13-08-2015 дата публикации
Номер: US20150225455A1
The present invention provides a dolastatin-10 derivative having excellent anticancer activity, a method of producing the same and anticancer drug composition containing the same as an active ingredient. 2. The dolastatin-10 derivative or a pharmaceutically acceptable salt thereof of claim 1 , wherein{'sub': 1', '3', '4', '1', '4, 'R, Rand Rare each C-Calkyl,'}{'sub': 2', '5', '1', '4, 'Rand Rare each independently hydrogen or C-Calkyl,'}{'sub': 6', '1', '4, 'Ris hydrogen, hydroxy, C-Calkoxy, amino, oxo(═O) or hydroxyimino(═N—OH),'}{'sub': 1', '4', '1', '4, 'Ar is phenyl unsubstituted or substituted with at least one selected from the group consisting of C-Calkyl, C-Calkoxy, and halogen,'}X is a carbon atom, and{'sub': 7', '1', '4', '1', '4, 'Ris hydroxy, amino, C-Calkoxy or C-Calkylamino.'}3. The dolastatin-10 derivative or a pharmaceutically acceptable salt thereof of claim 1 , wherein{'sub': 1', '3', '4, 'R, Rand Rare each methyl,'}{'sub': 2', '5, 'Rand Rare each independently hydrogen or methyl,'}{'sub': '6', 'Ris hydrogen, hydroxy, methoxy, amino, oxo (═O) or hydroxyimino (═N—OH),'}Ar is phenyl unsubstituted or substituted with at least one selected from the group consisting of methyl, methoxy and halogen,X is a carbon atom, and{'sub': '7', 'Ris hydroxy, amino, methoxy, or N-methylamino.'}5. The dolastatin-10 derivative or a pharmaceutically acceptable salt thereof of claim 1 , being selected from the group consisting of:(S)—N-((3R,4S,5S)-1-((2R,4R)-2-((1R,2R)-3-((2,6-difluorophenethyl)amino)-1-methoxy-2-methyl-3-oxopropyl)-4-methoxypyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptan-4-yl)-N,3-dimethyl-2-((S)-3-methyl-2-(methylamino)butaneamido)butanamide (I-1);(S)—N-((3R,4S,5S)-1-((2R,4R)-2-((1R,2R)-3-((3-fluorophenethyl)amino)-1-methoxy-2-methyl-3-oxopropyl)-4-methoxypyrrolidin-1-yl)-3-methoxy-5-methyl-1-oxoheptan-4-yl)-N,3-dimethyl-2-((S)-3-methyl-2-(methylamino)butaneamido)butanamide (I-2);(S)—N-((3R,4S,5S)-1-((2R,4R)-2-((1R,2R)-3-((4-fluorophenethyl)amino)-1- ...
Подробнее