Benzamide derivative compound, method for preparing same, and pharmaceutical composition for treating or preventing inflammatory disease containing same as active ingredient

Patent metadata

Field	Value
Publication number	US-12441690-B2
Application number	US-201816764843-A
Country	US
Kind code	B2
Filing date	Nov 16, 2018
Priority date	Nov 16, 2017
Publication date	Oct 14, 2025
Grant date	Oct 14, 2025

Abstract

The present invention relates to a benzamide derivative compound, a method for preparing the same, and a pharmaceutical composition for treating or preventing an inflammatory disease containing the same as an active ingredient. The benzamide derivative compound according to the present invention inhibits the expression of PDE4 and regulates the expression of an inflammatory disease-related substance such as IL-4 (interleukin-4), IL-5 (interleukin-4), IFN-γ (interferon-γ), IL-17 (interluekin-17), IgE (immunoglobulin E), and TNF-α (tumor necrosis factor-α), and thus may be utilized as a pharmaceutical composition for treating or preventing an inflammatory disease.

First claim

What is claimed is:

1. A compound represented by Formula 1 below, an optical isomer thereof or a pharmaceutically acceptable salt thereof:

wherein,
L is single bond or straight or branched C 1 -C 6 alkylene;
R 1 is hydrogen; C 3 -C 8 cycloalkyl; substituted or unsubstituted C 6 -C 12 aryl, wherein the substituted C 6 -C 12 aryl is substituted with one or more substituents selected from the group consisting of halogen, —NH 2 , straight or branched C 1 -C 3 alkyl, and straight or branched C 1 -C 3 alkoxy; substituted or unsubstituted heteroaryl consisting of 6 to 12 atoms containing one or more heteroatoms selected from the group consisting of N and O, wherein the substituted heteroaryl consisting of 6 to 12 atoms is substituted with one or more halogens; or heterocycloalkyl consisting of 6 to 10 atoms containing one or more heteroatoms selected from the group consisting of N and O; and
R 2 is hydrogen or straight or branched C 1 -C 3 alkyl;
R 3 is substituted or unsubstituted C 6 -C 10 aryl, wherein the substituted C 6 -C 10 aryl is substituted with one or more methoxy groups; or substituted or unsubstituted morpholinyl or piperazinyl, wherein the substituted morpholinyl or piperazinyl is substituted with one or more hydroxyl ethyl groups; and
R 4 is C 1 -C 3 haloalkyl,
or
wherein,
L is single bond;
R 1 is C 3 -C 8 cycloalkyl; substituted or unsubstituted C 6 -C 12 aryl, wherein the substituted C 6 -C 12 aryl is substituted with one or more substituents selected from the group consisting of halogen, —NH 2 , straight or branched C 1 -C 3 alkyl, and straight or branched C 1 -C 3 alkoxy; substituted or unsubstituted heteroaryl consisting of 6 to 12 atoms containing one or more heteroatoms selected from the group consisting of N and O, wherein the substituted heteroaryl consisting of 6 to 12 atoms is substituted with one or more halogens; or heterocycloalkyl consisting of 6 to 10 atoms containing one or more heteroatoms selected from the group consisting of N and O; and
R 2 is hydrogen or straight or branched C 1 C 3 alkyl;
R 3 is substituted C 6 -C 10 aryl, wherein the substituted C 6 -C 10 aryl is substituted with one or more methoxy groups; or substituted or unsubstituted morpholinyl or piperazinyl, wherein the substituted morpholinyl or piperazinyl is substituted with one or more hydroxyl ethyl groups; and
R 4 is —SR 5 or SO 2 R 5 , wherein R 5 is straight or branched C 1 -C 6 alkyl,
or
wherein,
L is straight or branched C 1 -C 6 alkylene;
R 1 is substituted or unsubstituted C 6 -C 12 aryl, wherein the substituted C 6 -C 12 aryl is substituted with one or more substituents selected from the group consisting of halogen, —NH 2 , straight or branched C 1 -C 3 alkyl, and straight or branched C 1 -C 3 alkoxy; substituted or unsubstituted heteroaryl consisting of 6 to 12 atoms containing one or more heteroatoms selected from the group consisting of N and O, wherein the substituted heteroaryl consisting of 6 to 12 atoms is substituted with one or more halogens; or heterocycloalkyl consisting of 6 to 10 atoms containing one or more heteroatoms selected from the group consisting of N and O; and
R 2 is hydrogen or straight or branched C 1 -C 3 alkyl;
R 3 is substituted or unsubstituted morpholinyl or piperazinyl, wherein the substituted morpholinyl or piperazinyl is substituted with one or more hydroxyl ethyl groups; and
R 4 is —SR 5 or SO 2 R 5 , wherein R 5 is straight or branched C 1 -C 6 alkyl.

2. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein:
L is single bond or straight or branched C 1 -C 3 alkylene;
R 1 is hydrogen; C 3 -C 6 cycloalkyl; substituted or unsubstituted C 6 -C 10 aryl, wherein the substituted C 6 -C 10 aryl is substituted with one or more substituents selected from the group consisting of fluoro —NH 2 , methoxy and isopropyl; substituted or unsubstituted heteroaryl consisting of 6 to 10 atoms containing one or more heteroatoms selected from the group consisting of N and O, wherein the substituted heteroaryl consisting of 6 to 10 atoms is substituted with one or more chloro; or heterocycloalkyl consisting of 6 to 8 atoms containing one or more heteroatoms selected from the group consisting of N and O;
R 2 is hydrogen or straight or branched C 1 -C 3 alkyl;
R 3 is C 6 -C 10 aryl substituted with one or more methoxy groups; or substituted or unsubstituted morpholinyl or piperazinyl, wherein the substituted morpholinyl or piperazinyl is substituted with one or more hydroxyl ethyl groups; and
R 4 is —CH 2 F, —CHF 2 , —CF 3 , —CH 2 Cl, —CHCl 2 , —CCl 3 , —CH 2 Br, —CHBr 2 , or —CBr 3 , or
L is single bond;
R 1 is C 3 -C 6 cycloalkyl; substituted or unsubstituted C 6 -C 10 aryl, wherein the substituted C 6 -C 10 aryl is substituted with one or more substituents selected from the group consisting of fluoro, —NH 2 , methoxy and isopropyl; substituted or unsubstituted heteroaryl consisting of 6 to 10 atoms containing one or more heteroatoms selected from the group consisting of N and O, wherein the substituted heteroaryl consisting of 6 to 10 atoms is substituted with one or more chloro; or heterocycloalkyl consisting of 6 to 8 atoms containing one or more heteroatoms selected from the group consisting of N and O;
R 2 is hydrogen or straight or branched C 1 -C 3 alkyl;
R 3 is C 6 -C 10 aryl substituted with one or more methoxy groups; or substituted or unsubstituted morpholinyl or piperazinyl, wherein the substituted morpholinyl or piperazinyl is substituted with one or more hydroxyl ethyl groups; and
R 4 is —SR 5 or SO 2 R 5 , wherein R 5 is straight or branched C 1 -C 3 alkyl, or
L is straight or branched C 1 -C 3 alkylene;
R 1 is hydrogen; C 3 -C 6 cycloalkyl; substituted or unsubstituted C 6 -C 10 aryl, wherein the substituted C 6 -C 10 aryl is substituted with one or more substituents selected from the group consisting of fluoro, —NH 2 , methoxy and isopropyl; substituted or unsubstituted heteroaryl consisting of 6 to 10 atoms containing one or more heteroatoms selected from the group consisting of N and O, wherein the substituted heteroaryl consisting of 6 to 10 atoms is substituted with one or more chloro; or heterocycloalkyl consisting of 6 to 8 atoms containing one or more heteroatoms selected from the group consisting of N and O;
R 2 is hydrogen or straight or branched C 1 -C 3 alkyl;
R 3 is substituted or unsubstituted morpholinyl or piperazinyl, wherein the substituted morpholinyl or piperazinyl is substituted with one or more hydroxyl ethyl groups; and
R 4 is —SR 5 or SO 2 R 5 , wherein R 5 is straight or branched C 1 -C 3 alkyl.

3. The compound, the optical isomer thereof or the pharmaceutically acceptable salt thereof according to claim 1 , wherein:
L is single bond, —CH 2 — or —CH 2 CH 2 —;
R 1 is hydrogen, cyclopropyl, morpholinyl, tetrahydropyranyl, indolyl, phenyl or pyridinyl unsubstituted or substituted with one or more chloro; wherein phenyl can be substituted with one or more substituents selected from the group consisting of methoxy, fluoro, isopropyl and —NH 2 ;
R 2 is hydrogen, methyl or ethyl;
R 3 is morpholinyl; phenyl unsubstituted or substituted with one or more methoxy; or piperazinyl unsubstituted or substituted with one or more hydroxy ethyl groups; and
R 4 is —CHF 2 , —CH 2 F, or —CF 3 ,
or
wherein,
L is single bond;
R 1 is cyclopropyl, morpholinyl, tetrahydropyranyl, indolyl, phenyl or pyridinyl unsubstituted or substituted with one or more chloro; wherein phenyl

Assignees

• Seoul Nat Univ R&Db Foundation
• Seoul National Univ R&Dbfoundation

Inventors

• Song Joon Myong

Classifications

• A61K31/505

  Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim · CPC title

• A61K31/506

  not condensed and containing further heterocyclic rings · CPC title

• A61P17/04

  Antipruritics · CPC title

• C07D239/42

  One nitrogen atom (nitro radicals C07D239/30) · CPC title

• C07D239/40

  as doubly bound sulfur atom or as unsubstituted mercapto radical · CPC title