Aminoalkyloxazole and aminoalkylthiazolecarboxylic acid amides as regeneration-promoting substances for sensory organs and post-mitotic tissue

Abstract

Aminoalkyloxazole and aminoalkylthiazolecarboxylic acid amides of formulae (1) and (2) where X represents O or S, Y represents C or N, where the two atoms must be different from one another, R2 represents hydrogen or acyl and R1 and R3, which may be identical or different, represent a substituent selected from the group consisting of branched or straight-chain, substituted or unsubstituted alkyl groups, alkylcycloalkyl groups, alkylaryl groups, cycloalkyl groups, cycloalkylaryl groups, aryl groups and arylcycloalkyl groups which optionally contain heteroatoms, a pharmaceutically acceptable salt, a stereoisomer, a stereoisomer mixture, a tautomer or a prodrug compound, preferably a prodrug ester and a prodrug peptide, thereof.

1 . Aminoalkyloxazole and aminoalkylthiazolecarboxylic acid amides of formulae (1) and (2) 
       
         
           
           
               
               
           
         
       
       where
 X represents O or S, 
 Y represents C or N, where the two atoms must be different from one another, 
 R2 represents hydrogen or acyl and 
 R1 and R3, which may be identical or different, represent a substituent selected from the group consisting of branched or straight-chain, substituted or unsubstituted alkyl groups, alkylcycloalkyl groups, alkylaryl groups, cycloalkyl groups, cycloalkylaryl groups, aryl groups and arylcycloalkyl groups which optionally contain heteroatoms, 
 a pharmaceutically acceptable salt, a stereoisomer, a stereoisomer mixture, a tautomer or 
 a prodrug compound, preferably a prodrug ester and a prodrug peptide, thereof. 
 
     
     
         2 . The compound as claimed in  claim 1 , which is selected from the group consisting of 
       
         
           
           
               
               
           
         
         a pharmaceutically acceptable salt, a stereoisomer, a stereoisomer mixture, a tautomer or a prodrug compound, preferably a prodrug ester and a prodrug peptide, thereof. 
       
     
     
         3 . A medicament comprising the compound as claimed in  claim 1 . 
     
     
         4 - 5 . (canceled) 
     
     
         6 . A process for preparing the aminoalkyloxazole- and aminoalkylthiazolecarboxylic acid amides as claimed in  claim 1  comprising cyclization to an oxazole or thiazole and subsequent amidation are carried out starting with a natural or unnatural amino acid to be amidated on a solid phase or, using Boc protective group chemistry, in solution. 
     
     
         7 . A pharmaceutical preparation comprising a therapeutically effective amount of at least one aminoalkyloxazole or aminoalkylthiazolecarboxylic acid amide as claimed in  claim 1  alone or in combination and, optionally, further regeneration-promoting active compounds or active compounds, carrier substances, auxiliaries and additives, detergents and adjuvants. 
     
     
         8 . The pharmaceutical preparation as claimed in  claim 7 , formulated for direct (local) or indirect (including systemic) administration to damaged tissue or cochlea of a mammal as a solution, suspension, spray, gel, hydrogel, lotion, emulsion, paste, ointment or creme. 
     
     
         9 . A process for preparing a pharmaceutical preparation as claimed in  claim 7  comprising mixed and/or dissolved components of the preparation with a physical or biological carrier. 
     
     
         10 - 11 . (canceled) 
     
     
         12 . A method for treatment of disorders of humans and animals associated with damaged postmitotic tissues on a basis of regeneration biology comprising administering a therapeutically effective amount of a compound as claimed in  claim 1  directly to damaged tissue structure or systemically. 
     
     
         13 . A method for treatment of inner ear hardness of hearing and restoring hearing of humans and animals after damage and loss of sensory hair cells in an organ of Corti based on regeneration biology, comprising administering a therapeutically effective amount of the compound as claimed in  claim 1  directly or indirectly to damaged tissue structures in a cochlea, optionally by transtympanal injection into a middle ear, by application to a round or oval window of an inner ear or by injection into the inner ear. 
     
     
         14 . A method for treatment of disorders of humans and animals associated with damaged postmitotic tissues on a basis of regeneration biology comprising administering a therapeutically effective amount of the pharmaceutical preparation as claimed in  claim 7  directly to damaged tissue structure or systemically. 
     
     
         15 . A method for treatment of inner ear hardness of hearing and restoring hearing of humans and animals after damage and loss of sensory hair cells in an organ of Corti based on regeneration biology, comprising administering a therapeutically effective amount of the pharmaceutical preparation as claimed in  claim 7  directly or indirectly to damaged tissue structures in a cochlea, optionally by transtympanal injection into a middle ear, by application to a round or oval window of an inner ear or by injection into the inner ear.