N,n-disubstituted aminoalkylbiphenyl antagonists of prostaglandin d2 receptors

Abstract

Described herein are compounds that are antagonists of PGD 2 receptors. Also described are pharmaceutical compositions and medicaments that include the compounds described herein that are antagonists of PGD 2 receptors. Also described herein are methods of using such antagonists of PGD 2 receptors, alone and in combination with other compounds, for treating respiratory, cardiovascular, and other PGD 2 -dependent or PGD 2 -mediated conditions or diseases.

What is claimed is: 
     
         1 - 99 . (canceled) 
     
     
         100 . A method for treating a respiratory disease or condition in a mammal comprising administering to the mammal a therapeutically effective amount of an antagonist of DP2, wherein the antagonist is selective for DP2. 
     
     
         101 . The method of  claim 100 , wherein the respiratory disease or condition is asthma, adult respiratory distress syndrome, allergic asthma, non-allergic asthma, acute severe asthma, chronic asthma, clinical asthma, nocturnal asthma, allergen-induced asthma, aspirin-sensitive asthma, exercise-induced asthma, neutrophilic asthma, isocapnic hyperventilation, child-onset asthma, adult-onset asthma, cough-variant asthma, occupational asthma, steroid-resistant asthma, seasonal asthma, seasonal allergic rhinitis, perennial allergic rhinitis, chronic obstructive pulmonary disease, including chronic bronchitis or emphysema, pulmonary hypertension, interstitial lung fibrosis, airway inflammation, cystic fibrosis, or hypoxia. 
     
     
         102 . The method of  claim 100 , wherein the respiratory disease or condition is asthma. 
     
     
         103 . The method of  claim 100 , wherein the respiratory disease or condition is adult respiratory distress syndrome, allergic asthma, non-allergic asthma, acute severe asthma, chronic asthma, clinical asthma, nocturnal asthma, allergen-induced asthma, aspirin-sensitive asthma, exercise-induced asthma, neutrophilic asthma, isocapnic hyperventilation, child-onset asthma, adult-onset asthma, cough-variant asthma, occupational asthma, steroid-resistant asthma, or seasonal asthma. 
     
     
         104 . The method of  claim 100 , wherein the respiratory disease or condition is rhinitis. 
     
     
         105 . The method of  claim 100 , wherein the respiratory disease or condition is allergic rhinitis, non-allergic rhinitis, chronic rhinitis, allergen-induced rhinitis, aspirin-sensitive rhinitis, child-onset rhinitis, adult-onset rhinitis, occupational rhinitis, steroid-resistant rhinitis, seasonal rhinitis, perennial rhinitis, rhinosinusitis, or rhinopolyposis. 
     
     
         106 . The method of  claim 100 , wherein the antagonist of DP2 is administered to the mammal by intravenous injection, oral administration, inhalation, nasal administration, topical administration, ophthalmic administration or otic administration. 
     
     
         107 . The method of  claim 100 , wherein the method further comprises administering to the mammal a second therapeutic agent selected from 5-lipoxygenase-activating protein inhibitors, 5-lipoxygenase inhibitors, CYSLTR1 antagonists, CYSLTR2 antagonists, BLT1 antagonists, BLT2 antagonists, thromboxane antagonists, DP1 receptor antagonists, DP1 receptor agonists, IP receptor agonists, anti-IgE, chemokine receptor antagonists, IL5 antibody, bronchodilators, theophylline, leukotriene receptor antagonists, leukotriene formation inhibitors, decongestants, antihistamines, mucolytics, corticosteroids, glucocorticoids, anticholinergics, antitussives, analgesics, expectorants, and β-2 agonists 
     
     
         108 . A method for treating an allergic disease or condition in a mammal comprising administering to the mammal a therapeutically effective amount of an antagonist of DP2, wherein the antagonist is selective for DP2. 
     
     
         109 . The method of  claim 108 , wherein the allergic disease or condition is allergic rhinitis, asthma, dermatitis, or allergic conjunctivitis. 
     
     
         110 . The method of  claim 108 , wherein the antagonist of DP2 is administered to the mammal by intravenous injection, oral administration, inhalation, nasal administration, topical administration, ophthalmic administration or otic administration. 
     
     
         111 . The method of  claim 108 , wherein the method further comprises administering to the mammal a second therapeutic agent selected from 5-lipoxygenase-activating protein inhibitors, 5-lipoxygenase inhibitors, CYSLTR1 antagonists, CYSLTR2 antagonists, BLT1 antagonists, BLT2 antagonists, thromboxane antagonists, DP1 receptor antagonists, DP1 receptor agonists, IP receptor agonists, anti-IgE, chemokine receptor antagonists, IL5 antibody, bronchodilators, theophylline, leukotriene receptor antagonists, leukotriene formation inhibitors, decongestants, antihistamines, mucolytics, corticosteroids, glucocorticoids, anticholinergics, antitussives, analgesics, expectorants, and 13-2 agonists 
     
     
         112 . A method for treating an inflammatory disease or condition in a mammal comprising administering to the mammal a therapeutically effective amount of an antagonist of DP2, wherein the antagonist is selective for DP2. 
     
     
         113 . The method of  claim 112 , wherein the inflammatory disease or condition is asthma, rhinitis, chronic obstructive pulmonary disease, pulmonary hypertension, or interstitial lung fibrosis. 
     
     
         114 . The method of  claim 112 , wherein the antagonist of DP2 is administered to the mammal by intravenous injection, oral administration, inhalation, nasal administration, topical administration, ophthalmic administration or otic administration. 
     
     
         115 . The method of  claim 112 , wherein the method further comprises administering to the mammal a second therapeutic agent selected from 5-lipoxygenase-activating protein inhibitors, 5-lipoxygenase inhibitors, CYSLTR1 antagonists, CYSLTR2 antagonists, BLT1 antagonists, BLT2 antagonists, thromboxane antagonists, DP1 receptor antagonists, DP1 receptor agonists, IP receptor agonists, anti-IgE, chemokine receptor antagonists, IL5 antibody, bronchodilators, theophylline, leukotriene receptor antagonists, leukotriene formation inhibitors, decongestants, antihistamines, mucolytics, corticosteroids, glucocorticoids, anticholinergics, antitussives, analgesics, expectorants, and β-2 agonists.