Compounds with a sulphonamide group and pharmaceutical compositions containing these compounds

Abstract

This invention relates to compounds that as prodrugs and/or vehicles make it possible for an active ingredient to be taken up into erythrocytes and/or an active ingredient to bind to erythrocytes, whereby the uptake of the compounds into erythrocytes and/or the binding of the compounds to erythrocytes is made possible by a group —SO 2 NR 1 R 2 , whereby R 1 and R 2 , independently of one another, mean a hydrogen atom, an acyl group, an alkyl group, a cycloalkyl group, an aryl group, a cyano group or a hydroxy group. By the prodrugs according to the invention, active ingredients, such as endogenous substances, natural substances and synthetic substances with therapeutically valuable properties with a high “first pass” effect are made available orally to a reasonable extent or are decisively improved relative to oral activity.

1 - 26 . (canceled) 
   
   
       27 . Compound that as a prodrug and/or vehicle makes it possible to take up an active ingredient into erythrocytes and/or to bind an active ingredient to erythrocytes, characterized in that the uptake of the compound into erythrocytes and/or the binding of the compound to erythrocytes is made possible by a group
   —SO 2 NR 1 R 2      
     whereby R 1  and R 2 , independently of one another, is a hydrogen atom, an acyl radical, an alkyl radical, a cycloalkyl radical, an aryl radical, a cyano group or a hydroxy group. 
   
   
       28 . Compound according to  claim 27 , whereby the uptake of the compound into erythrocytes and/or the binding of the compound to erythrocytes is carried out via hemoglobin, membrane proteins and/or carboanhydrase. 
   
   
       29 . Compound according to  claim 27 , whereby a depot of the active ingredient in the erythrocytes is formed by the uptake of the compound into erythrocytes and/or by the binding of the compound to erythrocytes, whereby an essential part of the active ingredient is present in the body in erythrocytes. 
   
   
       30 . Compound according to  claim 29 , whereby the compound is enriched in the erythrocytes by a factor 10 to 1000 above the plasma level. 
   
   
       31 . Compound according to  claim 27 , whereby the compound is a compound that exerts its action in the erythrocytes. 
   
   
       32 . Compound according to  claim 28 , wherein the compound is a prodrug that has the following structure:
 Active ingredient—[Spacer]n-SO 2 NR 1 R2   
     whereby n means a number 0 or 1, R 1  and R2 have the meaning that is given in claim  1 , and the active ingredient in its free form has a functional group. 
   
   
       33 . Compound according to  claim 32 , whereby one of radicals R 1  and R 2  means a hydrogen atom. 
   
   
       34 . Compound according to  claim 33 , whereby R 1  and R 2  mean a hydrogen atom. 
   
   
       35 . Compound according to  claim 32 , whereby the compound and/or the active ingredient that is contained in the compound prevents the parasitic attack of the erythrocytes. 
   
   
       36 . Compound according to  claim 35 , whereby the active ingredient is an anti-malaria agent, such as arteether, artemether, artesunate, chloroquine, pamaquine, primaquine, pyrethamine, mefloquine, proguanil, cinchonidine, cinchonine, hydroxychloroquine, pamaquine, primaquine, pyrimethamine, quinine or a quinine derivative, such as quinine-bisulfate, quinine-carbonate, quinine-dihydrobromide, quinine-dihydrochloride, quinine-ethylcarbonate, quinine-formate, quinine-gluconate, quinine-hydroiodide, quinine-hydrochloride, quinine-salicylate or quinine-sulfate. 
   
   
       37 . Compound according to  claim 27 , whereby the therapeutically desired action is carried out by release, especially hydrolytic cleavage, of the active ingredient that is contained in the prodrug and/or its metabolites. 
   
   
       38 . Compound according to  claim 32 , whereby n is 0, and the functional group is a group —OH, which forms a group —O—SO 2 NH 2  with the group —SO 2 NH 2 ;
 a group=O, which is converted into a group=N—OH or =N—NH 2  and forms a group=N—O—SO 2 NH 2  or =N—NH—SO 2 NH 2  with the group —SO 2 NH 2 ;   a group —NHR, which forms a group —NR—SO 2 NH 2  with the group —SO 2 NH 2 , whereby R is a hydrogen atom or an alkyl radical or NR is part of a heterocyclic ring system, or   a group —SH, which forms a group —S—SO 2 NH 2  with the group —SO 2 NH 2 .   
   
   
       39 . Compound according to  claim 32 , whereby n is 1, and the functional group is a group
 —COOH, which together with the spacer and with the group —SO 2 NH 2  forms a group —C(O)-spacer-SO 2 NH 2 .   
   
   
       40 . Compound according to  claim 37 , whereby the spacer is a group -A-B-(O) s , whereby s is a number 0 or 1, A stands for S, O or NR 3 , whereby R 3  is a hydrogen atom, an alkyl radical or an acyl radical, and B is selected from an alkylene group, an arylene group, an alkylene arylene group or an alkylene arylenealkylene group, which optionally are substituted. 
   
   
       41 . Compound according to  claim 34 , whereby n is 1, and the functional group is a group
 —YH, which together with the spacer and with the group —SO 2 NH 2  forms a group -Y-spacer-SO 2 NH 2 , whereby Y stands for S, O or NR 4 , whereby R 4  is a hydrogen atom, an alkyl radical or an acyl radical, or NR 4  is part of a heterocyclic ring system.   
   
   
       42 . Compound according to  claim 41 , whereby the spacer is a group 
     
       
         
         
             
             
         
       
     
     whereby t and p are a number 0 or 1, and E is selected from an alkylene group, an arylene group, an alkylene arylene group or an alkylene arylenealkylene group, which optionally are substituted; or 
     
       
         
         
             
             
         
       
     
     whereby q and n are a number 0 or 1, R 5  and R 6 , independently of one another, mean a hydrogen atom or an alkyl radical, and D means an arylene group, especially a phenylene group, which optionally can be substituted; or 
     
       
         
         
             
             
         
       
     
     whereby r and v are a number 0 or 1, and m means a number from 1 to 15. 
   
   
       43 . Compound according to  claim 42 , whereby the functional group is a group —OH. 
   
   
       44 . Compound according to  claim 32 , whereby the active ingredient is selected from androgens, anabolic agents, antiandrogens, estrogens, gestagens, glucocorticoids, amoebicides, anti-diuretic agents, antigonatropines, ulcer therapeutic agents, neuropharmaceutical agents, dopamine receptor antagonists, dopamine, apomorphine, melatonin and peptides, such as GnRH, and other hypothalamic, regulatory active peptides. 
   
   
       45 . Compound according to  claim 44 , whereby the active ingredient is an androgen, and the functional group is the 17-hydroxy group or the 3-carbonyl group of the androgen; or
 an estrogen, and the functional group is a 3-, 16- or 17-hydroxy group or 17-carbonyl group; or   a gestagen, and the functional group is a 17-hydroxy group or a 3-carbonyl group.   
   
   
       46 . Compound according to  claim 45 , whereby the active ingredient is testosterone;
 estradiol, estriol or estrone; or   norethisterone, dienogest, drospirenone or levonorgestrel.