AMIDE DERIVATIVES AS Nav1.7 and Nav1.8 BLOCKERS

一种化合物、烷基的技术，应用在酰胺衍生物领域，能够解决不完整疗效、低效力等问题，达到改善副作用特性的效果

Active Publication Date: 2019-12-24
RAQUALIA PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] In the clinic, voltage-gated sodium channel blockers (eg, lidocaine, halothane) have been used in pain management, however their utility is often due to incomplete efficacy at low potency and Limited by undesired side effects that are non-subtype selective, especially for Nav1.5 (eg, arrhythmias)

Method used

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  • AMIDE DERIVATIVES AS Nav1.7 and Nav1.8 BLOCKERS
  • AMIDE DERIVATIVES AS Nav1.7 and Nav1.8 BLOCKERS
  • AMIDE DERIVATIVES AS Nav1.7 and Nav1.8 BLOCKERS

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0940] 2-(Cyclopropanecarboxamido)-N-(2-(4-(trifluoromethyl)phenoxy)propyl)isonicotinamide

[0941] To 2-(4-(trifluoromethyl)phenoxy)propyl-1-amine (15mg, 0.068mmol, amine 1), 2-(cyclopropanecarboxamido)isonicotinic acid (14mg, 0.068mmol, To a mixture of carboxylic acid 2) and N,N-diisopropylethylamine (0.047 mL, 0.27 mmol) in DMF (1 mL) was added HBTU (39 mg, 0.10 mmol) at room temperature. After stirring at 60°C for 2 hours, the mixture was diluted with EtOAc (6 mL), washed with water, and dried over sodium sulfate. The organic layer was purified by NH-silica gel column chromatography and eluted with EtOAc, followed by preparative LC-MS to obtain 8.6 mg of the title compound.

[0942] For the other examples, prepared according to methods similar to those described in Example 1, using appropriate amines and carboxylic acids (see Table 2). The reactants are commercially available materials or can be obtained by conventional methods known to those skilled in the art, otherwis...

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PUM

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Abstract

The present invention relates to amide derivatives which have blocking activities of voltage gated sodium channels as the Nav1.7 and Nav1.8 channels, and which are useful in the treatment or prevention of disorders and diseases in which voltage gated sodium channels are involved. The invention also relates to pharmaceutical compositions comprising these compounds and the use of these compounds andcompositions in the prevention or treatment of such diseases in which voltage gated sodium channels are involved.

Description

technical field [0001] The present invention relates to an amide derivative as a sodium channel blocker, which can be used in various therapeutic applications, especially in the treatment of pain. Background technique [0002] The amide derivatives of the present invention are sodium channel blockers and are used in various treatments, especially in the treatment of pain. More specifically, the amide derivatives of the present invention are modulators of Nav1.7 and Nav1.8 channels. In the discussion that follows, the invention is illustrated by reference to inhibition of Nav1.7 and Nav1.8 channels. These showed significantly higher affinities for Nav1.7 and Nav1.8 channels than those for Nav1.5 channels. Compared with Nav1.5 channel, the amide derivative of the present invention shows good selectivity to Nav1.7 and Nav1.8 channels. [0003] Voltage-gated sodium channels (VGSCs, Nav1.x) play a key role in the initiation and conduction of action potentials in excitable tiss...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D213/81A61K31/444A61K31/506A61P1/00A61P1/18A61P19/02A61P25/08A61P25/22A61P25/24A61P25/28A61P29/00C07D239/42C07D401/12
CPCC07D213/81C07D401/12C07D239/42A61P1/00A61P25/24A61P25/22A61P25/28A61P29/00A61P1/18A61P19/02A61P25/08A61K45/06A61K31/44A61K31/444C07D239/28A61K31/4725A61K31/505A61K31/506A61K31/4709A61P1/04A61P9/02A61P9/06A61P9/10A61P21/00A61P25/02A61P25/04A61P25/06
Inventor 山岸龙也森田干雄肉户祐二山口龙一我谢德一
Owner RAQUALIA PHARMA INC
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