerase I inhibitors, 6-arylmethylamino analogues of edotecarin.
abstract: The replacement of 1,3-dihydroxy-2-propylamino moiety at the N6-position of edotecarin (1) by arylmethylamino groups yielded a number of more potent topoisomerase I inhibitors with better cytotoxic (CTX) activities in vitro than edotecarin. Among them, the three most potent pyridylmethyl analogues, compounds 22g, 22m, and 23c, showed better antitumor activities against MKN-45 human stomach cancer or MX-1 human breast cancer xenografted mice than those of edotecarin. Furthermore, compounds 22m and 23c exhibited complete response against MX-1 cells implanted in mice.
authors.affiliation: Tsukuba Research Institute, Banyu Pharmaceutical Co. Ltd, Okubo-3, Tsukuba 300-2611, Ibaraki, Japan. satoshi_sunami@merck.com
authors.forename: Satoshi
authors.initials: S
authors.lastname: Sunami
authors.forename: Teruyuki
authors.initials: T
authors.lastname: Nishimura
authors.forename: Ikuko
authors.initials: I
authors.lastname: Nishimura
authors.forename: Satoru
authors.initials: S
authors.lastname: Ito
authors.forename: Hiroharu
authors.initials: H
authors.lastname: Arakawa
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Ohkubo
mesh_terms: D000588:Amines / Q000737:chemistry*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D002227:Carbazoles / Q000737:chemistry*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D006801:Humans; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D051379:Mice; D011725:Pyridines / Q000737:chemistry; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors; D023041:Xenograft Model Antitumor Assays
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D002227:Carbazoles; D004791:Enzyme Inhibitors; D006841:Hydrocarbons, Aromatic; D011725:Pyridines; D059004:Topoisomerase I Inhibitors; C121395:edotecarin