Pyrazole derivatives as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto

Abstract

Pyrazole derivatives of Formula (Ia) and pharmaceutical compositions thereof that modulate the activity of the serotonin 5HT 2A receptor. Formula (Ia). Compounds and pharmaceutical compositions thereof are directed to methods useful in the treatment of insomnia and related sleep disorders, platelet aggregation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, reducing the risk of blood clot formation, 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 the methods for the treatment of 5-IIT 2A serotonin receptor mediated disorders in combination with other pharmaceutical agents administered separately or together.

1 . A compound of Formula (Ia): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate or hydrate thereof; 
       
       wherein:
 R 1  and R 2  are each independently selected from the group consisting of H, C 1 -C 6  alkyl, C 1 -C 6  alkylaryl, aryl, C 3 -C 7  cycloalkyl, C 1 -C 6  haloalkyl, halogen, heteroaryl, and nitro; and wherein C 1 -C 6  alkyl, aryl and heteroaryl are optionally substituted with 1, 2, 3, 4 or 5 substituents selected independently from the group consisting of C 1 -C 6  acyl, C 1 -C 6  acyloxy, C 2 -C 6  alkenyl, C 1 -C 6  alkoxy, C 1 -C 6  alkyl, C 1 -C 6  alkylcarboxamide, C 1 -C 6  alkylsulfonamide, C 1 -C 6  alkylsulfinyl, C 1 -C 6  alkylsulfonyl, C 1 -C 6  alkylthio, C 1 -C 6  alkylureyl, C 1 -C 6  alkylamino, C 2 -C 6  alkynyl, amino, carbo-C 1 -C 6 -alkoxy, carboxamide, carboxy, cyano, C 3 -C 7  cycloalkyl, C 2 -C 6  dialkylamino, C 2 -C 6  dialkylcarboxamide, C 2 -C 6  dialkylsulfonamide, C 1 -C 6  haloalkoxy, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkylsulfinyl, C 1 -C 6  haloalkylsulfonyl, C 1 -C 6  haloalkylthio, halogen, hydroxyl, nitro, sulfonamide and thiol; or 
 R 1  and R 2  together with the carbon atoms to which they are bonded form a C 3 -C 7  carbocyclyl or a C 3 -C 7  heterocyclyl group each optionally substituted with 1, 2, 3, 4 or 5 substituents selected independently from the group consisting of C 1 -C 6  acyl, C 1 -C 6  acyloxy, C 2 -C 6  alkenyl, C 1 -C 6  alkoxy, C 1 -C 6  alkyl, C 1 -C 6  alkylcarboxamide, C 1 -C 6  alkylsulfonamide, C 1 -C 6  alkylsulfinyl, C 1 -C 6  alkylsulfonyl, C 1 -C 6  alkylthio, C 1 -C 6  alkylureyl, C 1 -C 6  alkylamino, C 2 -C 6  alkynyl, amino, carbo-C 1 -C 6 -alkoxy, carboxamide, carboxy, cyano, C 3 -C 7  cycloalkyl, C 2 -C 6  dialkylamino, C 2 -C 6  dialkylcarboxamide, C 2 -C 6  dialkylsulfonamide, C 1 -C 6  haloalkoxy, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkylsulfinyl, C 1 -C 6  haloalkylsulfonyl, C 1 -C 6  haloalkylthio, halogen, hydroxyl, nitro, oxo, sulfonamide and thiol; 
 R 3  is selected from the group consisting of H, C 1 -C 6  alkyl and aryl; and wherein aryl is optionally substituted with 1, 2, 3, 4 or 5 substituents selected independently from the group consisting of C 1 -C 6  acyl, C 1 -C 6  acyloxy, C 2 -C 6  alkenyl, C 1 -C 6  alkoxy, C 1 -C 6  alkyl, C 1 -C 6  alkylcarboxamide, C 1 -C 6  alkylsulfonamide, C 1 -C 6  alkylsulfinyl, C 1 -C 6  alkylsulfonyl, C 1 -C 6  alkylthio, C 1 -C 6  alkylureyl, C 1 -C 6  alkylamino, C 2 -C 6  alkynyl, amino, carbo-C 1 -C 6 -alkoxy, carboxamide, carboxy, cyano, C 3 -C 7  cycloalkyl, C 2 -C 6  dialkylamino, C 2 -C 6  dialkylcarboxamide, C 2 -C 6  dialkylsulfonamide, C 1 -C 6  haloalkoxy, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkylsulfinyl, C 1 -C 6  haloalkylsulfonyl, C 1 -C 6  haloalkylthio, halogen, hydroxyl, nitro, sulfonamide and thiol; 
 A and X are each —CH 2 CH 2 —, each optionally substituted with 1, 2, 3 or 4 substituents selected independently from the group consisting of C 1 -C 4  alkoxy, C 1 -C 3  alkyl, carboxy, cyano, C 1 -C 3  haloalkyl, halogen, hydroxyl and oxo; 
 J is —CH 2 CH 2 — or —C(═NOMe)CH 2 — each optionally substituted with 1, 2, 3 or 4 substituents selected independently from the group consisting of C 1 -C 4  alkoxy, C 1 -C 3  alkyl, carboxy, cyano, C 1 -C 3  haloalkyl, halogen, hydroxyl and oxo; and 
 Ar is aryl or heteroaryl each optionally substituted with 1, 2, 3, 4 or 5 substituents selected independently from the group consisting of C 1 -C 6  acyl, C 1 -C 6  acyloxy, C 2 -C 6  alkenyl, C 1 -C 6  alkoxy, C 1 -C 6  alkyl, C 1 -C 6  alkylcarboxamide, C 1 -C 6  alkylsulfonamide, C 1 -C 6  alkylsulfinyl, C 1 -C 6  alkylsulfonyl, C 1 -C 6  alkylthio, C 1 -C 6  alkylureyl, C 1 -C 6  alkylamino, C 2 -C 6  alkynyl, amino, carbo-C 1 -C 6 -alkoxy, carboxamide, carboxy, cyano, C 3 -C 7  cycloalkyl, C 2 -C 6  dialkylamino, C 2 -C 6  dialkylcarboxamide, C 2 -C 6  dialkylsulfonamide, C 1 -C 6  haloalkoxy, C 1 -C 6  haloalkyl, C 1 -C 6  haloalkylsulfinyl, C 1 -C 6  haloalkylsulfonyl, C 1 -C 6  haloalkylthio, halogen, C 3 -C 7  heterocyclyl, hydroxyl, nitro, sulfonamide and thiol; provided that said compound is other than: 
 1-(4-(1H-pyrazole-3-carbonyl)piperazin-1-yl)-2-(4-fluoro-1H-indol-3-yl)ethane-1,2-dione. 
 
