Cyclohexylamine derivatives having β2 adrenergic agonist and M3 muscarinic antagonist activities

Patent metadata

Field	Value
Publication number	US-9233108-B2
Application number	US-201214357344-A
Country	US
Kind code	B2
Filing date	Nov 9, 2012
Priority date	Nov 11, 2011
Publication date	Jan 12, 2016
Grant date	Jan 12, 2016

Abstract

The present invention relates to novel compounds having β2 adrenergic agonist and M3 muscarinic antagonist dual activity, to pharmaceutical compositions containing them, to the process for their preparation and to their use in respiratory therapies.

First claim

The invention claimed is:

1. A compound of Formula (I), or a pharmaceutically acceptable salt, N-oxide, solvate, or deuterated derivative thereof:

wherein:
B has formula:

wherein
X together with Y forms —CH═CH—, and
* is a point of attachment of B to the remainder of Formula (I);

R 1 is a hydrogen atom;
R 2 is a methyl group;
R 3 has formula:

wherein
R 4 is a hydroxy group,
R 5 and R 6 are each thienyl groups, and
* is a point of attachment of R 3 to the remainder of Formula (I);

A 1 and A 2 are each independently a C 1-6 alkylene group; and
-G-L 1 - has formula:

wherein
W is chosen from a nitrogen atom or a carbonyl group,
V is chosen from a nitrogen atom or an oxygen atom,
• is a point of attachment with A 1 , and
* is a point of attachment with A 2 .

2. The compound according to claim 1 , wherein the compound is chosen from:
trans-4-[{3-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]propyl}(methyl)amino]-cyclohexyl hydroxy(di-2-thienyl)acetate;
trans-4-[{3-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-2,3-dihydro-1H-benzimidazol-1-yl]propyl}(methyl)amino]cyclohexylhydroxy(di-2-thienyl)acetate;
trans-4-[{3-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-1H-1,2,3-benzotriazol-1-yl]propyl}(methyl)amino]cyclohexylhydroxy(di-2-thienyl)acetate;
trans-4-[{3-[6-(2-{[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}ethyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]propyl}(methyl)amino]cyclohexyl hydroxy(di-2-thienyl)acetate;
trans-4-[{2-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]ethyl}(methyl)amino]cyclohexylhydroxy(di-2-thienyl)acetate;
trans-4-[{4-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzoxazol-3(2H)-yl]butyl}methyl)amino]cyclohexylhydroxy(di-2-thienyl)acetate;
or pharmaceutically acceptable salts thereof.

3. The compound according to claim 1 , wherein the compound is trans-4-[{3-[5-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-1H-1,2,3-benzotriazol-1-yl]propyl}(methyl)amino]cyclohexylhydroxy(di-2-thienyl)acetate or a pharmaceutically acceptable salt thereof.

Assignees

• Almirall Sa

Inventors

• Aiguade Bosch Jose
• Gual Roig Silvia
• Prat Quinones Maria
• Puig Duran Carlos

Classifications

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P43/00

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

• A61P29/00

  Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID] · CPC title

• A61P27/06

  Antiglaucoma agents or miotics · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title