Novel compositions for preventing and/or treating degenerative disorders of the central nervous system

Abstract

The present invention provides novel compounds as well as compositions and methods using the same for preventing and/or treating degenerative disorders of the central nervous system. In particular, the present invention provides methods for preventing and/or treating Parkinson's disease.

What is claimed: 
     
         1 . A compound of Formula I: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is C(R 2 )(R 3 )(R 4 ); 
 R 2  is hydrogen, —OH or halogen; 
 R 3  is hydrogen, —OH, halogen or C 1-8  alkyl; 
 R 4  is halogen, C 1-8  alkyl, substituted C 1-8  alkyl, aryl, substituted aryl, alkylcycloalkyl or substituted alkylcycloalkyl; 
 R 3  and R 4  may join with the carbon to which they are attached to form a cycloalkyl ring, which may be optionally substituted, preferably with halogen and more preferably with one or more fluorine atoms; 
 R 6  is hydrogen, C 1-8  alkyl, substituted C 1-8  alkyl, arylalkyl, substituted arylalkyl, alkylaryl, or substituted alkylaryl; 
 Z is optional, when present Z is —(CH 2 ) 1-8 —, —C(═O)—, —S(═O) 2 NH—, —S(═O) 2 —, 
 —C(═S)NH—, —S(═O) 2 —CH 3 , C(═O)—NH—, —S(═O) 2 —NR 9 R 10 , —C(═O)C 1-8  alkyl or 
 —C(═O)CH(NH 2 )CH 3 ; 
 R 9  is hydrogen, C 1-8  alkyl or substituted C 1-8  alkyl; 
 R 10  is hydrogen, C 1-8  alkyl or substituted C 1-8  alkyl; 
 R 5  is hydrogen, C 1-8  alkyl, substituted C 1-8  alkyl, aryl, substituted aryl, C 1-8  alkenyl, substituted C 1-8  alkenyl, arylalkyl, substituted arylalkyl, alkylaryl, substituted alkylaryl, aminoarylalkyl or substituted aminoarylalkyl; 
 R 7  is —OH or halogen; and 
 R 8  is hydrogen, halogen or C 1-8  alkyl, 
 provided that R 2  and R 3  cannot both be hydrogen when R 4  is a halogen, Z is not present, R 7  is —OH, R 5 , R 6  and R 8  are hydrogen. 
 
     
     
         2 . A compound of Formula II: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is C(R 2 )(R 3 )(R 4 ); 
 R 2  is hydrogen, —OH or halogen; 
 R 3  is hydrogen, —OH, halogen or —CH 3 ; 
 R 4  is halogen, —CH 3 , phenyl, fluorophenyl, methylphenyl, cyclohexylmethyl, wherein when R 4  is a halogen, both R 2  and R 3  cannot be hydrogen; 
 R 3  and R 4  may join with the carbon to which they are attached to form a cycloalkyl ring, which may be optionally substituted with one or more halogen atoms; 
 R 6  is hydrogen, phenylalkyl or substituted phenylalkyl; 
 Z is optional, when present Z is —(CH 2 )—, —C(═O)—, —S(═O) 2 NH—, —S(═O) 2 —, 
 —S(═O) 2 —CH 3 , C(═O)—NH—, —S(═O) 2 NR 9 R 10 , —C(═S)—NH— or —C(═O) 2 —CH 3 , 
 R 9  is hydrogen or CH 3 ; 
 R 10  is hydrogen or CH 3 ; 
 R 5  is hydrogen or aminophenylalkyl; 
 R 7  is —OH or halogen; and 
 R 8  is hydrogen, halogen or —CH 3 , 
 provided that R 2  and R 3  cannot both be hydrogen when R 4  is halogen, Z is not present, R 7  is —OH, R 5 , R 6  and R 8  are hydrogen. 
 
     
     
         3 . A compound of Formula III: 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is C(R 2 )(R 3 )(R 4 ); 
 R 2  is hydrogen, —OH or halogen; 
 R 3  is hydrogen, —OH, halogen or —CH 3 ; 
 R 4  is halogen, —CH 3 , phenyl, fluorophenyl, methylphenyl, cyclohexylmethyl, wherein when R 4  is a halogen, both R 2  and R 3  cannot be hydrogen; 
 R 3  and R 4  may join with the carbon to which they are attached to form a cycloalkyl ring, which may be optionally substituted with one or more halogen atoms; 
 R 7  is —OH or halogen; and 
 R 8  is hydrogen, halogen or —CH 3 , 
 provided that R 2  and R 3  cannot both be hydrogen when R 4  is a halogen, R 7  is —OH and R 6  and R 8  are hydrogen. 
 
     
     
         4 . A compound selected from the following: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         5 . The compound of  claim 4  which is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         6 . The compound of  claim 4  which is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         7 . The compound of  claim 4  which is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         8 . The compound of  claim 4  which is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         9 . The compound of  claim 4  which is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         10 . A pharmaceutical composition comprising the compound of  claim 1  and at least one pharmaceutically acceptable carrier. 
     
     
         11 . A method for preventing and/or treating Parkinson's disease in a patient at risk for developing or diagnosed with the same, which comprises administering to the patient in need thereof an effective amount of a compound of  claim 1 . 
     
     
         12 . A method for preventing and/or treating Parkinson's disease in a patient at risk for developing or diagnosed with the same, which comprises administering to the patient in need thereof an effective amount of a compound of  claim 2 . 
     
     
         13 . A method for preventing and/or treating Parkinson's disease in a patient at risk for developing or diagnosed with the same, which comprises administering to the patient in need thereof an effective amount of a compound of  claim 3 . 
     
     
         14 . A method for preventing and/or treating Parkinson's disease in a patient at risk for developing or diagnosed with the same, which comprises administering to the patient in need thereof an effective amount of a compound of  claim 4 . 
     
     
         15 . The method of  claim 14 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         16 . The method of  claim 14 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         17 . The method of  claim 14 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         18 . The method of  claim 14 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         19 . The method of  claim 14 , wherein the compound is: 
       
         
           
           
               
               
           
         
       
       or a pharmaceutically acceptable salt, solvate, or prodrug thereof. 
     
     
         20 . The method of  claim 11 , further comprising administering an effective amount of at least one other therapeutic agent. 
     
     
         21 . The method of  claim 11 , wherein at least one other therapeutic agent is levodopa, an anticholinergic, a catechol-O-methyl transferase inhibitor, a dopamine receptor agonist, a monoamine oxidase inhibitor, a peripheral decarboxylase inhibitor, or an anti-inflammatory agent. 
     
     
         22 . A kit comprising:
 a container having an effective amount of a compound of  claim 1 , or a pharmaceutically acceptable salt, solvate, or prodrug thereof, or any combination of two or more thereof; and   instructions for using the same to prevent and/or treat Parkinson's disease.