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

Diarylamine derivatives as calcium channel blockers

A technology of diphenyl and diphenylamino, which is used in the field of compounds for the treatment of calcium channel function-related diseases, and can solve the problem of non-specificity of N-type channels

Inactive Publication Date: 2007-07-11
NEUROMED TECH
View PDF15 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, lomerizine is not specific for N-type channels

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
  • Diarylamine derivatives as calcium channel blockers
  • Diarylamine derivatives as calcium channel blockers
  • Diarylamine derivatives as calcium channel blockers

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0088] Synthesis of 1-{4-[(4-chloro-phenyl)-phenyl-methyl]-piperazin-1-yl}-2-diphenylaminoethanone

[0089]

[0090] A. Synthesis of (4-chloro-phenyl)-phenyl-methanol

[0091]

[0092] A solution of 4-chlorobenzaldehyde (1.03 g, 7.34 mmol) in anhydrous ether (10 mL) was added slowly to phenylmagnesium bromide (2.3 mL, 6.98 mmol, 3.0 M in ether) under nitrogen. The mixture was heated to reflux for 1 hour, then cooled to 0°C and hydrolyzed with 1N HCl (40ml). The aqueous phase was extracted with ether (3X), and MgSO 4 The combined organic layers were dried. The crude product was purified using hexane:ethyl acetate (5:1) as eluent to yield 1.5 g of pure product.

[0093] B. Synthesis of 1-chloro-4-(chloro-phenyl-methyl)-benzene

[0094]

[0095] SOCl 2 (8.25ml, 110mmol) and anhydrous CaCl 2 (2g) was added to a solution of (4-chloro-phenyl)-phenyl-methanol (2.41g, 11.06mmol) in anhydrous benzene (20ml). The mixture was heated to reflux for 2 hours, then coole...

Embodiment 2

[0102] Synthesis of 2-diphenylamino-1-[4-(phenyl-pyridin-4-yl-methyl)-piperazin-1-yl]-ethanone

[0103]

[0104] Diphenylglycine (0.51 g, 2.29 mmol) was added to 1-(phenyl-pyridin-4-yl-methyl)-piperazine (0.58 g, 2.29 mmol) in anhydrous CH under nitrogen. 2 Cl 2 (40ml) solution. EDC (0.878 g, 4.58 mmol) and DMAP (cat) were added to the reaction and the reaction mixture was stirred at room temperature overnight under nitrogen. The reaction was then concentrated under reduced pressure. The residue was dissolved in ethyl acetate:water (10:1) (150ml). The organic phase was washed with water (30ml, 2x) and 10% NaOH (30ml), washed with MgSO 4 Dry and evaporate to dryness. The resulting residue was purified by column chromatography with hexane:ethyl acetate (1:1) to give the desired product in 79% yield.

Embodiment 3

[0106] Synthesis of 2-(4-Benzhydryl-piperazin-1-yl)-N,N-diphenyl-acetamide

[0107]

[0108] 2-Bromo-N,N-diphenylacetamide (0.68g, 2.37mmol) and NaHCO 3 (0.4g, 4.74mmol) was added diphenylmethylpiperazine (0.6g, 2.37mmol) in anhydrous CH 3 CN (20ml) solution. The reaction mixture was refluxed overnight. After cooling, the solvent was evaporated, the residue was dissolved in water (15ml) and washed with CHCl 3 Extraction (3 x 50ml). with MgSO 4 The organic layer was dried and evaporated to dryness. The resulting residue was purified by column chromatography with hexane:ethyl acetate (2:1) to give the desired product in 84% yield.

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

N-diarylaminoalkyl-substituted piperazine / 4-aminopiperidine compounds of formula (1) are disclosed, wherein each of A and B is independently a 6-membered aromatic or nonaromatic, carbocyclic or heterocyclic moiety or is an aminoalkyl and wherein one and only one of A and B may be H or alkyl (1-8C) or wherein A and B together form an optionally substituted 6-membered aromatic of nonaromatic, carbocyclic or heterocyclic moiety; R<1> is H or alkyl (1-8C), Z is N or CHNR<2> wherein R<2> is H or alkyl (1-8C), X is straight chain alkylene (1-4C) wherein optionally at least one carbon adjacent to a nitrogen is in the form of C=0; each R<3> is an independent substituent; n=0-2; Ar is a six-membered aromatic or heteroaromatic ring; wherein each cyclic moiety included in A or B each Ar moiety in formula (1) may be substituted by one or more substituents. These compounds and salts or conjugated thereof are able to block N-type and T-type calcium channels and are useful for treating conditions mediated by calcium ion channel activity such as chronic pain.

Description

[0001] related application [0002] This application claims priority to U.S. Application Serial No. 10 / 928,564, filed August 27, 2004, which claims priority to U.S. Application Serial No. 10 / 821,584, filed April 9, 2004, which is incorporated herein in its entirety refer to. technical field [0003] The present invention relates to compounds for treating diseases related to calcium channel function. More particularly, the present invention relates to compounds of diarylamine derivatives containing substituted or unsubstituted 6-membered heterocyclic moieties which are useful in the treatment of diseases such as stroke and pain. Background technique [0004] Calcium entry into cells through voltage-gated calcium channels mediates a variety of cellular and physiological responses, including excitation-contraction coupling, hormone secretion, and gene expression (Miller, 1987; Augustine et al., 1987). In neurons, calcium channels directly affect membrane potential and lead to...

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): C07D405/06C07D401/06C07D295/185C07D295/15C07D241/04C07D241/08C07D211/56C07D211/58A61K31/495A61K31/496A61K31/4468A61P25/04
CPCC07D241/04A61P25/04
Inventor H·帕茹汉斯Y·丁T·P·斯诺切
Owner NEUROMED TECH
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