Diarylamine and arylheteroarylamine pyrazole derivatives as modulators of 5ht2a

• US 20060229335A1
• Filed: 12/22/2003
• Published: 10/12/2006
• Est. Priority Date: 12/24/2002
• Status: Abandoned Application

• Current Assignee: Arena Pharmaceuticals Incorporated (Pfizer Inc.)
• Original Assignee: Arena Pharmaceuticals Incorporated (Pfizer Inc.)
• Inventors: Teegarden, Bradley, Strah-Pleynet, Sonja, Jayakumar, Honnappa
• Application Number:
  US10/540,650
• Publication Number:
  US 20060229335A1
• Time in Patent Office: Days
• US Class Current: 514/314
• CPC Class Codes: A61P 7/02 Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: C07D 231/12 with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 403/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 417/12 linked by a chain containing hetero atoms as chain links

Abstract

One aspect of the present invention relates to certain diarylamine and arylheteroarylamine pyrazole derivatives of Formula (A) and pharmaceutical compositions that modulate the activity of the human 5HT2A serotonin receptor. Compounds and pharmaceutical compositions are directed to methods useful in the prophylaxis or treatment of reducing platelet aggreagation, sleep disorders, 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 a symptom, behavioral disorders, drug induced psychosis, excitative psychosis, Gilles de la Tourette'"'"'s syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia and NOS schizophrenia and related disorders. Another aspect of the present invention is directed to the method of prophylaxis or treatment of 5HT2A serotonin receptor mediated disorders in combination with a dopamine D2 receptor antagonist such as haloperidol, administered separately or together.

Claims

1-97. -97. (canceled)

98. A compound of Formula (A):

wherein;

i) R₁ is aryl or heteroaryl each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C_1-5 acyl, C_1-5 acyloxy, C_2-6 alkenyl, C_1-4 alkoxy, C_1-6 alkyl, C_1-5 alkylcarboxamide, C_2-6 alkynyl, C_1-4 alkylsulfonamide, C_1-4 alkylsulfinyl, C_1-4 alkylsulfonyl, C_1-4 alkylthio, C_1-6 alkylureyl, amino, C_1-4 alkylamino, C_2-8 dialkylamino, carbo-C_1-6-alkoxy, carboxamide, carboxy, cyano, C_3-7 cycloalkyl, C_2-8 dialkylcarboxamide, C_2-8 dialkylsulfonamide, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, C_1-4 haloalkylsulfinyl, C_1-4 haloalkylsulfonyl, C_1-4 haloalkylthio, hydroxyl, thiol, nitro, phenoxy and phenyl; and

wherein C_2-6 alkenyl, C_1-6 alkyl and C_2-6 alkynyl substituents may be optionally substituted with 1 to 5 substituents selected independently from the group consisting of C_1-5 acyl, C_1-5 acyloxy, C_2-6 alkenyl, C_1-4 alkoxy, C_1-6 alkyl, C_1-5 alkylcarboxamide, C_2-6 alkynyl, C_1-4 alkylsulfonamide, C_1-4 alkylsulfinyl, C_1-4 alkylsulfonyl, C_1-4 alkylthio, C_1-6 alkylureyl, amino, C_1-4 alkylamino, C_2-8 dialkylamino, carbo-C_1-6-alkoxy, carboxamide, carboxy, cyano, C_3-7 cycloalkyl, C_2-8 dialkylcarboxamide, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, C_1-4 haloalkylsulfinyl, C_1-4 haloalkylsulfonyl, C_1-4 haloalkylthio, hydroxyl, thiol and nitro;

or two adjacent substituents together with the ring carbons to which they are bonded form a C_5-7 cycloalkyl optionally replaced with 1 to 2 oxygen atoms;

ii) R₂ is C_1-6 alkyl, C_2-6 alkenyl, C_2-6 alkynyl or C_3-7 cycloalkyl;

iii) R₃ is H, C_2-6 alkenyl, C_1-6 alkyl, C_1-5 alkylcarboxamide, C_2-6 alkynyl, C_1-4 alkylsulfonamide, carbo-C_1-6-alkoxy, carboxamide, carboxy, cyano, C_3-7 cycloalkyl, C_2-8 dialkylcarboxamide, halogen, heteroaryl or phenyl; and

wherein C_2-6 alkenyl, C_1-6 alkyl, C_2-6 alkynyl, C_1-4 alkylsulfonamide, C_3-7 cycloalkyl, heteroaryl or phenyl may be optionally substituted with 1 to 5 substituents selected independently from the group consisting of C_2-6 alkenyl, C_1-6 alkyl, C_1-4 alkoxy, amino, C_1-4 alkylamino, C_2-6 alkynyl, C_2-8 dialkylamino, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, hydroxyl and thiol;

