Phenyl phthalazine derivative, method for the preparation thereof, and pharmaceutical composition comprising the same

Patent metadata

Field	Value
Publication number	US-10947241-B2
Application number	US-201716344080-A
Country	US
Kind code	B2
Filing date	Oct 27, 2017
Priority date	Oct 28, 2016
Publication date	Mar 16, 2021
Grant date	Mar 16, 2021

Abstract

The present invention relates to a compound represented by Chemical Formula 1, or a pharmaceutically acceptable salt thereof. The compound according to the present invention can be usefully used for the prevention or treatment of cardiovascular diseases.

First claim

What is claimed is:

1. A compound represented by the following Chemical Formula 1, or a pharmaceutically acceptable salt thereof:

in Chemical Formula 1,
X is N,
L 1 is a single bond, C 1-4 alkylene, C 2-4 alkenylene, NH, O, or SO 2 ,
L 3 is a single bond,
R 1 is hydrogen, C 1-4 alkyl, C 1-4 alkyl substituted with carboxy group, C 1-4 haloalkyl, C 1-4 alkoxy, C 1-4 haloalkoxy, halogen, cyano, nitro, 4-methylpiperazin-1-carbonyl, carboxy, morpholino, (C 1-4 alkyl)sulfonyl, (piperidinyl)sulfonyl, or (piperazinyl)sulfonyl,
R 3 is hydrogen, or C 1-4 alkyl,
R 4 is hydrogen, or halogen,
n is 1 or 2, and
A-L 2 -R 2 is represented by the following formula 1′:

in Chemical Formula 1′,
Y is N, is a single bond,
Z is CH, or N,
n1 is 1,
n2 is 1 or 2,
L 2 is NH, and
R 2 is C 1-4 alkyl unsubstituted or substituted with amino; C 3-6 cycloalkyl; amino; N(C 1-4 alkyl) 2 ; hydroxy; morpholino; or pyrrolidinyl.

2. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein L 1 is a single bond, —CH 2 —, —CH═CH—, —CH 2 —CH═CH—, NH, O, or SO 2 .

3. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 1 is hydrogen, methyl, ethyl substituted with carboxy group, trifluoromethyl, methoxy, trifluoromethoxy, fluoro, chloro, cyano, nitro, 4-methylpiperazine-1-carbonyl, carboxy, morpholino, methylsulfonyl, (piperidin-1-yl)sulfonyl, or (piperazin-1-yl)sulfonyl.

4. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein R 2 is methyl, ethyl, propyl, isopropyl, butyl, isobutyl, isopentyl, cyclopropyl, cyclobutyl, cyclopentyl, amino, dimethylamino, hydroxyl, morpholino, or pyrrolidinyl.

5. The compound or a pharmaceutically acceptable salt thereof according to claim 1 , wherein the compound represented by the Chemical Formula 1 is any one selected from the group consisting of:
1) 1-(4-(4-chlorophenyl)phthalazin-1-yl)-N-methylpyrrolidin-3-amine hydrochloride,
2) 1-(4-(4-chlorophenyl)phthalazin-1-yl)-N-ethylpyrrolidin-3-amine,
3) (R)-1-(4-(4-chlorophenyl)phthalazin-1-yl)-N-methylpiperidin-3-amine,
4) 1-(7-chloro-4-(4-chlorophenyl)phthalazin-1-yl)-N-methylpyrrolidin-3-amine,
5) 1-(6-chloro-4-(4-chlorophenyl)phthalazin-1-yl)-N-methylpyrrolidin-3-amine,
6) 1-(4-(4-chlorophenyl)-6-fluorophthalazin-1-yl)-N-methylpyrrolidin-3-amine,
7) 1-(4-(4-chlorophenoxy)phthalazin-1-yl)-N-methylpyrrolidin-3-amine,
8) N-(4-chlorophenyl)-4-(3-(methylamino)pyrrolidin-1-yl)phthalazin-1-amine, and
9) 1-(4-(4-chlorobenzyl)phthalazin-1-yl)-N-methylpyrrolidin-3-amine.

6. A pharmaceutical composition for preventing or treating cardiovascular diseases, comprising the compound according to claim 1 or a pharmaceutically acceptable salt thereof.

Assignees

• Seoul Nat Univ Hospital

Inventors

• Yoo Ja Kyung
• Lee Nora
• Lee Chun Ho
• Jung Myunggi
• Kim Hyo-Soo

Classifications

• C07D403/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• A61K31/496

  Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin · CPC title

• C07D405/12

  linked by a chain containing hetero atoms as chain links · CPC title

• C07D237/26

  condensed with carbocyclic rings or ring systems · CPC title

• A61K31/502

  ortho- or peri-condensed with carbocyclic ring systems, e.g. cinnoline, phthalazine · CPC title