Pharmaceutical product comprising a p38 kinase inhibitor and a second active ingredient

Abstract

The invention provides a pharmaceutical product, kit or composition comprising a first active ingredient which is N-Cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamide or a salt thereof, and a second active ingredient selected from: a non-steroidal Glucocorticoid Receptor (GR Receptor) Agonist; an antioxidant; a β2 adrenoceptor agonist; a CCR1 antagonist; a chemokine antagonist (not CCR1); a corticosteroid; a CRTh2 antagonist; a DPI antagonist; an Histone Deacetylase activator; an IKK2 kinase inhibitor; a COX inhibitor; a lipoxygenase inhibitor; a leukotriene receptor antagonist; a MABA compound; an MPO inhibitor; a muscarinic antagonist; a PDE4 inhibitor; a PPARγ agonist; a protease inhibitor; a Statin; a thromboxane antagonist; a vasodilator; or, an ENAC blocker (Epithelial Sodium-channel blocker); and its use in the treatment of respiratory disease.

1 . A pharmaceutical product comprising, in combination, a first active ingredient which N-Cyclopropyl-3-fluoro-4-methyl-5-[3-[[1-[2-[2-(methylamino)ethoxy]phenyl]cyclopropyl]amino]-2-oxo-1(2H)-pyrazinyl]-benzamide or a salt thereof, and a second active ingredient selected from:
 an Adenosine A2A receptor antagonist;   an anti-infective;   a non-steroidal Glucocorticoid Receptor (GR Receptor) Agonist;   an antioxidant;   a β 2  adrenoceptor agonist;   a CCR1 antagonist;   a chemokine antagonist (not CCR1);   a corticosteroid;   a CRTh2 antagonist;   a DP1 antagonist;   a formyl peptide receptor antagonist;   a Histone Deacetylase activator;   a chloride channel hCLCA1 blocker   an Epithelial sodium channel blocker (ENAC blocker);   an Inter-cellular adhesion molecule 1 blocker (ICAM blocker);   an IKK2 kinase inhibitor;   a JNK kinase inhibitor;   a cyclooxygenase inhibitor (COX inhibitor);   a lipoxygenase inhibitor;   a leukotriene receptor antagonist;   a dual β 2  adrenoceptor agonist/M 3  receptor antagonist (MABA compound);   a MEK-1 kinase inhibitor a myeloperoxidase inhibitor (MPO inhibitor);   a muscarinic antagonist;   a phosphodiesterase PDE4 inhibitor;   a phosphatidylinositol 3 (PI3)-kinase γ inhibitor (PI 3 kinase γ inhibitor)   a peroxisome proliferator activated receptor agonist (PPARγ agonist);   a protease inhibitor;   a retinoic acid receptor modulator (RAR y modulator)   a Statin;   a thromboxane antagonist or   a vasodilator.   
     
     
         2 . A pharmaceutical product as claimed in  claim 1  wherein the second active ingredient is selected from:
 a muscarinic antagonist, 
 a β 2  adrenoceptor agonist; 
 a dual β 2  adrenoceptor agonist/M 3  receptor antagonist (MABA compound); 
 a corticosteroid; 
 a non-steroidal Glucocorticoid Receptor (GR Receptor) Agonist; 
 an IKK2 kinase inhibitor; 
 a phosphodiesterase PDE4 inhibitor or 
 an inhibitor of neutrophil elastase. 
 
     
     
         3 . A pharmaceutical product as claimed in  claim 1 , wherein the second active ingredient is a muscarinic antagonist. 
     
     
         4 . A pharmaceutical product as claimed in  claim 3 , wherein the second active ingredient is a (R)-1-[2-(4-fluoro-phenyl)-ethyl]-3-((S)-2-phenyl-2-piperidin-1-yl-propionyloxy)-1-azonia-bicyclo[2.2.2]octane salt. 
     
     
         5 . A pharmaceutical product as claimed in  claim 3 , wherein the second active ingredient is a ((R)-3-(1-phenyl-cycloheptanecarbonyloxy)-1-(pyridin-2-ylcarbamoylmethyl)-1-azonia-bicyclo[2.2.2]octane salt. 
     
     
         6 . A pharmaceutical product as claimed in  claim 1 , wherein the second active ingredient is a β 2  adrenoceptor agonist. 
     
     
         7 . A pharmaceutical product as claimed in  claim 6 , wherein the second active ingredient is N-[2-(Diethylamino)ethyl]-N-(2-{[2-(4-hydroxy-2-oxo-2,3-dihydro-1,3-benzothiazol-7-yl)ethyl]amino}ethyl)-3-[2-(1-naphthyl)ethoxy]propanamide or a pharmaceutically acceptable salt thereof. 
     
     
         8 . A pharmaceutical product as claimed in  claim 1 , wherein the second active ingredient is a corticosteroid. 
     
     
         9 . A pharmaceutical product as claimed in  claim 1 , wherein the second active ingredient is a non-steroidal Glucocorticoid Receptor (GR Receptor) Agonist. 
     
     
         10 . A pharmaceutical product as claimed in  claim 9 , wherein the second active ingredient is 2,2,2-trifluoro-N-[(1R,2S)-1-[1-(4-fluorophenyl)indazol-5-yl]oxy-1-(3-methoxyphenyl)propan-2-yl]acetamide or a pharmaceutically acceptable salt thereof. 
     
     
         11 . Use of a product according to  claim 1  in therapy. 
     
     
         12 . Use of a product according to  claim 1  in the manufacture of a medicament for the treatment of a respiratory disease. 
     
     
         13 . Use according to  claim 12 , wherein the respiratory disease is chronic obstructive pulmonary disease. 
     
     
         14 . Use according to  claim 12 , wherein the respiratory disease is asthma. 
     
     
         15 . A method of treating a respiratory disease, which method comprises simultaneously, sequentially or separately administering:
 (a) a (therapeutically effective) dose of a first active ingredient which is as defined in  claim 1 ;   (b) a (therapeutically effective) dose of a second active ingredient which is as defined in  claim 1 ;   to a patient in need thereof.