CXCR4 inhibitor and application thereof

A technology of solvates and compounds, applied in the field of medicine, can solve the problems of inability to meet the needs of patients and lack of drugs

Active Publication Date: 2020-07-07
ZHUHAI NOBEL INST OF BIOMEDICINE CO LTD
View PDF2 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, there is a great demand for drugs for stem cell mobilization, HIV infection, hematological tumors, solid tumors and immunodeficiency diseases, but there are few drugs on the market, and they cannot meet the needs of patients

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
  • CXCR4 inhibitor and application thereof
  • CXCR4 inhibitor and application thereof
  • CXCR4 inhibitor and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0137]

[0138] Synthesis of Intermediate 71-2:

[0139] Compound 71-1 (500 mg, 2.92 mmol) was dissolved in THF (30 mL) and H 2 O 30mL, add sodium bicarbonate (294mg, 3.50mmol), di-tert-butyl dicarbonate (764mg, 3.50mmol), and stir at room temperature. TLC followed the reaction until the raw material methyl tranexamic acid disappeared, the reaction was stopped, extracted three times with saturated sodium bicarbonate and DCM, the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and purified by column (PE:EA=3:1) , to obtain intermediate 6-2 (751 mg).

[0140] Synthesis of Intermediate 71-2:

[0141] Dissolve 71-1 (750mg, 2.77mmol) in THF (30mL), cool down to 0°C and stir, slowly add LiAlH4 (211mg, 5.54mmol), stir, and react at room temperature. TLC followed the reaction until the starting material 83-1 disappeared, then stopped the reaction, extracted three times with saturated saline and EA, combined the organic phases, dried over anhydrou...

Embodiment 2

[0167]

[0168] Synthesis of Intermediate 96-2:

[0169] Dissolve compound 96-1 (400mg, 0.84mmol) in 10Ml THF, add 2,4-dichloropyrimidine (125mg, 0.84mmol) and DIEA (129mg, 1.00mmol) successively, stir at room temperature, follow the reaction by TLC, to the starting material 96-1 disappeared, stopped the reaction, extracted three times with saturated saline and DCM, combined the organic phases, dried over anhydrous sodium sulfate, concentrated, and purified by column (DCM:CH 3 OH=30:1), the final product 96-2 (392 mg) was obtained as a yellow solid.

[0170] Synthesis of Intermediate 96-3:

[0171] Compound 96-2 (390mg, 0.66mmol) was dissolved in 20Ml 1,4-dioxane, and 2-aminomethylpyridine (71mg, 0.66mmol), cesium carbonate (323mg, 0.99mmol) and [1 , 1'-bis(diphenylphosphino)ferrocene]palladium dichloride (48mg, 0.066mmol), replaced by N2, heated to 100°C for reaction. TLC followed the reaction until the raw material 96-2 disappeared, stopped the reaction, extracted with...

Embodiment 3

[0179]

[0180] Synthesis of Intermediate 17-2:

[0181] Dissolve N-Fmoc-L-alanine (295mg, 0.95mmol) in THF (20Ml), stir, add HATU (431mg, 1.14mmol), HOBT (153mg, 1.14mmol), DIEA (244mg, 1.89mmol) ) and compound 17-1 (528mg, 0.95mmol), stirred at room temperature, TLC followed the reaction until the disappearance of raw material 17-1, stopped the reaction, extracted three times with saturated sodium bicarbonate and DCM, combined the organic phases, dried over anhydrous sodium sulfate, concentrated After column purification (PE:EA=3:1), intermediate 17-2 (679 mg) was obtained.

[0182] Synthesis of Intermediate 17-3:

[0183] Compound 17-2 (650 mg) was dissolved in 1M PIP / THF solution and stirred at room temperature. TLC followed the reaction until the disappearance of raw material 17-2, stopped the reaction, concentrated and purified by column (DCM:CH 3 OH=10:1), to obtain intermediate 17-3 (451 mg).

[0184] Synthesis of Intermediate 17-4:

[0185] Compound 17-3 (450m...

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 relates to a compound, application of the compound in preparation of a drug, a pharmaceutical composition containing the compound, a drug carrier and a drug combination. The compound isa compound shown as a formula (I), and a stereoisomer, a geometrical isomer, a tautomer, nitric oxide, a hydrate, a solvate, a metabolite, a pharmaceutically acceptable salt or a prodrug thereof. Thecompound disclosed by the invention shows a very strong inhibition activity on a CXCR4-SDF-1 alpha axis, has good in-vivo stability, good absorption effect and high bioavailability, can effectively interfere or block the interaction between SDF-1 alpha and CXCR4, has the effects of mobilizing hematopoietic stem cells, treating tumor diseases, inflammatory reactions, autoimmune diseases and the like, and has good application prospects.

Description

technical field [0001] The present invention relates to the field of medicine. In particular, the present invention relates to CXCR4 inhibitors and uses thereof. More specifically, the present invention relates to compounds, the use of compounds in the preparation of drugs, pharmaceutical compositions, drug carriers, drug combinations, methods for screening drugs and screening targets. Background technique [0002] CXC chemokine receptor 4 (CXCR4) and stromal cell-derived factor 1 (SDF-1) belong to the chemokine CXC subfamily and the chemokine receptor G protein-coupled receptor superfamily, respectively. CXCR4 is an important chemokine receptor widely expressed in a variety of hematopoietic cells (neutrophils, monocytes and macrophages, T, B lymphocytes), hematopoietic stem cells, endothelial precursors in blood and bone marrow cells, blood-derived dendritic cells, and Langerhans cells. At the same time, it is also highly expressed in vascular endothelial cells, neurons ...

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): C07D213/38C07D401/12C07D471/04C07F9/6558C07D213/40C07D405/12C07D401/06C07D213/71C07D235/14A61K31/4402A61K31/4709A61K31/506A61K31/517A61K31/4545A61K31/4725A61K31/4439A61K31/675A61K31/4433A61K31/496A61K31/5377A61K31/4406A61K31/551A61K31/4184A61P35/00A61P35/02A61P31/18A61P19/08A61P37/06A61P9/10A61P7/00A61P25/28A61P27/02A61P11/00A61P1/00A61P17/00A61P29/00C12Q1/02
CPCC07D213/38C07D213/40C07D213/71C07D235/14C07D401/06C07D401/12C07D405/12C07D471/04C07F9/65583C12N2503/02G01N33/5008G01N2500/10A61K31/00A61K31/33A61K31/4184A61K31/435A61K31/4402A61K31/4406A61K31/4433A61K31/4439A61K31/4545A61K31/4709A61K31/4725A61K31/495A61K31/496A61K31/506A61K31/517A61K31/5377A61K31/551A61K31/675A61P1/00A61P7/00A61P9/10A61P11/00A61P17/00A61P19/08A61P25/28A61P27/02A61P29/00A61P31/18A61P35/00A61P35/02A61P35/04A61P37/06C07D213/36C07D239/24C07F9/6558C12Q1/02
Inventor 黄子为聂凛凛徐岩谭嘉文梁柏强杨虹叶辉
Owner ZHUHAI NOBEL INST OF BIOMEDICINE CO LTD
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