Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

3-vinyl indazole derivative as well as preparation method and application thereof

An alkyl and phenyl technology, which can be used in drug combinations, pharmaceutical formulations, medical preparations containing active ingredients, etc., and can solve problems such as low activity or expression level, over-activation or up-regulation of expression, etc.

Pending Publication Date: 2020-05-29
SICHUAN UNIV +1
View PDF7 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Most oncogenic RTKs have very low activity or expression in normal tissues but are hyperactivated or upregulated in cancer cells

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
  • 3-vinyl indazole derivative as well as preparation method and application thereof
  • 3-vinyl indazole derivative as well as preparation method and application thereof
  • 3-vinyl indazole derivative as well as preparation method and application thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0160] The preparation of embodiment 1 compound of the present invention

[0161]

[0162] Take compound 1-1 (1.86g, 10mmol), compound 2-1 (3.17g, 12mmol), Pd(dppf)Cl 2 (5mmol%), potassium carbonate (2.76g, 20mmol), add 1,4-dioxane and water (volume ratio is 4:1) in the mixed solvent 50mL, N 2 After the replacement, the reaction was carried out at 100° C. for 6 hours. The reaction was monitored by TLC. After the reaction was complete, the reaction solution was distilled off under reduced pressure, and the residue was dissolved in a mixed solvent of dichloromethane and methanol, filtered through diatomaceous earth, and the filtrate was concentrated, followed by column chromatography (PE:EA=2:1) Intermediate I-1 was obtained (pale yellow solid, 73%), MS m / z (ESI): 244.1 [M+H] + .

[0163]

[0164] Intermediate Ⅰ-1 (1.21g, 5mmol) was dissolved in 30mL of toluene, potassium acetate (0.59g, 6mmol), acetic anhydride (0.94mL, 10mmol) were added, stirred at room temperature f...

Embodiment 2

[0192] The preparation of embodiment 2 compounds of the present invention

[0193]

[0194] Take compound 4-4 (50 mg), add 10 ml of HCl / 1,4-dioxane solution, stir at room temperature for 5 h, concentrate the solvent, dissolve the residue in methanol and perform thin-layer chromatography (DCM:MeOH=8: 1) Obtain compound 4-5 (light brown solid, 52%). 1 H NMR (400MHz, DMSO-d 6 )δ9.58(s,2H),8.26(d,J=8.5Hz,1H),7.83(d,J=7.9Hz,2H),7.77(s,1H),7.68(d,J=16.7Hz, 1H), 7.58(d, J=16.7Hz, 1H), 7.51(dd, J=7.9, 4.4Hz, 3H), 6.87(d, J=2.2Hz, 2H), 6.55(t, J=2.2Hz, 1H), 3.84(s,6H), 3.78–3.63(m,4H), 3.16(s,4H).

[0195] Using a similar method the following compounds can be obtained:

[0196] Compound 4-7

[0197]

[0198] 1H NMR (400MHz, DMSO-d6) δ13.35(s, 1H), 8.28(d, J=8.5Hz, 1H), 7.84–7.78(m, 3H), 7.66(d, J=16.8Hz, 1H) ,7.61–7.51(m,2H),7.40(d,J=8.0Hz,2H),7.23–7.13(m,2H),6.87(dt,J=10.9,2.3Hz,1H),3.87(s,6H ),3.63–3.35(m,3H),2.69(d,J=8.5Hz,3H),1.10–0.80(m,7H).

[0199] The compounds in...

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 3-vinyl indazole derivative as well as a preparation method and application thereof, and belongs to the field of chemical medicines. The invention provides a compound represented by a formula I, an optical isomer of the compound, and a pharmaceutically acceptable salt of the compound or the optical isomer of the compound. Biological experiments prove that the 3-vinyl indazole derivative provided by the invention has a remarkable inhibition effect on the activity of FGFR kinase, can effectively inhibit proliferation of various cancer cells such as breast cancer, lungcancer and gastric cancer, and has a broad-spectrum anti-cancer effect; besides, the 3-vinyl indazole derivative also has an obvious inhibiting effect on proliferation of fibroblasts, the effect of the 3-vinyl indazole derivative is equivalent to that of a drug Nintedanib for treating pulmonary fibrosis clinically at present, and the anti-fibrosis curative effect is remarkable. The 3-vinyl indazole derivative provides a new choice for development and application of anti-cancer and anti-fibrosis drugs.

Description

technical field [0001] The invention relates to 3-vinylindazole derivatives, a preparation method and application thereof, and belongs to the field of chemical medicine. Background technique [0002] At present, the main methods for treating cancer include traditional therapies such as surgery, radiotherapy, and chemotherapy, as well as targeted therapies, including immunotherapy such as PD1 / PD-L1 and CAR-T therapy, small molecule targeted drugs, monoclonal antibodies, and antibody conjugates. drugs etc. Traditional cancer treatment methods have limited effects, are prone to recurrence, metastasis or side effects, and have a great impact on the quality of life of patients. Molecular targeted drugs have certain specificity, and small molecule targeted drugs have always been an important treatment method for the treatment of diseases including cancer. [0003] Receptor tyrosine kinases (RTKs), as a class of targets of molecular targeted drugs, are receptor proteins located o...

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
IPC IPC(8): C07D231/56C07D403/10C07D401/06C07D403/06C07D403/14C07D413/14A61K31/416A61K31/496A61K31/4439A61K31/5377A61P35/00A61P11/00A61P1/16
CPCC07D231/56C07D403/10C07D401/06C07D403/06C07D403/14C07D413/14A61P35/00A61P11/00A61P1/16
Inventor 叶庭洪魏于全刘志昊魏玮余洛汀
Owner SICHUAN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com