     
     
         2 . (canceled) 
     
     
         3 . The compound according to  claim 1 , having Formula (Ie): 
       
         
           
           
               
               
           
         
       
     
     
         4 .- 23 . (canceled) 
     
     
         24 . The compound according to  claim 1 , having Formula (Ie): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate or hydrate thereof; 
       
       wherein:
 R 1  is H, halogen or C 1 -C 6  alkylaryl; 
 R 2  is H, C 1 -C 6  alkyl, aryl, C 3 -C 7  cycloalkyl, C 1 -C 6  haloalkyl, heteroaryl, or nitro; or 
 R 1  and R 2  together with the carbon atoms to which they are bonded form a C 3 -C 7  carbocyclyl; 
 R 3  is H, C 1 -C 6  alkyl, aryl, or aryl substituted with C 1 -C 6  alkoxy; 
 A and X are each —CH 2 CH 2 —, each optionally substituted with C 1 -C 3  alkyl; 
 J is —CH 2 CH 2 — optionally substituted with 1, 2, 3 or 4 substituents selected independently from the group consisting of C 1 -C 3  alkyl, hydroxyl, oxo and ═NO—C 1 -C 3  alkyl; and 
 Ar is aryl or heteroaryl each optionally substituted with 1, 2, 3, 4 or 5 substituents selected independently from the group consisting of C 1 -C 6  alkoxy, C 1 -C 6  alkylsulfonyl, C 1 -C 6  haloalkoxy, C 1 -C 6  haloalkyl, halogen and heterocyclyl. 
 
     
     
         25 . The compound according to  claim 1 , having Formula (Ie): 
       
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt, solvate or hydrate thereof; 
       
       wherein:
 R 1  is H, fluoro, chloro, bromo, iodo or 2-methylphenyl; 
 R 2  is H, methyl, ethyl, isopropyl, t-butyl, phenyl, cyclopropyl, trifluoromethyl, furan-2-yl or nitro; or 
 R 1  and R 2  together with the carbon atoms to which they are bonded form a C 5  carbocyclyl 
 R 3  is H, methyl, ethyl, t-butyl, phenyl or 4-methoxyphenyl; 
 A and X are each independently —CH 2 CH 2 — or —CH(CH 3 )CH 2 —; 
 J is —CH 2 CH 2 —, —C(═NOMe)CH 2 —, —C═OCH 2 —, —CH(CH 3 )CH 2 —, —C(CH 3 ) 2 CH 2 —, or —CHOHCH 2 —; and 
 Ar is naphthyl, 2-methoxyphenyl, 4-methoxyphenyl, 4-methanesulfonylphenyl, 4-trifluoromethoxyphenyl, 4-trifluoromethylphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,4-difluorophenyl, 3,4-difluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl and 6-chloro-1,3-dihydro-indol-2-one. 
 
