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

Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase

a technology of triazolopyrimidine and thioether triazolopyridine, which is applied in the direction of drug compositions, organic chemistry, cardiovascular disorders, etc., can solve the problem that cardiovascular disease is a major health risk

Inactive Publication Date: 2017-08-31
BRISTOL MYERS SQUIBB CO
View PDF1 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present patent provides compounds that can inhibit the activity of MPO and / or EPX, which are enzymes involved in the inflammation process. The compounds can be used to treat diseases associated with these enzymes, such as atherosclerosis, heart failure, and lung diseases. The compounds can be used alone or in combination with other compounds or agents. Overall, the patent provides a valuable tool to treat inflammation-related diseases.

Problems solved by technology

Cardiovascular disease is a major health risk throughout the industrialized world.

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
  • Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase
  • Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase
  • Thioether triazolopyridine and triazolopyrimidine inhibitors of myeloperoxidase

Examples

Experimental program
Comparison scheme
Effect test

example 1

hio)-3H-[1,2,3]triazolo[4,5-b]pyridin-5-amine

[0315]

[0316]To a mixture of Intermediate 2 (15 mg, 0.088 mmol), and phenylmethanethiol (22 mg, 0.18 mmol) in DMSO (1 mL) was added cesium carbonate (58 mg, 0.18 mmol), and the reaction mixture was stirred at 85° C. for 10 h. The crude mixture was filtered, and the filtrate was diluted with MeOH and purified by preparatory HPLC to obtain the title compound (19 mg, 0.069 mmol, 78% yield) as a yellow solid. MS (ESI) m / z 258.2 (M+H). 1H NMR (500 MHz, CD3OD) δ 8.25 (d, J=7.2 Hz, 2H), 8.21-8.00 (m, 3H), 7.45 (br. s., 1H), 5.34-5.22 (m, 2H).

[0317]The following compounds were prepared in a manner similar to experimental procedures that are described in Example 1 using Intermediate 2 and the appropriate thiol as starting materials:

Ex.No.StructureNameAnalytical Data27-((1-phenylethyl)thio)- 3H-[1,2,3]triazolo[4,5- b]pyridin-5-amineMS (ESI) 272.1 (M + H)+. 1H NMR (500 MHz, CD3OD)) δ 7.55-7.49 (m, 2H), 7.39- 7.33 (m, 2H), 7.31-7.24 (m, 1H), 6.63 (s, ...

example 10a

hlorophenyl)diazenyl)-4-((2,6-difluorobenzyl)thio)pyridine-2,6-diamine

[0319]

[0320]A mixture of Intermediate 2A, (2,6-difluorophenyl)methanethiol (230 mg, 1.4 mmol) and Cs2CO3 (1800 mg, 5.7 mmol) in DMSO (2 mL) was heated for 1 h at 90° C. The mixture was diluted with water, and the mixture was extracted with EtOAc. The combined organics were washed with 1N HCl and brine, dried over MgSO4 and concentrated. The crude was purified by column chromatography to yield Example 10A as an impure brown oil. MS (ESI) m / z 406.2 / 408.2.

example 10b

luorobenzyl)thio)pyridine-2,3,6-triamine

[0321]

[0322]To a solution of 10A (700 mg, 1.7 mmol) in MeOH (50 mL) was added zinc powder (340 mg, 5.2 mmol) followed by glacial acetic acid (0.296 mL, 5.17 mmol). The resulting reaction mixture was heated at 60° C. for 2 h. The reaction mixture was cooled to rt and filtered through a pad of celite. The filtrates were combined and concentrated. The crude product was dissolved in 5.0 mL of 7.0 M NH3 in MeOH and concentrated. The crude product was purified by column chromatography (2.0 M NH3 in MeOH / CH2Cl2, 0-20% gradient) to yield Example 10B (300 mg, 1.1 mmol, 62% yield). MS (ESI) m / z 283.3.

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

PropertyMeasurementUnit
pHaaaaaaaaaa
total volumeaaaaaaaaaa
total volumeaaaaaaaaaa
Login to View More

Abstract

The present invention provides compounds of Formula (I): wherein A, X and Y are as defined in the specification, and compositions comprising any of such novel compounds. These compounds are myeloperoxidase (MPO) inhibitors and / or eosinophil peroxidase (EPX) inhibitors, which may be used as medicaments.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS[0001]This application claims priority from U.S. Provisional Application No. 62 / 048,857 filed Sep. 11, 2014, the disclosures of which are incorporated herein by reference in their entirety.FIELD OF THE INVENTION[0002]The present invention relates to novel thioether triazolopyridine and triazolopyrimidine compounds, which are myeloperoxidase (MPO) inhibitors and / or eosinophil peroxidase (EPX) inhibitors, compositions containing them, and methods of using them, for example, for the treatment of atherosclerosis, heart failure, chronic obstructive pulmonary disease (COPD), and related diseases.BACKGROUND OF THE INVENTION[0003]Cardiovascular disease is a major health risk throughout the industrialized world. Atherosclerosis, the most prevalent of cardiovascular diseases, is the principal cause of heart attack and stroke, and thereby the principal cause of death in the United States. Atherosclerosis is a complex disease involving many cell types and ...

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(United States)
IPC IPC(8): C07D249/16C07D471/04C07D487/04A61K31/437A61K31/7064
CPCC07D249/16A61K31/437C07D471/04C07D487/04A61K31/7064A61P11/00A61P9/00A61P9/04
Inventor VIET, ANDREW QUOCWURTZ, NICHOLAS R.
Owner BRISTOL MYERS SQUIBB CO
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