Salts of 2-amino-1-hydroxyethyl-8-hydroxyquinolin-2(1H)-one derivatives having both muscarinic receptor antagonist and β2 adrenergic receptor agonist activities

Patent metadata

Field	Value
Publication number	US-9579316-B2
Application number	US-201414906991-A
Country	US
Kind code	B2
Filing date	Jul 24, 2014
Priority date	Jul 25, 2013
Publication date	Feb 28, 2017
Grant date	Feb 28, 2017

Abstract

The present invention is directed to crystalline addition salts of (i) 8-hydroxyquinolin-2(1H)-one derivatives and (ii) a dicarboxylic acid or a sulfimide, or a pharmaceutically acceptable solvates thereof.

First claim

The invention claimed is:

1. A pharmaceutically acceptable crystalline addition salt chosen from:
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] cyclohexyl hydroxy(di-2-thienyl)acetate saccharinate,
trans-4-[{3-[6-({[(2R)-2-hydroxy-2-(8-hydroxy-2-oxo-1,2-dihydroquinolin-5-yl)ethyl]amino}methyl)-2-oxo-1,3-benzothiazol-3(2H)-yl]propyl}(methyl)-amino]cyclohexyl hydroxy(di-2-thienyl)acetate fumarate,
or a pharmaceutically acceptable solvate thereof.

2. A pharmaceutical composition comprising a therapeutically effective amount of the salt according to claim 1 and a pharmaceutically acceptable carrier.

3. The pharmaceutical composition according to claim 2 , wherein the composition is formulated for administration by inhalation as a dry powder.

4. The pharmaceutical composition according to claim 2 further comprising a therapeutically effective amount of at least one additional therapeutic agent.

5. The pharmaceutical composition according to claim 4 , wherein the at least one additional therapeutic agent is chosen from:
(a) corticosteroids, or glucocorticoids,
(b) antihistamines,
(c) chemokine receptor antagonists,
(e) CRTH 2 antagonists,
(f) leukotriene receptor antagonists,
(g) JAK inhibitors,
(h) Syk inhibitors,
(i) phosdiesterase IV inhibitors,
(j) p38 Inhibitors,
(k) PKC inhibitors,
(l) 5-lipoxygenase activating protein inhibitors,
(m) 5-lipoxygenase inhibitors,
(n) CYSLTR1 antagonists,
(o) CYSLTR2 antagonists,
(p) BLT1 antagonists,
(q) BLT2 antagonists,
(r) thromboxane A2 antagonists,
(s) DP1 receptor antagonists,
(t) DP1 receptor agonists,
(u) IP receptor agonists,
(v) Anti-IgE,
(w) IL5 antibody,
(x) leukotriene formation inhibitors,
(y) decongestants,
(z) mucolytics,
(aa) antitussives,
(bb) analgesics, and
(cc) expectorants.

6. A combination comprising a salt according to claim 1 and at least one additional therapeutic agent chosen from:
(a) corticosteroids, or glucocorticoids,
(b) antihistamines,
(c) chemokine receptor antagonists,
(e) CRTH 2 antagonists,
(f) leukotriene receptor antagonists,
(g) JAK inhibitors,
(h) Syk inhibitors,
(i) phosdiesterase IV inhibitors,
(j) p38 Inhibitors,
(k) PKC inhibitors,
(l) 5-lipoxygenase activating protein inhibitors,
(m) 5-lipoxygenase inhibitors,
(n) CYSLTR1 antagonists,
(o) CYSLTR2 antagonists,
(p) BLT1 antagonists,
(q) BLT2 antagonists,
(r) thromboxane A2 antagonists,
(s) DP1 receptor antagonists,
(t) DP1 receptor agonists,
(u) IP receptor agonists,
(v) Anti-IgE,
(w) IL5 antibody,
(x) leukotriene formation inhibitors,
(y) decongestants,
(z) mucolytics,
(aa) antitussives,
(bb) analgesics, and
(cc) expectorants.

7. A method for treating a subject afflicted with a pathological condition or disease associated with β2 adrenergic receptor agonist and M3 muscarinic receptor antagonist activity, wherein the pathological condition or disease is chosen from asthma or chronic obstructive pulmonary disease, comprising administering to the subject a therapeutically effective amount of the salt according to claim 1 .

8. A method for treating a subject afflicted with a pathological condition or disease associated with β2 adrenergic receptor agonist and M3 muscarinic receptor antagonist activity, wherein the pathological condition or disease is chosen from asthma or chronic obstructive pulmonary disease, comprising administering to the subject the pharmaceutical composition according to claim 2 .

9. A method for treating a subject afflicted with a pathological condition or disease associated with β2 adrenergic receptor agonist and M3 muscarinic receptor antagonist activity, wherein the pathological condition or disease is chosen from asthma or chronic obstructive pulmonary disease, comprising administering to the subject the combination according to claim 6 .

Assignees

• Almirall Sa

Inventors

• Julia Jane Montserrat
• Carrera Carrera Francesc
• Prat Quiñones Maria
• Puig Duran Carlos
• Pajuelo Lorenzo Francesca
• Perez Andres Juan Antonio

Classifications

• A61P11/08

  Bronchodilators · CPC title

• A61P11/00

  Drugs for disorders of the respiratory system · CPC title

• A61P11/06

  Antiasthmatics · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• A61K31/4709 Primary

  Non-condensed quinolines and containing further heterocyclic rings · CPC title