Novel Cyclopropapyrroloindole Derivative (AT-3510) Bearing Methoxycarbonyl and Trifluoromethyl Groups

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],...

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Veröffentlicht in:	Journal of medicinal chemistry 1999-04, Vol.42 (8), p.1448-1458
Hauptverfasser:	Fukuda, Yasumichi, Furuta, Hirosuke, Kusama, Yoshie, Ebisu, Hiroyuki, Oomori, Yasuo, Terashima, Shiro
Format:	Artikel
Sprache:	eng
Schlagworte:	Animals Antineoplastic agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Benzofurans - chemical synthesis Benzofurans - chemistry Benzofurans - pharmacology Biological and medical sciences Drug Screening Assays, Antitumor Female General aspects Humans Medical sciences Mice Mice, Inbred BALB C Pharmacology. Drug treatments Prodrugs - chemical synthesis Prodrugs - chemistry Prodrugs - pharmacology Pyrroles - chemical synthesis Pyrroles - chemistry Pyrroles - pharmacology Stereoisomerism Structure-Activity Relationship Transplantation, Heterologous Tumor Cells, Cultured
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Zusammenfassung:	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-carbonyl 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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm980668c