Cyclohexenyl compounds, compositions comprising them and methods

Abstract

The present invention is directed to phenyl substituted cyclohexenyl compounds, compositions comprising them and uses thereof for the preparation of medicaments for the treatment of obesity and any disease or disorder associated therewith, for reduction in food consumption, and for the treatment of inflammation and disorders associated therewith.

1 . A compound of general formula (I): 
       
         
           
           
               
               
           
         
       
       wherein
 R 1 , R 2  and R 3  are each independently a straight or branched C 1 -C 10  alkyl, C 2 -C 10  alkenyl or C 2 -C 10  alkynyl; each independently optionally substituted by at least one substituent selected from hydroxy, halogen. 
 R 4  is a straight or branched C 1 -C 10  alkyl, C 2 -C 10  alkenyl or C 2 -C 10  alkynyl which is substituted by at least one substituent of general formula (II): 
 
       
         
           
           
               
               
           
         
       
       wherein
 X is selected from N, N + H, N + (C 1 -C 10  alkyl), O + , S + , P, P + H; 
 R 5  and R 6  are each independently selected from H, C 1 -C 10  alkyl, C 2 -C 10  alkenyl or C 2 -C 10  alkynyl; or both R 5  and R 6  together with X may form a C 3 -C 8  heterocyclic ring; 
 wherein R 5  and R 6  may each independently be optionally interrupted by at least one heteroatom selected from —O—, —NH—, N + (C 1 -C 10  alkyl), —S—; 
 including any salt, enantiomer, diastereomer or mixtures thereof. 
 
     
     
         2 . A compound according to  claim 1 , wherein X is selected from N and N + H. 
     
     
         3 . A compound according to  claim 1 , wherein X is N + H. 
     
     
         4 . A compound according to  claim 1 , wherein R 5  and R 6  form together with X a C 3 -C 8  heterocyclic ring. 
     
     
         5 . A compound according to  claim 4 , wherein said heterocyclic ring is further interrupted by at least one heteroatom selected from —O—, —NH—, —S—. 
     
     
         6 . A compound according to  claim 1 , wherein R 4  is a straight or branched C 1 -C 5  alkyl substituted by a substituent of the general formula (III): 
       
         
           
           
               
               
           
         
       
       wherein
 m and n are each independently an integer selected from 0-5; wherein at least one of m or n is different than 0; 
 X is selected from N, N + H, N + (C 1 -C 10  alkyl), O + , S + , P or P + H; 
 Y is selected from —O—, —NH—, —S—, straight or branched C 1 -C 6  alkylene, straight or branched C 2 -C 6  alkenylene; straight or branched C 2 -C 6  alkynylene. 
 
     
     
         7 . A compound of  claim 6 , wherein X is selected from N and N + H. 
     
     
         8 . A compound according to  claim 6 , wherein Y is —O—. 
     
     
         9 . A compound according to  claim 1 , wherein R 1  and R 2  are each independently a slight or branched C 1 -C 5  alkyl. 
     
     
         10 . A compound according to  claim 1 , wherein R 3  is a slight or branched C 4 -C 10  alkyl. 
     
     
         11 . A compound according to  claim 1 , wherein substituents on positions 3 and 4 of compound of general formula (I) have a cis configuration. 
     
     
         12 . A compound according to  claim 11 , wherein conformation of substituents on positions 3 and 4 of compound of general formula (I) are equatorial:axial or axial:equatorial. 
     
     
         13 . A compound according to  claim 1 , wherein substituents on positions 3 and 4 of compound of general formula (I) have a trans configuration. 
     
     
         14 . A compound according to  claim 13 , wherein conformation of substituents on positions 3 and 4 of compound of general formula (I) are equatorial:equatorial or axial:axial. 
     
     
         15 . A compound according to  claim 1 , being substantially devoid of affinity to a CB receptor. 
     
     
         16 - 21 . (canceled) 
     
     
         22 . A pharmaceutical composition comprising at least one compound according to  claim 1 , and a pharmaceutically acceptable carrier. 
     
     
         23 . An anti-obesity pharmaceutical composition according to  claim 22 , in an amount therapeutically effective to treat obesity or any disease or disorder associated therewith. 
     
     
         24 . A method of treating obesity or any disease or disorder associated therewith in a subject in need thereof, said method comprising administering to the subject in need thereof a therapeutically effective amount of at least one compound according to  claim 1 . 
     
     
         25 . An anti-abnormal food consumption and anti-abnormal body weight compositions according to  claim 22  in an amount therapeutically effective to treat abnormal food consumption or abnormal body weight and any disease, disorder, condition or symptoms associated therewith. 
     
     
         26 . A method of treating abnormal food consumption or anti-abnormal body weight, or a disease or disorder related thereto, in a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of at least one compound according to  claim 1 . 
     
     
         27 . An analgesic compound according to  claim 1 , for use in the treatment of pain including any condition or symptom associated therewith. 
     
     
         28 . A compound according to  claim 27 , wherein said pain is chronic pain. 
     
     
         29 . A method of treating pain in a subject in need thereof, comprising administering to a subject in need thereof a therapeutically effective amount of at least one compound according to  claim 1  to treat the pain, or any disease, disorder, condition or symptom associated therewith. 
     
     
         30 . An analgesic pharmaceutical composition according to  claim 22  in an amount therapeutically effective to treat pain, or any condition or symptom associated therewith. 
     
     
         31 . An anti-inflammatory pharmaceutical composition according to  claim 22  in an amount therapeutically effective to treat inflammation, or any condition or symptom associated therewith. 
     
     
         32 . A method of treating inflammation, or any condition or symptom associated therewith, in a subject in need thereof, the method comprising administering to the subject in need thereof a therapeutically effective amount of at least one compound according to  claim 1  to treat the inflammation, or any disease, disorder, condition or symptom associated therewith. 
     
     
         33 . The method of  claim 26 , wherein the method comprises reducing food consumption or body weight in a subject in need thereof by administering a therapeutically effective amount of the compound.