iv) R_3a is selected from the group consisting of H, C_1-6 acyl, C_1-6 acyloxy, C_2-6 alkenyl, C_1-6 alkoxy, C_1-6 alkyl, C_1-6 alkylcarboxamide, C_2-6 alkynyl, C_1-6 alkylsulfonamide, C_1-6 alkylsulfinyl, C_1-6 alkylsulfonyl, C_1-6 alkylthio, C_1-6 alkylureyl, amino, C_1-6 alkylamino, C_2-8 dialkylamino, carbo-C_1-6-alkoxy, carboxamide, carboxy, cyano, C_3-7 cycloalkyl, C_2-8 dialkylcarboxamide, C_2-8 dialkylsulfonamide, halogen, C_1-6 haloalkoxy, C_1-6 haloalkyl, C_1-6 haloalkylsulfinyl, C_1-6 haloalkylsulfonyl, C_1-6 haloalkylthio, hydroxyl, thiol, nitro and sulfonamide; and

V) R₄, R_4a, R₅ and R_5a are each independently H, C_1-5 acyl, C_1-5 acyloxy, C_2-6 alkenyl, C_1-4 alkoxy, C_1-6 alkyl, C_1-5 alkylcarboxamide, C_2-6 alkynyl, C_1-4 alkylsulfonamide, C_1-4 alkylsulfinyl, C_1-4 alkylsulfonyl, C_1-4 alkylthio, C_1-6 alkylureyl, carbo-C_1-6-alkoxy, carboxamide, carboxy, cyano, C_3-7 cycloalkyl, C_2-8 dialkylcarboxamide, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, C_1-4 haloalkylsulfinyl, C_1-4 haloalkylsulfonyl, C_1-4 haloalkylthio, hydroxyl, thiol, 5 or 6 membered-heteroaryl, nitro, phenyl or NR₆R₇, and where the 5 or 6 membered-heteroaryl or phenyl is optionally substituted with a substituents selected from the group consisting of H, C_1-5 acyl, C_1-5 acyloxy, C_2-6 alkenyl, C_1-4 alkoxy, C_1-6 alkyl, C_1-5 alkylcarboxamide, C_2-6 alkynyl, C_1-4 alkylsulfonamide, C_1-4 alkylsulfinyl, C_1-4 alkylsulfonyl, C_1-4 alkylthio, C_1-6 alkylureyl, carbo-C_1-6-alkoxy, carboxamide, carboxy, cyano, C_3-7 cycloalkyl, C_2-8 dialkylcarboxamide, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, C_1-4 haloalkylsulfinyl, C_1-4 haloalkylsulfonyl, C_1-4 haloalkylthio, hydroxyl, thiol and nitro;

wherein;

R₆ and R₇ are each independently selected from the group consisting of H, C_1-6 alkyl, C_2-6 alkenyl, C_3-7 cycloalkyl, phenyl and benzyl group;

wherein each said C_1-6 alkyl, C_2-6 alkenyl, C_3-7 cycloalkyl, phenyl and benzyl group is optionally substituted with 1 to 5 substituents selected independently from the group consisting of H, C_1-5 acyl, C_2-6 alkenyl, C_1-4 alkoxy, C_1-6 alkyl, C_1-5 alkylcarboxamide, C_1-4 alkylthio, carbo-C_1-6-alkoxy, amino, C_1-4 alkylamino, C_2-8 dialkylamino, carboxamide, carboxy, cyano, C_3-7 cycloalkyl, C_2-8 dialkylcarboxamide, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, C_1-4 haloalkylsulfinyl, C_1-4 haloalkylsulfonyl, C_1-4 haloalkylthio, hydroxyl, thiol and nitro;

or

R₆ and R₇ together with the nitrogen to which they are bonded form a 5, 6 or 7 membered cyclic structure which can be saturated or unsaturated and can contain up to four heteroatoms selected from O, NR₈ or S and said cyclic structure may be optionally substituted with 1 to 5 substituents selected independently from the group consisting of H, C_1-5 acyl, C_2-6 alkenyl, C_1-4 alkoxy, C_1-6 alkyl, C_1-5 alkylcarboxamide, C_1-4 alkylthio, carbo-C_1-6-alkoxy, amino, C_1-4 alkylamino, C_2-8 dialkylamino, carboxamide, carboxy, cyano, C_3-7 cycloalkyl, C_2-8 dialkylcarboxamide, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, C_1-4 haloalkylsulfinyl, C_1-4 haloalkylsulfonyl, C_1-4 haloalkylthio, hydroxyl, thiol and nitro;

R₈ is H or C_1-6 alkyl;

or

a pharmaceutically acceptable salt, hydrate or solvate thereof.

