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

Synthesis and medical application of a kind of pyrrolo[2,1-f][1,2,4]triazine core compound

A compound, pyrrole technology, applied in the field of medicinal chemistry, can solve the problems of narrow clinical indications and incomplete development of BTK inhibitors

Inactive Publication Date: 2018-12-04
NINGBO WESDON POWDER PHARMA COATINGS CO LTD
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the value of BTK inhibitors has not been fully developed at present, and the clinical indications are relatively narrow, so it is necessary to continue to develop BTK inhibitors with high selectivity, high biological activity and low toxicity

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
  • Synthesis and medical application of a kind of pyrrolo[2,1-f][1,2,4]triazine core compound
  • Synthesis and medical application of a kind of pyrrolo[2,1-f][1,2,4]triazine core compound
  • Synthesis and medical application of a kind of pyrrolo[2,1-f][1,2,4]triazine core compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Preparation of Pyrrolo[2,1-f][1,2,4]triazine core compound BTK irreversible inhibitor compound (1)

[0032]

[0033] White crystalline powder, M.P.186-188℃. 1 H-NMR (400MHz, DMSO-d 6 )δ: 10.17 (1H, s), 9.02 (1H, s), 8.67 (1H, s), 7.15-7.34 (2H, m), 6.45-6.96 (6H, m), 6.64 (1H, d), 6.51 (1H, m), 6.17-6.25 (2H, m), 6.02 (1H, d, J = 15.6 Hz), 5.51 (1H, d, J = 6.8 Hz), 4.43 (2H, t), 3.39 (2H, t),2.38(2H,t),2.27(3H,s),1.64(2H,m); 13 C-NMR(100MHz, DMSO-d 6 )δ: 166.8, 161.6, 149.5, 142.8, 139.7, 136.8, 131.2, 129.9, 128.6, 126.9, 122.8, 118.2, 113.7, 111.9, 110.3, 108.2, 100.8, 86.6, 58.5, 57.8, 42.4, 19.9; HRMS (ESI )calcd.for C 26 H 28 N 8 O[M+H] + ,468.2386; found,468.2392.

Embodiment 2

[0035] Preparation of irreversible inhibitor compound (2) of pyrrolo[2,1-f][1,2,4]triazine core compound BTK

[0036]

[0037] White crystalline powder, M.P.165-167℃. 1 H-NMR (400MHz, DMSO-d 6 )δ: 10.33 (1H, s), 9.25 (1H, s), 8.79 (1H, s), 7.19-7.38 (2H, m), 6.44-6.95 (6H, m), 6.66 (1H, d), 6.53 (1H,m),6.16-6.25(2H,m),6.02(1H,d,J=12.5Hz), 5.50(1H,d,J=8.7Hz), 3.46(4H,t), 2.38(4H, t), 2.26(3H,s); 13 C-NMR(100MHz, DMSO-d 6 )δ:166.8,161.6,149.5,142.8,139.7,136.8,131.2,129.9,128.6,126.9,122.8,118.2,113.7,111.9,110.3,108.2,101.1,57.4,52.1,46.8; HRMS(ESI)calcd.for C 26 H 28 N 8 O[M+H] + ,468.2386; found,468.2392.

Embodiment 3

[0039] Preparation of irreversible inhibitor compound (3) of pyrrolo[2,1-f][1,2,4]triazine core compound BTK

[0040]

[0041] White crystalline powder, M.P.170-172℃. 1 H-NMR (400MHz, DMSO-d 6 )δ: 10.29 (1H, s), 9.18 (1H, s), 8.82 (1H, s), 7.18-7.37 (2H, m), 6.44-6.95 (6H, m), 6.65 (1H, d), 6.53 (1H,m),6.16-6.25(2H,m), 6.04(1H,d,J=14.4Hz), 5.53(1H,d,J=9.8Hz), 3.47(4H,t), 2.80(4H, t),1.93(1H,s); 13 C-NMR(100MHz, DMSO-d 6 )δ: 166.8, 161.6, 149.5, 142.8, 139.7, 136.8, 131.2, 129.9, 128.6, 126.9, 122.8, 118.2, 113.7, 111.9, 110.3, 108.2, 101.1, 53.8, 45.9; HRMS(ESI)calcd.for C 25 H 26 N 8 O[M+H] + ,454.2230; found,454.2235.

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 synthesis and medical application of pyrrolo-[2,1-f] [1,2,4] triazine mother nucleus compound. The compound belongs to a novel-structure compound. The synthesis method is high in operating safety, mild in reaction condition and suitable for industrial production. The activity and the selectivity of BTK kinase and the in-vitro proliferation activity of a leukemia cell line are test, it is verified that the compound has the selective and irreversible inhibition effect on the BTK kinase, and has the different-degree inhibition effect on leukemia cells. According to measurement, the compound also has the good anti-arthritic activity on a collagen-induced arthritis (rCIA) model. The pyrrolo-[2,1-f] [1,2,4] triazine mother nucleus compound can be used for preparing medicine for treating arthritis and leukemia.

Description

Technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a class of pyrrolo[2,1-f][1,2,4]triazine core compounds and their medical uses. Background technique [0002] Bruton Tyrosine kinase (BTK) is a non-receptor tyrosine kinase that belongs to the Tec family and is mainly expressed in B cells. It is an important factor in the B cell signaling pathway and affects the development of B cells in the body And mature. In the immune system, B cells can recognize antigens, present antigens to T cells, and assist T cell activation; B cells can also produce autoantibodies (RF, CCP) and secrete inflammatory factors (IL-6, IFN, TNF) to accelerate disease process. BTK is a key factor for B cells to exercise immune function. It is extremely important for the differentiation, development, proliferation, and apoptosis of B cells. Inhibiting BTK can effectively block the migration and adhesion of malignant B cells and lead to B cell apoptosis. Theref...

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 Patents(China)
IPC IPC(8): C07D487/04A61P35/02A61P19/02A61P29/00
CPCC07D487/04
Inventor 梁承远贾敏一田丹妮孙涵
Owner NINGBO WESDON POWDER PHARMA COATINGS CO LTD
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