KCNQ potassium ion channel agonist, pharmaceutical composition and application of KCNQ potassium ion channel agonist

A potassium ion channel and agonist technology, applied in the field of pharmacy, can solve the problems of low agonistic activity, insufficient selectivity, and reduced electron cloud density, and achieve the effect of high agonistic activity and high selectivity

Pending Publication Date: 2022-04-22
TAIZHOU UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] In view of the deficiencies in the prior art, the first object of the present invention is to provide a KCNQ potassium ion channel agonist, which is designed to modify and adjust the electron-rich aromatic ring in the middle, so that the electron cloud density can be reduced while maintaining the structure, solving the problem of The existing KCNQ potassium ion channel agonist has low agonist activity and insufficient selectivity for Kv7.2 potassium ion channel, and achieves the purpose of avoiding the intermediate aromatic epoxidation

Method used

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  • KCNQ potassium ion channel agonist, pharmaceutical composition and application of KCNQ potassium ion channel agonist
  • KCNQ potassium ion channel agonist, pharmaceutical composition and application of KCNQ potassium ion channel agonist
  • KCNQ potassium ion channel agonist, pharmaceutical composition and application of KCNQ potassium ion channel agonist

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Embodiment 1: It is a KCNQ potassium ion channel agonist disclosed by the present invention, a compound having a structure shown in the following formula (I) or a pharmaceutically acceptable salt thereof,

[0061]

[0062] Among them, R 1 selected from H, halogen, substituted or unsubstituted phenyl, or substituted or unsubstituted phenylalkyl, the substituents of phenyl and phenylalkyl are each independently selected from halogen or haloalkyl;

[0063] X is selected from S or C;

[0064] R 2 optionally selected from H, alkyl, alkenyl or alkynyl;

[0065] R 3 and R 4 each independently selected from H or alkyl;

[0066] Y is selected from O or S;

[0067] R 5 selected from substituted or unsubstituted alkyl, substituted or unsubstituted cycloalkyl, alkoxy or furyl, the substituent of alkyl selected from alkoxy, dialkylamino or alkoxycarbonyl, cycloalkyl The substituents for are selected from halogen.

Embodiment 2

[0068] Embodiment 2: a KCNQ potassium ion channel agonist disclosed by the present invention, the difference from Example 1 is that R 2 Choose from H, C 1 ~C 3 Alkyl, C 1 ~C 3 Alkenyl or C 1 ~C 3 Alkynyl.

[0069] R 3 and R 4 each independently selected from H or C 1 ~C 6 alkyl.

[0070] R 5 selected from substituted or unsubstituted C 1 ~C 6 Alkyl, substituted or unsubstituted C 3 ~C 6 Cycloalkyl, C 1 ~C 6 Alkoxy or furyl, the substituent of alkyl is selected from C 1 ~C 6 Alkoxy, two (C 1 ~C 4 Alkyl) amino or C 1 ~C 6 Alkoxycarbonyl, cycloalkyl substituents are selected from halogen.

Embodiment 3

[0071] Embodiment 3: It is a KCNQ potassium ion channel agonist disclosed by the present invention. The difference from Example 1 is that the compound has a structure selected from the following formulas (II) to (IV),

[0072]

[0073] Among them, n≥0;

[0074] R 11 and R 12 each independently selected from H, halogen or halomethyl;

[0075] R 2 Choose from H, C 1 ~C 3 Alkyl, C 2 ~C 3 Alkenyl or C 2 ~C 3 Alkynyl;

[0076] R 3 and R 4 each independently selected from H or C 1 ~C 6 alkyl;

[0077] Y is selected from O or S;

[0078] R 5 selected from substituted or unsubstituted C 1 ~C 6 Alkyl, substituted or unsubstituted C 3 ~C 6 Cycloalkyl, C 1 ~C 6 Alkoxy or furyl, the substituent of alkyl is selected from C 1 ~C 6 Alkoxy, two (C 1 ~C 4 Alkyl) amino or C 1 ~C 6 Alkoxycarbonyl, cycloalkyl substituents are selected from halogen.

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Abstract

The invention relates to a KCNQ potassium channel agonist, a pharmaceutical composition and application of the KCNQ potassium channel agonist. The KCNQ potassium ion channel agonist is a compound with a structure as shown in a formula (I) or a pharmaceutically acceptable salt of the compound. The pharmaceutical composition comprises the KCNQ potassium ion channel agonist as an effective component and pharmaceutically acceptable auxiliary materials. The invention also discloses an application of the KCNQ potassium channel agonist or the pharmaceutical composition in preparation of drugs for treating neurological diseases. The KCNQ potassium ion channel agonist disclosed by the invention has a compound with a structure shown in the formula (I) or pharmaceutically acceptable salt thereof, and has the advantages of high agonistic activity, high selectivity for a Kv7.2 potassium ion channel and difficulty in oxidation of an intermediate aromatic ring; the pharmaceutical composition disclosed by the invention has the advantages of high agonistic activity and high selectivity for a Kv7.2 potassium ion channel; after the KCNQ potassium channel agonist or the pharmaceutical composition is applied, the KCNQ potassium channel agonist or the pharmaceutical composition has the advantage of treating neurological diseases.

Description

technical field [0001] The invention relates to the technical field of pharmacy, in particular to a KCNQ potassium ion channel agonist, a pharmaceutical composition and applications thereof. Background technique [0002] Voltage gated potassium channel (Voltage gated potassium channel; Kv) is a transmembrane glycoprotein with potassium ion selective holes on the plasma membrane, composed of α subunit and β subunit, four homologous or heterologous α The subunits constitute functional channels, and the β subunit assists the α subunit to function by regulating the current characteristics or participating in the repolarization process. Each α subunit includes six transmembrane segments (S1-S6), an additional pore loop between S5 and S6, and intracellular N- and C-termini. Among them, the pore ring between S5 and S6 contains highly conserved TXGYG / TXGFG sequence to ensure the selective permeability of potassium ions, and the pore ring of four homologous or heterologous α subunit...

Claims

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Application Information

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IPC IPC(8): C07D209/08C07D277/66A61P25/08A61P25/04A61P9/10A61P25/00A61K31/404A61K31/428
CPCC07D209/08C07D277/66A61P25/08A61P25/04A61P9/10A61P25/00
Inventor 王健邵黎明
Owner TAIZHOU UNIV
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