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 . The use of a compound of general 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; as a melanocortin receptor ligand and/or in the preparation of a medicament for treatment of disorders related to the melanocortin system.  
     
     
         2 . Use according to  claim 1 , wherein one or more of R1, R2, R3, R4 and R5 are methyl.  
     
     
         3 . Use according to  claim 1  or  claim 2 , wherein one or more of R1, R2, R3, R4 and R5 are methoxy.  
     
     
         4 . Use according to any one of the previous claims wherein one or more of R1, R2, R3, R4 and R5 are halogen atoms.  
     
     
         5 . Use according to  claim 4  wherein the halogen is fluoro or chloro.  
     
     
         6 . Use of a compound selected from: 
 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-nitroobenzylideneamino)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-(3,6Dichloro-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-methoxy-3-nitrobenzylideneamino)guanide hydrochloride    N-(2,4-Dimethoxy-5-nitrobenzylideneamino)guanidine acetate    N-(4-Bromo-2-fluoro-5-nitrobenzylideneamino)guanidine acetate    or a pharmacologically acceptable salt thereof, as a melanocortin receptor ligand and/or in the preparation of a medicament for treatment of disorders related to the melanocortin system.    
     
     
         7 . Use as claimed in any one of the previous claims where additionally is present a label, preferably a radioactive label, or a toxic agent.  
     
     
         8 . Use of a prodrug from which a compound as defined in any one of  claims 1  to  7  is formed in vivo, wherein the compound is used as a melanocortin receptor ligand and/or for treatment of disorders related to the melanocortin system.  
     
     
         9 . Use of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8 , together with one or more adjuvants, carriers or excipients, in a pharmaceutical composition.  
     
     
         10 . Use of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8  in the production of a medicament for the treatment of dysfunctions of the endocrine system or an hormonal system.  
     
     
         11 . Use of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8  in the production of a medicament for the treatment of sexual functions and/or sexual dysfunctions.  
     
     
         12 . Use of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8  in the production of a medicament for the treatment of allergic disorders.  
     
     
         13 . Use of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8  in the production of a medicament for the treatment of pain.  
     
     
         14 . Use of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8  in the production of a medicament for inducing skin tanning or for inducing lighter skin colour.  
     
     
         15 . Use of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8  in the production of a medicament for the treatment of anorexic conditions such as those caused by cancer, cachexia, geriatric conditions, HIV, trauma and psychological conditions.  
     
     
         16 . Use of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8  in the production of a medicament for inducing peripheral nerve regeneration.  
     
     
         17 . Use of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8  in the production of a medicament for inducing central nerve regeneration.  
     
     
         18 . A method of treating dysfunctions of the endocrine system or an hormonal system comprising the use or administration of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8 .  
     
     
         19 . A method of treating sexual functions and/or sexual dysfunctions comprising the use or administration of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8 .  
     
     
         20 . A method of treating pain comprising the use or administration of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8 .  
     
     
         21 . A method of inducing skin tanning or for inducing lighter skin colour comprising the use or administration of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8 .  
     
     
         22 . A method of treating anorexic conditions such as those caused by cancer, cachexia, geriatric conditions, HIV, trauma and psychological conditions comprising the use or administration of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8 .  
     
     
         23 . A method of inducing peripheral nerve regeneration comprising the use or administration of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8 .  
     
     
         24 . A method of inducing central nerve regeneration comprising the use or administration of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8 .  
     
     
         25 . Use of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8  in the production of a medicament for the treatment of skin disorders, including for the treatment of melanoma.  
     
     
         26 . Use of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8  in the production of a medicament for the treatment and/or diagnosis of malignancies, such as melanoma and metastases.  
     
     
         27 . A method of treating a skin disorder, including the treatment of melanoma, comprising the use or administration of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8 .  
     
     
         28 . A method of treating and/or diagnosing malignancies, such as melanoma and metastases, comprising the use or administration of a compound as claimed in any one of  claims 1  to  7  or a prodrug as claimed in  claim 8.