- Fradcarbazole A compound and preparation method and application thereof
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The invention discloses a fradcarbazole A compound and a preparation method and application thereof. The fradcarbazole A compound is prepared from staurosporine or halogenated staurosporine which is subjected to a sulfur acylation reaction, a salt forming reaction together with iodomethane, a substitution reaction and a dehydrating cyclization reaction. The fradcarbazole A compound has very high selectivity and inhibitory activity on acute myeloid cell strains, namely MV4-11, with Flt3-ITD mutation, has a weak inhibiting effect on human peripheral blood mononuclear cells (PBMC), and can be developed to be an efficient and low-toxicity drug for preventing and treating leukemia.
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Paragraph 0015
(2019/07/01)
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- Semisynthetic Derivatives of Fradcarbazole A and Their Cytotoxicity against Acute Myeloid Leukemia Cell Lines
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Fourteen derivatives of the marine-derived fradcarbazole A were synthesized from staurosporine. Their structures were identified by NMR and high-resolution electrospray ionization mass spectrometry (HRESIMS). The derivatives were screened in vitro for antiproliferative activity against three human leukemic cell lines (MV4-11, HL-60, K562). All of the derivatives displayed cytotoxicity against the human FLT-3 internal tandem duplication (ITD) mutant acute myeloid leukemia (AML) cell line MV4-11 with IC50 values of 0.32-0.96 μM. The mechanism of action studies indicated that the most effective 3-chloro-5"-fluorofradcarbazole A (6) induced apoptosis of the MV4-11 cells and arrested the cell cycle at the G0/G1 phase. Furthermore, compound 6 can reduce the expression of FLT-3, CDK2, and c-kit. The results suggest that 3-chloro-5"-fluorofradcarbazole A (6) is a potential candidate for developing novel anti-AML agents in the future.
- Li, Mingpeng,Xu, Yanchao,Zuo, Mingxing,Liu, Wen,Wang, Liping,Zhu, Weiming
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p. 2279 - 2290
(2019/09/19)
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- Preparation method of 5-bromoindole derivative
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The invention discloses a preparation method of a 5-bromoindole derivative tert-butyl 2-(5-bromo-1H-indole-3-yl)ethyl carbamate. The preparation method comprises the following steps: taking 5-bromoindole as an initial raw material, and performing a Friedel-Craft reaction, amidation, reduction and a tert-butyloxycarbonyl protection reaction to obtain the target product. The compound is an important medical intermediate compound.
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- Cascade annulation reactions to access the structural cores of stereochemically unusual strychnos alkaloids
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A new cascade annulation reaction has been developed to access the core structures of a novel family of strychnos alkaloids with a unique stereochemical arrangement. The new annulation cascade is facilitated by the development of a robust reaction sequenc
- Delgado, Rieardo,Blakey, Simon B.
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supporting information; experimental part
p. 1506 - 1510
(2009/08/16)
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- Synthesis of the brominated marine alkaloids (±)-arborescidine A, B and C
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A straightforward synthesis of the brominated marine alkaloids arborescidine A (1), B (2) and C (3), starting from 6-bromo-(N-methyl) trypatamine is described. An equilibrium, under both basic and acidic conditions was found to exist between the trans- and cis-isomers 3 and 4. Spectral data indicated that the structure of isomer 4 does not correspond with the compound identified as arborescidine D recently isolated from the marine tunicate Pseudodistoma arborescens.
- Burm, Brigitte E.A.,Meijler, Michael M.,Korver, Jacco,Wanner, Martin J.,Koomen, Gerrit-Jan
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p. 6135 - 6146
(2007/10/03)
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- INDOLE-DERIVED ARYLPIPERAZINES AS LIGANDS FOR 5HT1-LIKE, 5HT1B AND 5HT1D RECEPTORS
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Novel indole-derived azylpiperazines of general formula (I), wherein, inter alia, R 1 is NH 2 or NO 2, R' 1, R 2, R' 2, R 3 and R 4 are H, Z is--C--and X is 0. Methods for preparing such derivatives and the therapeutical uses thereof are also disclosed.
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