Permanently charged sodium and calcium channel blockers as anti-inflammatory agents

Abstract

The invention provides compounds, compositions, methods, and kits for the treatment of neurogenic inflammation.

What is claimed is: 
     
         1 - 46 . (canceled) 
     
     
         47 . A quaternary amine derivative of compound 51: 
       
         
           
           
               
               
           
         
       
       or salt thereof. 
     
     
         48 . A pharmaceutical composition comprising the compound of  claim 47  and a pharmaceutically acceptable excipient. 
     
     
         49 . A method of treating a neurogenic inflammatory disorder in a human patient, the method comprising administering a therapeutically effective amount of the compound of  claim 47  to the patient. 
     
     
         50 . The method of  claim 49 , wherein the neurogenic inflammatory disorder is selected from asthma, rhinitis, conjunctivitis, arthritis, colitis, contact dermatitis, pancreatitis, chronic cough, diabetes, rheumatic disease, eczema, cystitis, gastritis, urethritis, migraine headache, psoriasis, sinusitis, chronic rhinosinusitis, traumatic brain injury, sepsis, polymicrobial sepsis, tendinopathy, chronic urticaria, rosacea, sunburn, inhaled tear gases, acute lung injury, inhalation of irritants, inhalation of pollutants, and exposure to chemical warfare agents. 
     
     
         51 . A kit comprising the compound of  claim 47  and instructions for administering the compound to a patient to treat neurogenic inflammation. 
     
     
         52 . A quaternary amine derivative of compound 70: 
       
         
           
           
               
               
           
         
       
       or salt thereof. 
     
     
         53 . A pharmaceutical composition comprising the compound of  claim 52  and a pharmaceutically acceptable excipient. 
     
     
         54 . A method of treating a neurogenic inflammatory disorder in a human patient, the method comprising administering a therapeutically effective amount of the compound of  claim 52  to the patient. 
     
     
         55 . The method of  claim 54 , wherein the neurogenic inflammatory disorder is selected from asthma, rhinitis, conjunctivitis, arthritis, colitis, contact dermatitis, pancreatitis, chronic cough, diabetes, rheumatic disease, eczema, cystitis, gastritis, urethritis, migraine headache, psoriasis, sinusitis, chronic rhinosinusitis, traumatic brain injury, sepsis, polymicrobial sepsis, tendinopathy, chronic urticaria, rosacea, sunburn, inhaled tear gases, acute lung injury, inhalation of irritants, inhalation of pollutants, and exposure to chemical warfare agents. 
     
     
         56 . A kit comprising the compound of  claim 52  and instructions for administering the compound to a patient to treat neurogenic inflammation. 
     
     
         57 . A quarternary amine derivative of compound 86: 
       
         
           
           
               
               
           
         
       
       or salt thereof. 
     
     
         58 . A pharmaceutical composition comprising the compound of  claim 57  and a pharmaceutically acceptable excipient. 
     
     
         59 . A method of treating a neurogenic inflammatory disorder in a human patient, the method comprising administering a therapeutically effective amount of the compound of  claim 57  to the patient. 
     
     
         60 . The method of  claim 59 , wherein the neurogenic inflammatory disorder is selected from asthma, rhinitis, conjunctivitis, arthritis, colitis, contact dermatitis, pancreatitis, chronic cough, diabetes, rheumatic disease, eczema, cystitis, gastritis, urethritis, migraine headache, psoriasis, sinusitis, chronic rhinosinusitis, traumatic brain injury, sepsis, polymicrobial sepsis, tendinopathy, chronic urticaria, rosacea, sunburn, inhaled tear gases, acute lung injury, inhalation of irritants, inhalation of pollutants, and exposure to chemical warfare agents. 
     
     
         61 . A kit comprising the compound of  claim 57  and instructions for administering the compound to a patient to treat neurogenic inflammation. 
     
     
         62 . A quarternary amine derivative of compound 95: 
       
         
           
           
               
               
           
         
       
       or salt thereof. 
     
     
         63 . A pharmaceutical composition comprising the compound of  claim 62  and a pharmaceutically acceptable excipient. 
     
     
         64 . A method of treating a neurogenic inflammatory disorder in a human patient, the method comprising administering a therapeutically effective amount of the compound of  claim 62  to the patient. 
     
     
         65 . The method of  claim 64 , wherein the neurogenic inflammatory disorder is selected from asthma, rhinitis, conjunctivitis, arthritis, colitis, contact dermatitis, pancreatitis, chronic cough, diabetes, rheumatic disease, eczema, cystitis, gastritis, urethritis, migraine headache, psoriasis, sinusitis, chronic rhinosinusitis, traumatic brain injury, sepsis, polymicrobial sepsis, tendinopathy, chronic urticaria, rosacea, sunburn, inhaled tear gases, acute lung injury, inhalation of irritants, inhalation of pollutants, and exposure to chemical warfare agents. 
     
     
         66 . A kit comprising the compound of  claim 62  and instructions for administering the compound to a patient to treat neurogenic inflammation.