Imidazo[1,2-a]pyridine derivatives as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto

Abstract

Imidazo[1,2-α]pyridine derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the 5-HT 2A serotonin receptor. Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of insomnia, dyssomnia, parasomnia and related sleep disorders, platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, thrombosis, asthma or symptoms thereof, agitation or symptoms thereof, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette's syndrome, manic disorder, organic or NOS psychosis, psychotic disorders, psychosis, acute schizophrenia, chronic schizophrenia, NOS schizophrenia and related disorders, diabetic-related disorders, progressive multifocal leukoencephalopathy and the like. The present invention also relates to methods for the treatment of 5-HT 2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.

1 .- 50 . (canceled) 
     
     
         51 . A compound selected from the group consisting of:
 (4-(2,4-Difluorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 3);   (4-(4-Fluorophenethyl)piperazin-1-yl)(2-(trifluoromethyl)imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 6);   (4-(4-Fluorophenethyl)piperazin-1-yl)(2-phenylimidazo[1,2-a]pyridin-8-yl)methanone, (Compound 9);   (4-(2-Fluoro-2-(4-fluorophenyl)ethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 10);   (4-(2-Chlorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 17);   (4-(2-Fluorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 18);   (4-(2,4-Dichlorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 19); and pharmaceutically acceptable salts, solvates, and hydrates thereof.   
     
     
         52 . The compound according to  claim 51 , wherein the compound is:
 (4-(2,4-Difluorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 3); and pharmaceutically acceptable salts, solvates, and hydrates thereof.   
     
     
         53 . The compound according to  claim 51 , wherein the compound is:
 (4-(4-Fluorophenethyl)piperazin-1-yl)(2-(trifluoromethyl)imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 6); and pharmaceutically acceptable salts, solvates, and hydrates thereof.   
     
     
         54 . The compound according to  claim 51 , wherein the compound is:
 (4-(4-Fluorophenethyl)piperazin-1-yl)(2-phenylimidazo[1,2-a]pyridin-8-yl)methanone, (Compound 9); and pharmaceutically acceptable salts, solvates, and hydrates thereof.   
     
     
         55 . The compound according to  claim 51 , wherein the compound is:
 (4-(2-Fluoro-2-(4-fluorophenyl)ethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 10); and pharmaceutically acceptable salts, solvates, and hydrates thereof.   
     
     
         56 . The compound according to  claim 51 , wherein the compound is:
 (4-(2-Chlorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 17); and pharmaceutically acceptable salts, solvates, and hydrates thereof.   
     
     
         57 . The compound according to  claim 51 , wherein the compound is:
 (4-(2-Fluorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 18); and pharmaceutically acceptable salts, solvates, and hydrates thereof.   
     
     
         58 . The compound according to  claim 51 , wherein the compound is:
 (4-(2,4-Dichlorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 19); and pharmaceutically acceptable salts, solvates, and hydrates thereof.   
     
     
         59 . The compound according to  claim 51 , wherein the compound is:
 (4-(2,4-Difluorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 3).   
     
     
         60 . The compound according to  claim 51 , wherein the compound is:
 (4-(4-Fluorophenethyl)piperazin-1-yl)(2-(trifluoromethyl)imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 6).   
     
     
         61 . The compound according to  claim 51 , wherein the compound is:
 (4-(4-Fluorophenethyl)piperazin-1-yl)(2-phenylimidazo[1,2-a]pyridin-8-yl)methanone, (Compound 9).   
     
     
         62 . The compound according to  claim 51 , wherein the compound is:
 3(4-(2-Fluoro-2-(4-fluorophenyl)ethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 10).   
     
     
         63 . The compound according to  claim 51 , wherein the compound is:
 (4-(2-Chlorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 17).   
     
     
         64 . The compound according to  claim 51 , wherein the compound is:
 (4-(2-Fluorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 18).   
     
     
         65 . The compound according to  claim 51 , wherein the compound is:
 (4-(2,4-Dichlorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 19).   
     
     
         66 . A method for treating a 5-HT 2A  mediated disorder in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound according to  claim 51 . 
     
     
         67 . The method according to  claim 66 , wherein the compound is:
 (4-(2,4-Difluorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 3).   
     
     
         68 . The method according to  claim 66 , wherein the compound is:
 (4-(4-Fluorophenethyl)piperazin-1-yl)(2-(trifluoromethyl)imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 6).   
     
     
         69 . The method according to  claim 66 , wherein the compound is:
 (4-(4-Fluorophenethyl)piperazin-1-yl)(2-phenylimidazo[1,2-a]pyridin-8-yl)methanone, (Compound 9).   
     
     
         70 . The method according to  claim 66 , wherein the compound is: 3(4-(2-Fluoro-2-(4-fluorophenyl)ethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 10). 
     
     
         71 . The method according to  claim 66 , wherein the compound is:
 (4-(2-Chlorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 17).   
     
     
         72 . The method according to  claim 66 , wherein the compound is:
 (4-(2-Fluorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 18).   
     
     
         73 . The method according to  claim 66 , wherein the compound is:
 (4-(2,4-Dichlorophenethyl)piperazin-1-yl)(imidazo[1,2-a]pyridin-8-yl)methanone, (Compound 19).