Sphinogosine-1 -phosphate receptor modulators for treatment of cardiopulmonary disorders

Patent metadata

Field	Value
Publication number	US-11034691-B2
Application number	US-201916437007-A
Country	US
Kind code	B2
Filing date	Jun 11, 2019
Priority date	Sep 29, 2014
Publication date	Jun 15, 2021
Grant date	Jun 15, 2021

Abstract

The invention provides compounds effective as sphingosine-1-phosphate receptor modulators for treatment of cardiopulmonary diseases, such as hypertension (including malignant hypertension), angina, myocardial infarction, cardiac arrhythmias, congestive heart failure, coronary heart disease, atherosclerosis, angina pectoris, dysrhythmias, cardiomyothopy (including hypertropic cardiomyothopy), heart failure, cardiac arrest, bronchitis, asthma, chronic obstructive pulmonary disease, cystic fibrosis, croup, emphysema, pleurisy, pulmonary fibrosis, pneumonia, pulmonary embolus, pulmonary hypertension, mesothelioma, ventricular conduction abnormalities, complete heart block, adult respiratory distress syndrome, sepsis syndrome, idiopathic pulmonary fibrosis, scleroderma, systemic sclerosis, retroperitoneal fibrosis, prevention of keloid formation, or cirrhosis.

First claim

What is claimed is:

1. A method for the treatment of a patient afflicted with a disease selected from the group consisting of cardiopulmonary disease, sepsis, and systemic sclerosis, comprising administering to the patient a compound of formula (I) or a pharmaceutically acceptable salt thereof:

wherein
Ar 1 is a phenyl optionally mono- or multi-substituted with up to three substituents selected from the group consisting of (C1-C4)alkyl, halo, halo(C1-C4)alkyl, OH, and (C1-C4)alkoxy;
Ar 2 is phenyl or pyridyl, wherein Ar 2 is optionally substituted with up to three substituents selected from the group consisting of (C 1 -C 4 )alkyl, monohydroxy(C 1 -C 4 )alkoxy, halo, cyano, (C 1 -C 4 )alkoxy, (C 1 -C 6 )alkoxycarbonyl(CH 2 ) 0-2 , halo(C 1 -C 4 )alkyl, OH, monohydroxy(C 1 -C 4 )alkyl, NR 2 C(═O)(CH 2 ) 0-2 O(CH 2 ) 0-2 , NR 2 C(═O)(CH 2 ) 0-2 , (C 1 -C 4 )C(═O)N(R), (5- to 10-membered)heterocyclyl, (5- to 10-membered) heteroaryl;
Ar 3 is pyridyl optionally substituted with up to three substituents selected from the group consisting of (C 1 -C 4 )alkyl, (C 2 -C 4 )alkenyl, halo, halo(C 1 -C 4 )alkyl, OH, (C 1 -C 4 )alkoxy, (C 1 -C 6 )alkoxycarbonyl(CH 2 ) 0-2 , carboxy(CH 2 ) 0-2 , monohydroxy(C 1 -C 4 )alkyl, NR 2 (CH 2 ) 0-2 , (C 3 -C 10 )cycloalkyl;
R′ is H,
X is N(R) and L is C(═O); and
R is H or (C 1 -C 4 )alkyl.

2. The method of claim 1 , wherein the compound is a compound of formula (IB) or a pharmaceutically acceptable salt thereof:

wherein Ar 1 and Ar 2 are phenyl.

3. The method of claim 1 , herein the compound of formula (I) is selected from the following table:

52595

52331

52332

52394 IB

52396 IB

52397 IB

52398 IB

52399 IB

52433 IB

52434 IB

52435 IB

52442 IB

52458 IB

52459 IB

52460 IB

52464 IB

52474 IB

52475 IB

Assignees

• Scripps Research Inst

Inventors

• Roberts Edward
• Rosen Hugh
• Urbano Mariangela
• Guerrero Miguel

Classifications

• C09B55/005

  Disazomethine dyes · CPC title

• C07D213/75

  Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates · CPC title

• C07D271/10

  1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles · CPC title

• C09B55/002

  Monoazomethine dyes · CPC title

• C09B55/007 Primary

  containing only carbocyclic rings · CPC title