Cannabinoids

Abstract

Compounds of the formula: wherein R, R1 and R4 are defined in the specification, and pharmaceutically acceptable salts, esters and tautomers thereof, having activity at peripheral cannabinoid receptors, commonly designated the CB2 receptor class. The compounds are useful for therapy, especially in the treatment of pain, inflammation and autoimmune disease.

1 . A compound of general formula I  
       
         
           
           
               
               
           
         
         wherein:  
         R is selected from the group consisting of optionally substituted carbocyclic and heterocyclic rings;  
         R1 is independently selected at each occurrence from the group consisting of hydrogen and C 1-6  alkyl;  
         R4 is selected from the group consisting of optionally substituted C 1-10  alkyl and alkenyl;  
         and pharmaceutically acceptable salts, esters or tautomers of such cpmpound.  
       
     
     
         2 . A compound as claimed in  claim 1  wherein R is optionally substituted aryl, cycloalkyl or cyclothioalkyl.  
     
     
         3 . A compound as claimed in  claim 2  wherein R is selected from the group consisting of phenyl, cyclohexyl, cycloheptyl, cyclohexenyl, cyclopentyl, tetrahydrothiopyranyl, methandienyl, cycloheptyl, adamantanyl, tetrahydrothiophen-3-yl, 1-alkyl-pipendinyl, 4-aryl-cyclohexyl, 3,3-dialkylcyclohexyl, tetrahydropyranyl, 1-cyclohexanolyl, 14dioxospirocycloalkyl and cyclohex-3-enonyl.  
     
     
         4 . A compound as claimed in  claim 1  wherein R1 is hydrogen or methyl.  
     
     
         5 . A compound as claimed in  claim 1  wherein R4 is linear C 5-7  alkyl.  
     
     
         6 . A compound as claimed in  claim 5 , wherein R4 is hexyl.  
     
     
         7 . A compound of general formula II:  
       
         
           
           
               
               
           
         
         wherein R1 is independently selected at each occurrence from the group consisting of hydrogen and C 1-6  alkyl;  
         R4 is selected from the group consisting of C 1-10  alkyl and alkenyl; and  
         R5 is C 1-6  alkyl  
         and analogues thereof which have a 1-position hydroxyl group on the cyclohexane ring.  
       
     
     
         8 . A compound as claimed in  claim 7 , wherein R5 is methyl or ethyl.  
     
     
         9 . A compound as claimed in  claim 7  wherein R1 is hydrogen or methyl.  
     
     
         10 . A compound as claimed in  claim 7 , wherein R1 is hydrogen.  
     
     
         11 . A compound of the formula  
       
         
           
           
               
               
           
         
         and the 2,6-dimethoxyphenyl analogues thereof.  
       
     
     
         12 . A compound selected from the group consisting of: 
 2-(3-methylcyclohexyl)-5-(1,1′-dimethylheptyl)-resorcinol;    2-(3-methylcyclohexyl)-5-(1,1′-dimethylheptyl)-resorcinol;    2-(3R-methylcyclohexyl)-5-(1,1′-dimethylheptyl)-resorcinol; and    1-{4-(1,1-Dimethyl-heptyl)-2,6-dimethoxy-phenyl}-3-methyl-cyclohexanol.    
     
     
         13 . A composition comprising a compound of formula I, together with a pharmaceutically acceptable carder and/or excipient.  
     
     
         14 . A composition comprising a compound of formula II together with a pharmaceutically acceptable carrier and/or excipient.  
     
     
         15 . A method of treating pain comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I.  
     
     
         16 . A method of treating pain comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula II.  
     
     
         17 . A method as claimed in  claim 13 , wherein said pain is peripheral pain.  
     
     
         18 . A composition comprising a compound of formula I or II together with a pharmaceutically acceptable carrier and/or excipient. The composition should be sterile and, if intended for injection, non-pyrogenic  
     
     
         19 . A method of treating inflammation comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I.  
     
     
         20 . A method of treating inflammation comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula II.  
     
     
         21 . A method of treating autoimmune disease comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula I.  
     
     
         22 . A method of treating autoimmune disease comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula II.  
     
     
         23 . A compound of formula I for use in therapy.  
     
     
         24 . Use of a compound of formula I for the manufacture of a medicament for the treatment of a pain, inflammation and autoimmune disease.