title: Novel cyclopropapyrroloindole derivative (AT-3510) bearing methoxycarbonyl and trifluoromethyl groups.
abstract: The seco-Cl 3-methoxycarbonyl-2-trifluoromethylcyclopropapyrroloindole (MCTFCPI) derivatives dl- and/or (S)-10 carrying various acyl moieties at the N6-position were synthesized along with their prodrugs (S)-12, and their antitumor activity was evaluated. Among these derivatives, AT-3510 [(S)-12m], the novel prodrug MCTFCPI derivative carrying a 5-(7-methoxybenzofuran-2-ylcarbonyl)aminoindole-2-carb onyl group at the N6-position, was found to exhibit more excellent antitumor activity against human tumor xenografts than the clinical trial candidates carzelesin (6) and KW-2189 (7) and cisplatin.
authors.affiliation: Central Research Laboratories, Kyorin Pharmaceutical Company Ltd., Mitarai, Nogi, Tochigi 329-0114, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuda
authors.forename: H
authors.initials: H
authors.lastname: Furuta
authors.forename: Y
authors.initials: Y
authors.lastname: Kusama
authors.forename: H
authors.initials: H
authors.lastname: Ebisu
authors.forename: Y
authors.initials: Y
authors.lastname: Oomori
authors.forename: S
authors.initials: S
authors.lastname: Terashima
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001572:Benzofurans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
chemical_list: C118773:AT 3510; D000970:Antineoplastic Agents; D001572:Benzofurans; D011355:Prodrugs; D011758:Pyrroles