Methods for treating inflammation and hypertension with gamma-ketoaldehyde skavengers

Abstract

A method of treating at least one of inflammation, psoriasis, and/or hypertension comprising administering to a patient in need there of an effective gamma-ketoaldehyde scavenging amount of a gamma-ketoaldehyde scavenging compound.

1 - 3 . (canceled) 
     
     
         4 . A method of treating, preventing, or ameliorating an inflammatory autoimmune response, comprising administering to a patient in need thereof a compound of the following formula: 
       
         
           
           
               
               
           
         
       
       wherein:
 R is C; 
 R 2  is independently H, hydroxy, halogen, nitro, CF 3 , C 1-6  alkyl, C 1-6  alkoxy, C 3-10  cycloalkyl, C 3-8  membered ring containing C, O, S or N, optionally substituted with one or more R 2 , R 3  and R 4 , and may cyclize with to one or more R 2 , R 3 , or R 5  to form an optionally substituted C 3-8  membered ring containing C, O, S or N; 
 R 3  is H, hydroxy, halogen, nitro, CF 3 , C 1-6  alkyl, C 1-6  alkoxy, C 3-10  cycloalkyl, C 3-8  membered ring containing C, O, S or N, optionally substituted with one or more R 4 , R 2  and R 3  may cyclize with to one or more R 2  or R 5  to form an optionally substituted C 3-8  membered ring containing C, O, S or N; 
 R 4  is H, hydroxy, halogen, nitro, CF 3 , C 1-6  alkyl, C 1-6  alkoxy, C 3-10  cycloalkyl, C 3-8  membered ring containing C, O, S or N, optionally substituted with one or more R 4 , R 2  and R 3  may cyclize with to one or more R 2 , R 3 , or R 5  to form an optionally substituted C 3-  membered ring containing C, O, S or N; 
 R 5  is a bond, H, hydroxy, halogen, nitro, CF 3 , C 1-6  alkyl, C 1-6  alkoxy, C 3-10  cycloalkyl, C 3-8  membered ring containing C, O, S or N, optionally substituted with one or more R4, R2 and R 3  may cyclize with to one or more R 2 , R 3 , or R 4  to form an optionally substituted C 3-8  membered ring containing C, O, S or N; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         5 . The method of  claim 4 , 
       wherein:
 R 2  is independently H, substituted or unsubstituted alkyl; 
 R 3  is H, halogen, alkoxy, hydroxyl, nitro; 
 R 4  is H, substituted or unsubstituted alkyl, carboxyl; and stereoisomers and analogs thereof, provided that R 2  is not —CH 2 —OH when R is N, R 4  is H, and R 2  is CH 3 ; and R 5  is a bond; 
 or a pharmaceutically acceptable salt thereof. 
 
     
     
         6 . The method of claim  1 , wherein the compound is of the following formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         7 . (canceled) 
     
     
         8 . The method of claim  1 , wherein the compound is of the following formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         9 . The method of claim  1 , wherein the compound is of the following formula: 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt thereof. 
       
     
     
         10 . The method of  claim 4 , wherein the inflammatory response is in connection with Crohn's disease, inflammatory bowel disease, and ulcerative colitis, asthma, graft versus host disease, chronic obstructive pulmonary disease; autoimmune diseases such as Graves' disease, rheumatoid arthritis, systemic lupus erythematosis, psoriasis. 
     
     
         11 . The method of  claim 4 , wherein the inflammatory response is in connection with Rheumatoid arthritis, osteoarthritis, inflammatory arthropathies (e.g. ankylosing spondylitis, psoriatic arthritis, Reiter's syndrome), acute gout, dysmenorrhoea (menstrual pain), metastatic bone pain, headache and migraine, postoperative pain, mild-to-moderate pain due to inflammation and tissue injury, pyrexia (fever), ileus, and renal colic. 
     
     
         12 . The method of  claim 4 , wherein the patient is in need treatment for (a) reducing inflammation, pain or fever; (b) treating a gastrointestinal disorder; (c) facilitating wound healing; (d) treating or reversing gastrointestinal, renal and/or respiratory toxicity; (e) treating an inflammatory disease, (f) reducing hypertension, and/or (f) treating an ophthalmic disorder in a patient in need thereof. 
     
     
         13 . The method of  claim 12 , wherein the gastrointestinal disorder is an inflammatory bowel disease, Crohn's disease, gastritis, irritable bowel syndrome, constipation, ulcerative colitis, a peptic ulcer, a stress ulcer, a bleeding ulcer, gastric hyperacidity, dyspepsia, gastroparesis, Zollinger-Ellison syndrome, gastroesophageal reflux disease, a bacterial infection, short-bowel (anastomosis) syndrome, or a hypersecretory state associated with systemic mastocytosis or basophilic leukemia and hyperhistaminemia. 
     
     
         14 . The method of  claim 12 , wherein the wound may be an ulcer. 
     
     
         15 . The method of  claim 12 , where the inflammatory disease may be a cardiovascular disorder, reperfusion injury to an ischemic organ, angiogenisis, arthritis, asthma, bronchitis, premature labor, tendinitis, bursitis, an autoimmune disease, an immunological disorder, a skin-related condition, neoplasia, an inflammatory process in a disease, pulmonary inflammation, a central nervous system disorder, allergic rhinitis, respiratory distress syndrome, endotoxin shock syndrome, a microbial infection, a bacterial-induced inflammation, a viral induced inflammation, a urinary disorder, a urological disorder, endothelial dysfunction, organ deterioration, tissue deterioration, a sexual dysfunction or activation, adhesion and infiltration of neutrophils at the site of inflammation. 
     
     
         16 - 25 . (canceled) 
     
     
         17 . The compound of claim  1 , wherein the compound is 2-hydroxybenzylamine, methyl-2-hydroxybenzylamine, or ethyl-2-hydroxybenzylamine.