     
     
         26 . The compound according to  claim 1  selected from the group consisting of:
 2-[4-(1,5-Dimethyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{4-[2-(4-chloro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 1-(4-Fluoro-phenyl)-2-[4-(2-methyl-5-phenyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone; 
 2-[4-(4-Bromo-2,5-dimethyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 5-{2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethyl}-6-chloro-1,3-dihydro-indol-2-one; 
 2-[(S)-4-(4-Chloro-1-methyl-1H-pyrazole-3-carbonyl)-3-methyl-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 2-[4-(4-Chloro-1-ethyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{4-[2-(2-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 2-[(S)-4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-3-methyl-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 2-[4-(4-Chloro-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 1-(4-Fluoro-phenyl)-2-[4-(1,4,5,6-tetrahydro-cyclopentapyrazole-3-carbonyl)-piperazin-1-yl]-ethanone; 
 2-[(R)-4-(4-Chloro-1-methyl-1H-pyrazole-3-carbonyl)-2-methyl-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(3-fluoro-phenyl)-ethanone; 
 2-[(R)-4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-2-methyl-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 (4-Chloro-1-ethyl-1H-pyrazol-3-yl)-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 2-[4-(1-tert-Butyl-5-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-pyrrolidin-1-yl-phenyl)-ethanone; 
 1-(4-Fluoro-phenyl)-2-{4-[1-(4-methoxy-phenyl)-5-phenyl-1H-pyrazole-3-carbonyl]-piperazin-1-yl}-ethanone; 
 2-[4-(5-tert-Butyl-2-methyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 (4-Chloro-1-methyl-1H-pyrazol-3-yl)-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{4-[2-(4-methoxy-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-methanesulfonyl-phenyl)-ethanone; 
 (4-Chloro-1-methyl-1H-pyrazol-3-yl)-{4-[2-(2-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone O-methyl-oxime; 
 (4-Bromo-2,5-dimethyl-2H-pyrazol-3-yl)-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 1-(4-Fluoro-phenyl)-2-[4-(1-methyl-4-o-tolyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-trifluoromethoxy-phenyl)-ethanone; 
 2-[4-(4-Chloro-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(3-fluoro-phenyl)-ethanone; 
 1-(4-Fluoro-phenyl)-2-[4-(5-methyl-2-phenyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone; 
 (4-Bromo-2-methyl-2H-pyrazol-3-yl)-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 2-[4-(5-Cyclopropyl-4-fluoro-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-trifluoromethyl-phenyl)-ethanone; 
 (4-Chloro-1-methyl-1H-pyrazol-3-yl)-{4-[2-(3-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 1-(4-Fluoro-phenyl)-2-[4-(1-methyl-5-trifluoromethyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 2-[4-(5-Ethyl-4-fluoro-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{4-[2-(3-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 2-[4-(4-Chloro-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-chloro-phenyl)-ethanone; 
 2-[4-(4-Chloro-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 {4-[2-(4-Fluoro-phenyl)-ethyl]-piperazin-1-yl}-(2-methyl-2H-pyrazol-3-yl)-methanone; 
 2-[4-(4-Fluoro-5-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-(4-phenethyl-piperazin-1-yl)-methanone; 
 (4-Chloro-1-methyl-1H-pyrazol-3-yl)-{4-[2-(4-chloro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 1-(4-Fluoro-phenyl)-2-[4-(5-isopropyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone; 
 (4-Chloro-1,5-dimethyl-1H-pyrazol-3-yl)-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 1-(4-Fluoro-phenyl)-2-[4-(4-iodo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(3,4-difluoro-phenyl)-ethanone; 
 5-{2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-acetyl}-6-chloro-1,3-dihydro-indol-2-one; 
 1-(4-Fluoro-phenyl)-2-[4-(5-methyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone 
 (4-Bromo-1,5-dimethyl-1H-pyrazol-3-yl)-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 2-[4-(4-Bromo-5-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 (4-Bromo-1,5-dimethyl-1H-pyrazol-3-yl)-{(S)-4-[2-(4-fluoro-phenyl)-ethyl]-3-methyl-piperazin-1-yl}-methanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{(S)-4-[2-(4-fluoro-phenyl)-ethyl]-2-methyl-piperazin-1-yl}-methanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{4-[2-(2-chloro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 {4-[2-(4-Fluoro-phenyl)-ethyl]-piperazin-1-yl}-(5-isopropyl-2H-pyrazol-3-yl)-methanone; 
 2-[4-(4-Chloro-5-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{(S)-4-[2-(4-fluoro-phenyl)-ethyl]-3-methyl-piperazin-1-yl}-methanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{(R)-4-[2-(4-fluoro-phenyl)-ethyl]-2-methyl-piperazin-1-yl}-methanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{4-[2-(3-chloro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 (1,5-Dimethyl-1H-pyrazol-3-yl)-{4-[2-(4-fluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 2-[4-(4-Chloro-1,5-dimethyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 (4-Chloro-1-methyl-1H-pyrazol-3-yl)-{4-[2-(4-fluoro-phenyl)-2-methyl-propyl]-piperazin-1-yl}-methanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-naphthalen-2-yl-ethanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(2-methoxy-phenyl)-ethanone; 
 1-(4-Fluoro-phenyl)-2-[4-(5-furan-2-yl-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone; 
 {4-[2-(4-Fluoro-phenyl)-ethyl]-piperazin-1-yl}-(5-methyl-1H-pyrazol-3-yl)-methanone 
 2-[4-(4-Bromo-1,5-dimethyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 (4-Chloro-1-methyl-1H-pyrazol-3-yl)-{4-[2-(4-fluoro-phenyl)-propyl]-piperazin-1-yl}-methanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-chloro-phenyl)-ethanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(2-fluoro-phenyl)-ethanone; 
 1-(4-Fluoro-phenyl)-2-[4-(1-methyl-5-phenyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone; 
 (4-Bromo-1,5-dimethyl-1H-pyrazol-3-yl)-{(R)-4-[2-(4-fluoro-phenyl)-ethyl]-3-methyl-piperazin-1-yl}-methanone; 
 1-(4-Fluoro-phenyl)-2-[4-(1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{(R)-4-[2-(4-fluoro-phenyl)-ethyl]-3-methyl-piperazin-1-yl}-methanone; 
 1-(4-Fluoro-phenyl)-2-[4-(5-nitro-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-ethanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{4-[2-(4-fluoro-phenyl)-2-hydroxy-ethyl]-piperazin-1-yl}-methanone; 
 2-[(S)-4-(4-Bromo-1,5-dimethyl-1H-pyrazole-3-carbonyl)-2-methyl-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 2-[4-(2-Ethyl-5-methyl-2H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 2-[(S)-4-(4-Chloro-1-methyl-1H-pyrazole-3-carbonyl)-2-methyl-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(2,4-difluoro-phenyl)-ethanone; 
 2-[(S)-4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-2-methyl-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone; 
 {4-[2-(4-Fluoro-phenyl)-ethyl]-piperazin-1-yl}-(1-methyl-5-trifluoromethyl-1H-pyrazol-3-yl)-methanone; 
 (4-Bromo-1-methyl-1H-pyrazol-3-yl)-{4-[2-(2,4-difluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; and 
 (4-Chloro-1-methyl-1H-pyrazol-3-yl)-{4-[2-(2,4-difluoro-phenyl)-ethyl]-piperazin-1-yl}-methanone; 
 or a pharmaceutically acceptable salt, hydrate or solvate thereof. 
 
