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

Benzonitrile derivatives as kinase inhibitors

A technology of compounds, mixtures, applied in techniques and procedures, capable of solving problems such as increased kinase expression, high protein kinase activity, increased kinase activity, etc.

Active Publication Date: 2014-07-16
MERCK PATENT GMBH
View PDF10 Cites 15 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Aberrant activity involves: (1) expression in cells that do not normally express these protein kinases; (2) increased kinase expression, which leads to undesired cell proliferation such as cancer; (3) increased kinase activity, which leads to undesired Proliferation of cells such as cancer and / or lead to excessive activity of the corresponding protein kinase

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
  • Benzonitrile derivatives as kinase inhibitors
  • Benzonitrile derivatives as kinase inhibitors
  • Benzonitrile derivatives as kinase inhibitors

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 105-117

[0766] Analytical method:

[0767] LCMS analysis:

[0768] Method A: A-0.1% TFA in H 2 O, B - 0.1% TFA in CAN: flow rate 2.0 ml / min.

[0769] Column: XBridge C8 (50 x 4.6mm, 3.5 μ)

[0770] Method B: A-10mM NH 4 HCO 3 , B: ACN; flow rate: 1.0 ml / min

[0771] Column: XBridge C8 (50x4.6mm, 3.5μ),

[0772] 1 H NMR:

[0773] Bruker 400 MHz

[0774] HPLC:

[0775] Method A:

[0776] Method: A-0.1% TFA in H 2 O, B-0.1% TFA in ACN: Flow rate – 2.0 ml / min.

[0777] Column: XBridge C8 (50 x 4.6 mm, 3.5 μ).

[0778] Synthesis of 5-bromo-2-cyclopropylmethoxybenzonitrile

[0779]

[0780] Sodium hydride, 60% suspended in oil (3.6 g, 0.09 mol) was added to a solution of cyclopropylmethanol (6.49 g, 0.09 mol) in dry DMF (200 ml) at 0 °C under nitrogen middle. After 30 min, 5-bromo-2-fluorobenzonitrile (12.0 g, 0.06 mol) in dry DMF (50 ml) was added at 0 °C and the reaction was stirred at 50 °C for 16 h. Ice water (200 ml) was added to the reaction mixture and extracted w...

Embodiment A

[0939] Example A: Injection Vials

[0940] A solution of 100 g of the active ingredient according to the invention and 5 g of disodium hydrogen phosphate in 3 liters of double distilled water is adjusted to pH 6.5 using 2 N hydrochloric acid, sterile filtered, filled into injection vials and lyophilized under sterile conditions And sealed under sterile conditions. Each injection vial contains 5 mg of active ingredient.

Embodiment B

[0941] Embodiment B: Suppository

[0942] A mixture of 20 g of active ingredient according to the invention with 100 g of soy lecithin and 1400 g of cocoa butter is melted, poured into molds and allowed to cool. Each suppository contains 20 mg of active ingredient.

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 compounds of the formula (I), wherein R1, R2, X and Y have the meaning specified in claim 1, are inhibitors of TBK1 and IotaKappaKappaepsilon, and can be used, inter alia, for the treatment of cancer and inflammatory diseases.

Description

Background technique [0001] The object of the present invention was to find novel compounds having valuable properties, in particular those which can be used for the preparation of medicaments. [0002] The present invention relates to benzonitrile compounds capable of inhibiting one or more kinases. The compound is used in the treatment of a large number of diseases including cancer, septic shock, primary open angle glaucoma (POAG), hyperplasia, rheumatoid arthritis, psoriasis, atherosclerosis, retinopathy , osteoarthritis, endometriosis, chronic inflammatory and / or neurodegenerative diseases such as Alzheimer's disease. [0003] The present invention relates to compounds and uses of compounds that play a role in inhibiting, modulating and / or modulating the signal transduction of receptor kinases, as well as pharmaceutical compositions containing these compounds and the use of these compounds for treating kinase-induced diseases. [0004] Because protein kinases regulate al...

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): C07D401/12C07D401/14C07D405/14C07D413/14C07D417/14C07D471/04C07D491/10A61K31/506A61K31/4433
CPCC07D213/74C07D401/12C07D401/14C07D403/12C07D405/14C07D413/14C07D417/14C07D471/04C07D491/107C07D491/10A61K31/4439A61K31/444A61K31/4545A61K31/497A61K31/501A61K31/506A61K31/5377A61P1/00A61P11/00A61P15/00A61P17/02A61P17/06A61P19/00A61P19/02A61P21/00A61P25/00A61P25/28A61P27/00A61P27/02A61P27/06A61P29/00A61P3/00A61P3/04A61P31/00A61P35/00A61P37/02A61P37/06A61P43/00A61P5/50A61P7/00A61P9/00A61P9/10A61P3/10A61K45/06
Inventor G.赫尔策曼D.多施H-M.埃根魏勒
Owner MERCK PATENT GMBH
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