Lactate dehydrogenase inhibitor and antiepileptic drug containing the same

Patent metadata

Field	Value
Publication number	US-10350192-B2
Application number	US-201615549288-A
Country	US
Kind code	B2
Filing date	Feb 9, 2016
Priority date	Feb 9, 2015
Publication date	Jul 16, 2019
Grant date	Jul 16, 2019

Abstract

The invention provides a lactate dehydrogenase inhibitor that makes it possible to suppress refractory epilepsy in which conventional antiepileptic drugs are ineffective, and an antiepileptic drug containing said inhibitor. The lactate dehydrogenase inhibitor of the invention contains a compound represented by formula (III); i.e., isosafrole or a compound having isosafrole as a scaffold, and the antiepileptic drug of the invention has these compounds as an active ingredient.

First claim

The invention claimed is:

1. A drug comprising a compound represented by formula (III) as an active ingredient:

wherein
R a represents a hydrogen atom, a halogen atom or alkoxy optionally substituted with halogen atoms;
R b represents a hydrogen atom, a halogen atom, or alkoxy optionally substituted with halogen atoms or nitro;
R c represents a hydrogen atom or carboxyl;
R d represents a hydrogen atom or —X 11 —R 11 ;
X 11 represents alkylene, —NH—CO—, —CH 2 —NR 12 —CO— or —S—;
R 11 represents aryl optionally having substituents, carboxyl, alkyl optionally substituted with halogen atoms, or hydroxyalkyl;
R 12 represents hydroxyalkyl;

for R e , R f and R g :
(a) R e and R f together represent ═O, and R g represents any of the following structures:

or
(b) R e and R f together represent ═O, and R g represents —NHR 34 , where R 34 represents any of the following structures:

and
R h represents a hydrogen atom or a halogen atom.

2. A method for inhibiting a lactate dehydrogenase comprising contacting the lactate dehydrogenase with a compound represented by formula (III):

wherein
R a represents a hydrogen atom, a halogen atom or alkoxy optionally substituted with halogen atoms;
R b represents a hydrogen atom, a halogen atom, or alkoxy optionally substituted with halogen atoms or nitro;
R c represents a hydrogen atom or carboxyl;
R d represents a hydrogen atom or —X 11 —R 11 ;
X 11 represents alkylene, —NH—CO—, —CH 2 —NR 12 —CO— or —S—;
R 11 represents aryl optionally having substituents, carboxyl, alkyl optionally substituted with halogen atoms, or hydroxyalkyl;
R 12 represents hydroxyalkyl;

for R e , R f and R g :
(a) R e and R f together represent ═O, and R g represents any of the following structures:

or
(b) R e and R f together represent ═O, and R g represents —NHR 34 , where R 34 represents any of the following structures:

and
R h represents a hydrogen atom or a halogen atom.

3. A method for treating epilepsy comprising administrating an effective amount of a compound represented by formula (III) to a subject of epilepsy:

wherein
R a represents a hydrogen atom, a halogen atom or alkoxy optionally substituted with halogen atoms;
R b represents a hydrogen atom, a halogen atom, or alkoxy optionally substituted with halogen atoms or nitro;
R c represents a hydrogen atom or carboxyl;
R d represents a hydrogen atom or —X 11 —R 11 ;
X 11 represents alkylene, —NH—CO—, —CH 2 —NR 12 —CO— or —S—;
R 11 represents aryl optionally having substituents, carboxyl, alkyl optionally substituted with halogen atoms, or hydroxyalkyl;
R 12 represents hydroxyalkyl;

for R e , R f and R g :
(a) R e and R f together represent ═O, and R g represents any of the following structures:

or
(b) R e and R f together represent ═O, and R g represents —NHR 34 , where R 34 represents any of the following structures:

and
R h represents a hydrogen atom or a halogen atom.

Assignees

• Nat Univ Corporation Okayama Univ

Inventors

• Inoue Tsuyoshi
• Sada Nagisa

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P25/08

  Antiepileptics; Anticonvulsants · CPC title

• C07D495/04

  Ortho-condensed systems · CPC title

• C07D491/06

  Peri-condensed systems · CPC title

• C07D487/08

  Bridged systems · CPC title