     
     
         27 . A pharmaceutical composition comprising a compound according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         28 . 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 1 . 
     
     
         29 . The method according to  claim 28 , wherein said 5-HT 2A  mediated disorder is selected from the group consisting of coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, and atrial fibrillation. 
     
     
         30 . A method for treating a sleep disorder in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         31 . The method according to  claim 30 , wherein said sleep disorder is a dyssomnia. 
     
     
         32 . The method according to  claim 30 , wherein said sleep disorder is insomnia. 
     
     
         33 . The method according to  claim 30 , wherein said sleep disorder is a parasomnia. 
     
     
         34 . A method for increasing slow wave sleep in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         35 . A method for improving sleep consolidation in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         36 . A method for improving sleep maintenance in an individual comprising administering to said individual in need thereof a therapeutically effective amount of a compound according to  claim 1 . 
     
     
         37 .- 79 . (canceled) 
     
     
         80 . A process for preparing a composition comprising admixing a compound according to  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         81 . The compound according to  claim 1  selected from the following compound and pharmaceutically acceptable salts, hydrates, and solvates thereof:
 2-[(S)-4-(4-Chloro-1-methyl-1H-pyrazole-3-carbonyl)-3-methyl-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone. 
 
     
     
         82 . The compound according to  claim 1  selected from the following compound and pharmaceutically acceptable salts, hydrates, and solvates thereof:
 2-[(S)-4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-3-methyl-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone. 
 
     
     
         83 . The compound according to  claim 1  selected from the following compound and pharmaceutically acceptable salts, hydrates, and solvates thereof:
 2-[4-(4-Chloro-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone. 
 
     
     
         84 . The compound according to  claim 1  selected from the following compound and pharmaceutically acceptable salts, hydrates, and solvates thereof:
 2-[4-(4-Bromo-1-methyl-1H-pyrazole-3-carbonyl)-piperazin-1-yl]-1-(4-fluoro-phenyl)-ethanone.