Use of benzylideneaminoguanidines and hydroxyguanidines as melanocortin receptor ligands

Abstract

The present invention relates to the use of compounds of general formula (I) as ligands to the melanocortin receptors and/or for treatment of disorders in the melanocortin system: wherein X is H or OH; R1, R2, R3, R4 and R5 are the same or different and are selected from hydrogen, halogen, alkyl having 1 to 5 carbon atoms, electron donor groups such as alkoxy having 1-5 carbon atoms or hydroxy, electron acceptor groups selected from cyano, nitro, trifluoroalkyl or amide; alkylamino, benzoyloxy, nitroxy, phenyl or sulpho; and the pharmacologically active salts thereof.

1 . A method of treating allergic disorder comprising administering to a patient in need thereof an effective amount of a compound of formula (I)  
       
         
           
           
               
               
           
         
       
       wherein R1, R2, R3, R4 and R5 are the same or different and are selected from hydrogen, halogen, and methyl; from electron donor groups such as methoxy or hydroxy; and from electron acceptor groups selected from nitro or sulpho; or a pharmacologically active salt thereof; and 
 wherein the allergic disorder is a fast allergic disorder (type I allergy).  
 
     
     
         2 . The method according to  claim 1 , wherein one or more of R1, R2, R3, R4 and R5 are methyl.  
     
     
         3 . The method according to  claim 1 , wherein one or more of R1, R2, R3, R4 and R5 are methoxy.  
     
     
         4 . The method according to  claim 1 , wherein one or more of R1, R2, R3, R4 and R5 are halogen atoms.  
     
     
         5 . The method according to  claim 4  wherein the halogen is fluoro or chloro.  
     
     
         6 . The method of  claim 1 , wherein the compound of formula (I) is: 
 N-(2-Hydroxy-4,6-dimethoxybenzylideneamino)guanidine acetate;    N-(3-Bromo-4-fluorobenzylideneamino)guanidine acetate;    N-(2,3-Difluorobenzylideneamino)guanidine acetate;    N-(4-Chloro-3-fluorobenzylideneamino)guanidine acetate;    N-(3-Methoxy-2,6-dinitrobenzylideneamino)guanidine hydrochloride;    N-(3-Bromo-2,6-dinitrobenzylideneamino)guanidine hydrochloride;    N-(2,3-Dimethoxy-5,6-dinitrobenzylideneamino)guanidine acetate;    N-(5-Bromo-2,4-dimethoxybenzylideneamino)guanidine acetate 0.5 hydrate;    N-(2,3-Dimethoxy-5-nitrobenzylideneamino)guanidine acetate;    N-(3,4-Difluorobenzylideneamino)guanidine acetate;    N-(2-Fluoro-5-nitrobenzylideneamino)guanidine acetate;    N-(4-Bromo-2-fluorobenzylideneamino)guanidine acetate;    N-(3,5-Dinitrobenzylideneamino)guanidine acetate dihydrate;    N-(3-Chloro-4-fluorobenzylideneamino)guanidine acetate;    N-(2-Bromo-4-nitroobnzylideneamino)guanidine acetate;    N-(2-Bromo-5-nitroobenzylideneamino)guanidine acetate;    N-(2-Iodobenzylideneamino)guanidine acetate;    N-(2,3-Dimethoxy-5-nitrobenzylideneamino)guanidine hydrochloride;    N-(2-Hydroxy-4-methoxybenzylideneamino)guanidine acetate;    N-(4-Bromo-3-nitrobenzylideneamino)guanidine acetate;    N-(6-Chloro-2,3-dinitrobenzylideneamino)guanidine hydrochloride;    N-(3-Iodobenzylideneamino)guanidine hydrochloride;    N-(2-Sulphobenzylideneamino)guanidine hydrochloride;    N-(4-Fluoro-3-nitrobenzylideneamino)guanidine acetate;    N-(4-Methoxy-3-nitrobenzylideneamino)guanidine acetate;    N-(3,5-Dichloro-2-nitrobenzylideneamino)guanidine acetate;    N-(2-Hydroxy-3-methoxy-5-nitrobenzylideneamino)guanidine hydrochloride;    N-(2-Hydroxy-4-methoxy-5-nitrobenzylideneamino)guanidine hemiacetate;    N-(-3-Chloro-4-methoxy-5-nitrobenzylideneamino)guanidine;    N-(3,5-Dichloro-4-methoxybenzylideneamino)guanidine acetate;    N-(3-Bromo-4-methoxy-5-methylbenzylideneamino)guanidine acetate;    N-(2,3,4-Trimethoxybenzylideneamino)guanidine hydrochloride;    N-(4-Chloro-2-methoxy-5-nitrobenzylideneamino)guanidine acetate;    N-(3,6-Dichloro-2-nitrobenzylideneamino)guanidine acetate;    N-(2-Hydroxy-4-methyl-5-nitrobenzylideneamino)guanidine hydrochloride;    N-(3-Hydroxy-4-methyl-2-nitrobenzylideneamino)guanidine acetate;    N-(5-Bromo-2-hydroxy-3-nitrobenzylideneamino)guanidine hydrochloride;    N-(5-Bromo-2-mehoxy-3-nitrobenzylideneamino)guanidine hydrochloride;    N-(2,4-Dimethoxy-5-nitrobenzylideneamino)guanidine acetate;    N-(4-Bromo-2-fluoro-5-nitrobenzylideneamino)guanidine acetate;    or a pharmacologically acceptable salt thereof.    
     
     
         7 . The method as claimed in  claim 1  where additionally is present a label, preferably a radioactive label, or a toxic agent.  
     
     
         8 . The method as claimed in  claim 1 , wherein a prodrug from which a compound as defined in  claim 1  is formed in vivo for treatment of fast allergic disorders (type I allergy).  
     
     
         9 . The method as claimed in  claim 1 , wherein a compound as claimed in  claim 1 , together with one or more adjuvants, carriers or excipients, is present in a pharmaceutical composition.  
     
     
         10 - 28 . (canceled)  
     
     
         29 . The method of  claim 1 , wherein the fast allergic disorder (type I allergy) is selected from the group consisting of anaphylactic reactions, anaphylactoid reactions, asthma, asthma of allergic type, asthma of unknown origin, rhinitis, hay fever and pollen allergy.