Rostaurosporine compound as well as preparation method and application thereof

A technology of staurosporine and compounds, applied in the field of staurosporine compounds and their preparation, can solve the problems of strong cytotoxicity and poor selectivity, and achieve good inhibitory effect

Active Publication Date: 2022-08-05
THE KEY LAB OF CHEM FOR NATURAL PROD OF GUIZHOU PROVINCE & CHINESE ACADEMY OF SCI
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Staurosporine is a class of indolecarbazole alkaloids produced by the metabolism of actinomycetes, which has strong cytotoxicity but poor selectivity

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Rostaurosporine compound as well as preparation method and application thereof
  • Rostaurosporine compound as well as preparation method and application thereof
  • Rostaurosporine compound as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0015] Example 1 Preparation of compound 1

[0016] Under argon protection, in a 25mL two-necked reaction flask, add 34.5mg staurosporine (0.074mmol), dissolve with 5mL dichloromethane, add 100μL triethylamine, and add 21.9mg thiazole-2-carbonyl chloride (0.148 mmol), warmed to room temperature for 2 hours, added water to terminate the reaction, extracted with dichloromethane, dried over anhydrous sodium sulfate and concentrated, separated by silica gel column chromatography, and eluted with dichloromethane:ethyl acetate (v / v 5:1) to obtain White powder 3'-N-(2-thiazolecarboxyl)staurosporine (1) (31.2 mg, yield 74.0%).

[0017] 1 H NMR (400MHz, DMSO-d 6 ): δ9.31(d, J=7.8Hz, 1H), 8.64(s, 1H), 8.24 / 8.16(s, 1H), 8.03(m, 3H), 7.63(m, 1H), 7.47(m, 2H), 7.35(t, J=7.8Hz, 1H), 7.30(m, 1H), 7.06 / 7.02(t, J=7.0Hz, 1H), 6.00 / 5.10(d, J=12.0Hz, 1H), 5.02(s, 2H), 4.65 / 4.48(s, 1H), 3.33 / 2.90(s, 3H), 2.85(m, 1H), 2.77(s, 3H), 2.42 / 2.39(s, 3H), 2.35( m,1H); 13 C NMR (100MHz, DMSO-d 6 )...

Embodiment 2

[0018] Example 2 Preparation of compound 2

[0019] Under argon protection, in a 25mL two-necked reaction flask, add 46.6mg of staurosporine (0.1mmol), dissolve with 5mL of dichloromethane, add 100μL of triethylamine, and add 26.4mg of isoxazole-5-formyl chloride at 0°C (0.2mmol), warmed to room temperature and reacted for 2 hours, added water to terminate the reaction, extracted with dichloromethane, dried over anhydrous sodium sulfate, concentrated, separated by silica gel column chromatography, washed with dichloromethane:ethyl acetate (v / v 5:1) A white powder, 3'-N-(5-isoxazolecarboxyl)staurosporine (2) (49.5 mg, yield 88.2%), was obtained.

[0020] 1 H NMR (400MHz, DMSO-d 6 ):δ9.30(d,J=8.0Hz,1H),8.94 / 8.78(s,1H),8.63(s,1H),8.07(d,J=8.0Hz,1H),8.02(d,J= 8.0Hz, 1H), 7.65 / 7.56(d, J=8.0Hz, 1H), 7.49(t, J=8.0Hz, 2H), 7.37(t, J=8.0Hz, 1H), 7.31(t, J= 8.0Hz, 1H), 7.22 / 7.03(s, 1H), 7.08 / 6.96(t, J=7.5Hz, 1H), 5.06 / 4.41(d, J=13.0Hz, 1H), 5.01(s, 2H), 4.51 / 4.46(s,1H), 2.95 / 2.87...

Embodiment 3

[0021] Example 3 Preparation of compound 3

[0022] Under argon protection, in a 100mL two-necked reaction flask, add 1.6g indole-3-carboxylic acid (10.0mmol), dissolve with 30mL dichloromethane, add 1.2g p-dimethylaminopyridine DMP (10.0mmol) and 2.2g di-tert-butyl dicarbonate (Boc 2 O) (10.0 mmol), warmed to room temperature and reacted for 1 hour, added water to stop the reaction, extracted with ethyl acetate, dried over anhydrous sodium sulfate and concentrated, separated by silica gel column chromatography, washed with petroleum ether:ethyl acetate (v / v 4:1) Detoxification gave N-tert-butoxycarbonylindole-3-carboxylic acid (1.7 g, yield 65.1%) as a white solid, ESI-MS m / z 260.0 [M–H] –. Under argon protection, in a 25mL two-necked reaction flask, add 46.6mg staurosporine (0.1mmol), dissolve it with 5mL N,N-dimethylformamide (DMF), add 100μL triethylamine, 52.2mg fresh Prepared N-tert-butoxycarbonyl indole-3-carboxylic acid (0.2 mmol), 38.4 mg (0.2 mmol) 1-(3-dimethyl...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

PUM

No PUM Login to view more

Abstract

The invention discloses a staurosporine compound as well as a preparation method and application thereof. The compound is prepared from staurosporine through an acylation reaction and a halogenation reaction. The compound disclosed by the invention has very strong inhibitory activity on an acute myeloid cell strain MV4-11 with Flt3-ITD mutation, has a relatively weak inhibitory effect on human peripheral blood mononuclear cells (PBMCs), and can be applied to development of high-efficiency and low-toxicity drugs for preventing and treating leukemia.

Description

technical field [0001] The invention belongs to the field of medicine, and in particular relates to a staurosporine compound and a preparation method and application thereof. Background technique [0002] Leukemia is a malignant clonal disease of hematopoietic stem cells. The incidence of leukemia in my country ranks sixth among various tumors, and the incidence is on the rise. According to the priority of onset, it can be divided into acute and chronic leukemia. The cell differentiation of acute leukemia is stagnant in the early stage, mainly primitive and promyocytes, and the disease develops rapidly, with a course of several months. Acute leukemia can be generally divided into two categories: acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). About 17-34% of AML patients have high expression of Fms-like Tyrosine Kinase-3 (Flt3) and internal tandem duplication (ITD) mutation, namely Flt3-ITD gene mutation ( AYH Leung, C-H Man, Y-L Kwong. FLT3 inhibitio...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to view more

Application Information

Patent Timeline
no application Login to view more
Patent Type & Authority Applications(China)
IPC IPC(8): C07D498/22A61P35/02
CPCC07D498/22A61P35/02Y02E10/549Y02A50/30
Inventor 王立平朱伟明李明朋许言超左明星
Owner THE KEY LAB OF CHEM FOR NATURAL PROD OF GUIZHOU PROVINCE & CHINESE ACADEMY OF SCI
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap