Amino acid derivatives used as pharmaceutical substances

Abstract

The invention relates to a method for improving bioavailability of pharmaceutical substances and for allowing the pharmaceutical substances to permeate the blood-brain barrier, the pharmaceutical substances having at least one or more amidine, guanidine, N-hydroxyamidine (amidoxime) or N-hydroxyguanidine functions. The invention also relates to medicaments containing the correspondingly modified pharmaceutical substances.

1 .- 16 . (canceled) 
     
     
         17 . A method of producing a prodrug for a medicinal substance having at least one function selected from the group consisting of amidine functions, N-hydroxyamidine (amidoxime) functions, guanidine functions and N-hydroxyguanidine functions, the method comprising substituting the at least one function of the medicinal substance with a partial structure of formula (I), formula (II) or formula (III), 
       
         
           
           
               
               
           
         
       
       thereby producing the prodrug, wherein R1 is selected from the group consisting of hydrogen, an alkyl radical, an aryl radical, and one selected from the group consisting of the following: 
       
         
           
           
               
               
           
         
       
       and the salts thereof. 
     
     
         18 . The method according to  claim 17 , wherein the prodrug has at least one of improved solubility, bioavailability, and capacity to pass the blood-brain barrier compared to the medicinal substance. 
     
     
         19 . The method according to  claim 17 , wherein the medicinal substance is selected from the group consisting of protease inhibitors, DNA-intercalating compounds, RNA-intercalating compounds, inhibitors of viral enzymes and N-methyl-D-aspartate receptor antagonists. 
     
     
         20 . The method according to  claim 19 , wherein the protease inhibitor is a thrombin inhibitor, an inhibitor of factor Xa, Factor VII or all of the proteases of the coagulation cascade, or a matriptase inhibitor. 
     
     
         21 . The method according to  claim 19 , wherein the DNA-intercalating compound or RNA-intercalating compound is pentamidine, diminazene or isometamidium. 
     
     
         22 . The method according to  claim 19 , wherein the inhibitor of viral enzymes is a neuraminidase inhibitor. 
     
     
         23 . The method according to  claim 17 , wherein the prodrug comprises a plurality of at least one of the partial structures of formulas (I), (II) and (III). 
     
     
         24 . The method according to  claim 17 , wherein the medicinal substance is configured for the prophylaxis and therapy of visceral and/or cutaneous leishmaniasis, trypanosomiasis, the 2 nd  phase of trypanosomiasis, or pneumonia caused by pneumocystis carinii, for inhibiting the growth of malign tumors, for inhibiting blood coagulation, for blood pressure reduction, for neuroprotection, or for combating viral infections. 
     
     
         25 . A prodrug for a medicinal substance having at least one function selected from the group consisting of amidine functions, N-hydroxyamidine (amidoxime) functions, guanidine functions and N-hydroxyguanidine functions, the prodrug comprising a partial structure having the formula (I), (II) or (III), 
       
         
           
           
               
               
           
         
       
       wherein R1 is selected from the group consisting of hydrogen, an alkyl radical, an aryl radical, and one selected from the group consisting of the following: 
       
         
           
           
               
               
           
         
       
       and the salts thereof, 
       wherein the partial structure replaces the at least one function in the medicinal substance. 
     
     
         26 . The prodrug according to  claim 25 , wherein the medicinal substance is selected from the group consisting of protease inhibitors, DNA-intercalating compounds, RNA-intercalating compounds, inhibitors of viral enzymes and N-methyl-D-aspartate receptor antagonists 
     
     
         27 . The prodrug according to  claim 26 , wherein the protease inhibitor is a thrombin inhibitor, an inhibitor of factor Xa, Factor VII or all of the proteases of the coagulation cascade, or a matriptase inhibitor. 
     
     
         28 . The prodrug according to  claim 26 , wherein the DNA-intercalating compound or RNA-intercalating compound is pentamidine, diminazene or isometamidium. 
     
     
         29 . The prodrug according to  claim 26 , wherein the inhibitor of viral enzymes is a neuraminidase inhibitor. 
     
     
         30 . The prodrug according to  claim 25 , wherein the medicinal substance is configured for the prophylaxis and therapy of visceral and/or cutaneous leishmaniasis, trypanosomiasis, the 2 nd  phase of trypanosomiasis, or pneumonia caused by pneumocystis carinii, for inhibiting the growth of malign tumors, for inhibiting blood coagulation, for blood pressure reduction, for neuroprotection, or for combating viral infections. 
     
     
         31 . The prodrug according to  claim 25 , wherein the prodrug comprises a plurality of at least one of the partial structures of formulas (I), (II) and (III). 
     
     
         32 . A pharmaceutical composition comprising the prodrug of  claim 25 .