Azaindoles having serotonin receptor affinity

Abstract

Described herein are compounds with affinity for the 5-HT 6 receptor, which have the general formula I: wherein A, B, D, E, R 1 to R 3 and n are described herein. Also described is the use of these compounds as pharmaceuticals to treat indications where inhibition of the 5-HT 6 receptor is implicated, such as schizophrenia.

1 - 7 . (canceled) 
     
     
         8 . A compound according to the following formula: 
       
         
           
           
               
               
           
         
         wherein: 
         one of A, B, D, or E is N, and the remainder are CH groups; 
         R1 is selected from the group consisting of SO 2 Ar, C(O)Ar, CH 2 Ar and Ar; 
         R2 and R3 are independently selected from the group consisting of H and alkyl; 
         — represents a single or double bond, wherein there is only one double bond in the ring at a time; 
         n is an integer of from 1-3; and 
         Ar is an optionally substituted aryl group; 
         or salts, solvates, or hydrates thereof. 
       
     
     
         9 . A compound according to claim  1  wherein R1 is selected from the group consisting of SO 2 Ar and C(O)Ar. 
     
     
         10 . A compound according to claim  1  wherein R1 is SO 2 Ar. 
     
     
         11 . A compound according to claim  3  wherein Ar is selected from the group consisting of substituted phenyl and naphthyl. 
     
     
         12 . A compound according to claim  4  wherein Ar is naphthyl. 
     
     
         13 . A pharmaceutical composition comprising a compound according to the following formula: 
       
         
           
           
               
               
           
         
         wherein: 
         one of A, B, D, or E is N, and the remainder are CH groups; 
         R1 is selected from the group consisting of SO 2 Ar, C(O)Ar, CH 2 Ar and Ar; 
         R2 and R3 are independently selected from the group consisting of H and alkyl; 
         — represents a single or double bond, wherein there is only one double bond in the ring at a time; 
         n is an integer of from 1-3; and 
         Ar is an optionally substituted aryl group; 
         or salts, solvates, or hydrates thereof, in an amount effective to antagonize the 5-HT 6  receptor; and 
         a pharmaceutically acceptable carrier. 
       
     
     
         14 . A pharmaceutical composition suitable for treating one or more conditions selected from the group consisting of schizophrenia, psychosis, depression, Parkinsonism, amyotrophic lateral sclerosis, Alzheimer's disease, and Huntington's disease, the composition comprising a pharmaceutically acceptable carrier and a compound of  claim 13 , or a salt, solvate, or hydrate thereof, in an amount effective to antagonize a 5-HT 6  receptor. 
     
     
         15 . A method of treating a patient having a medical condition for which a 5-HT 6  antagonist is indicated comprising the step of administering to the patient a pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of  claim 13 , or a salt, solvate, or hydrate thereof, in an amount effective to antagonize a 5-HT 6  receptor. 
     
     
         16 . A method of treatment of one or more conditions selected from the group consisting of schizophrenia, psychosis, depression, Parkinsonism, amyotrophic lateral sclerosis, for treating a patient having Alzheimer's disease, and Huntington's disease the method comprising the step of administering to a patient having such condition an effective amount of a pharmaceutical composition comprising a compound of  claim 13 , or a salt, solvate, or hydrate thereof, and a pharmaceutically acceptable carrier in an amount effective to antagonize a 5-HT 6  receptor. 
     
     
         17 . A pharmaceutical composition comprising a compound according to the following formula: 
       
         
           
           
               
               
           
         
         wherein: 
         one of A, B, D, or E is N, and the remainder are CH groups; 
         R1 is selected from the group consisting of SO 2 Ar, C(O)Ar, CH 2 Ar and Ar; 
         R2 and R3 are independently selected from the group consisting of H and alkyl; 
         — represents a single or double bond, with the proviso that there is only one double bond in the ring at a time; 
         n is an integer of from 1-3; and 
         Ar is an optionally substituted aryl group; or 
         salts, solvates, or hydrates thereof, in an amount effective to antagonize the 5-HT 7  receptor; and 
         a pharmaceutically acceptable carrier. 
       
     
     
         18 . A pharmaceutical composition suitable for treating one or more conditions selected from the group consisting of schizophrenia, psychosis, depression, Parkinsonism, amyotrophic lateral sclerosis, Alzheimer's disease, and Huntington's disease, the composition comprising a compound of  claim 17  or a salt, solvate, or hydrate thereof, and a pharmaceutically acceptable carrier in an amount effective to antagonize a 5-HT 7  receptor. 
     
     
         19 . A method of treating a patient having a medical condition for which a 5-HT 7  antagonist is indicated, comprising the step of administering to the patient a pharmaceutical composition comprising a compound of  claim 17 . 
     
     
         20 . A method of treatment of one or more conditions selected from the group consisting of schizophrenia, psychosis, depression, Parkinsonism, amyotrophic lateral sclerosis, for treating a patient having Alzheimer's disease, and Huntington's disease the method comprising the step of administering to a patient having such condition an effective amount of a pharmaceutical composition comprising a compound of  claim 17 , or a salt, solvate, or hydrate thereof, and a pharmaceutically acceptable carrier.