99. The compound according to claim 98, having Formula (I):

100. The compound according to claim 98, wherein R₁ is aryl optionally substituted with 1 to 5 substituents selected independently from the group consisting of C_1-5 acyl, C_1-4 alkoxy, C_1-6 alkyl, C_1-5 alkylcarboxamide, C_1-4 alkylsulfinyl, C_1-4 alkylsulfonyl, C_1-4 alkylthio, amino, C_1-4 alkylamino, C_2-8 dialkylamino, carboxamide, carboxy, carbo-C_1-6-alkoxy, cyano, C_2-8 dialkylcarboxamide, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, hydroxyl, thiol, nitro and phenoxy;

and where C_1-6 alkyl is optionally substituted with 1 to 3 substituents selected from the group consisting of C_1-4 alkoxy, C_1-5 alkylcarboxamide, amino, C_1-4 alkylamino, C_2-8 dialkylamino, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, hydroxyl and thiol.

101. The compound according to claim 98, wherein R₁ is aryl optionally substituted with 1 to 5 substituents selected independently from the group consisting of NO₂, F, Cl, Br, I, CF₃, CF₂CF₃, OCH₃, OCH₂CH₃, OCF₃, OCF₂CF₃, SCH₃, SCH₂CH₃, S(O)CH₃, S(O)CH₂CH₃, S(O)₂CH₃, S(O)₂CH₂CH₃, CO₂H, CN, COCH₃, COCH₂CH₃, CH₃, CH₂CH₃, NHCOCH₃, CH₂OH and OC₆H₅.

102. The compound according to claim 98, wherein R₁ is phenyl optionally substituted with 1 to 5 substituents selected independently from the group consisting of NO₂, F, Cl, Br, I, CF₃, CF₂CF₃, OCH₃, OCH₂CH₃, OCF₃, OCF₂CF₃, SCH₃, SCH₂CH₃, S(O)CH₃, S(O)CH₂CH₃, S(O)₂CH₃, S(O)₂CH₂CH₃, CO₂H, CN, COCH₃, COCH₂CH₃, CH₃, CH₂CH₃, NHCOCH₃, CH₂OH and OC₆H₅.

103. The compound according to claim 98, wherein R₁ is selected from the group consisting of benzoxazolyl-2-yl, quinolin-2-yl, quinolin-3-yl, benzimidazol-2-yl, and benzothiazol-2-yl each optionally substituted with 1 to 3 substituents selected independently from the group consisting of C_1-4 alkoxy, C_1-6 alkyl, amino, C_1-4 alkylamino, C_2-8 dialkylamino, carbo-C_1-6-alkoxy, carboxamide, carboxy, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, hydroxyl, thiol and nitro.

104. The compound according to claim 103, wherein R₁ is selected from the group consisting of benzoxazol-2-yl, quinolin-2-yl, benzoimidazol-2-yl, benzothiazol-2-yl, 5-methoxy-benzothiazol-2-yl, 5-chloro-benzothiazol-2-yl, and quinolin-3-yl.

105. The compound according to claim 98, wherein R₂ is C_1-6 alkyl.

106. The compound according to claim 105 wherein R₂ is CH₃.

107. The compound according to claim 98 wherein R₃ is H, Cl, Br, CO₂CH₃, CO₂CH₂CH₃, 2-hydroxyethyl, 2-dimethylaminoethyl, 2-diethylaminoethyl, vinyl, CH₃, CH₂CH₃, phenyl, 4-methoxyphenyl, 3-methoxyphenyl, 4-fluorophenyl, 4-trifluoromthoxyphenyl, thiophenyl, CO₂H, cyclopropyl, —

CCH, —

CH═

CH—

CCH or CN.

108. The compound according to claim 107 wherein R₃ is H, Cl or Br.

109. The compound according to claim 98 wherein R₄ is H, halogen or NR₆R₇.

110. The compound according to claim 109 wherein R₄ is H, F, N(CH₃)₂, or pyrrolidin-1-yl.

111. The compound according to claim 98 wherein R₅ is H.

112. The compound according to claim 98, having Formula (II):

wherein;

R₄ is H, C_1-4 alkoxy, phenyl, halogen, 5 or 6 membered-heteroaryl, hydroxyl, thiol or NR₆R₇, where the phenyl or heteroaryl group is optionally substituted with 1 to 5 substituents independently selected from the group consisting of C_1-5 acyl, C_1-4 alkoxy, C_1-6 alkyl, C_1-5 alkylcarboxamide, C_1-4 alkylsulfonyl, C_1-4 alkylthio, amino, C_1-4 alkylamino, C_2-8 dialkylamino, cyano, C_2-8 dialkylcarboxamide, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, hydroxyl, thiol and nitro; and

wherein;

R₆ and R₇ are independently H, C_1-6 alkyl, or

R₆ and R₇ together with the nitrogen to which they are bonded form a 5, 6 or 7 membered cyclic structure that may contain up to four heteroatoms selected from O, S or N—

C_1-4 alkyl; and

R₅ is H, C_1-4 alkoxy, C_1-6 alkyl, carboxamide, carboxy, cyano, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, hydroxyl, thiol or nitro.

113. The compound according to claim 112, wherein R₄ is H, Cl, F, dimethylamino, diethylamino, pyrrolidin-1-yl, morpholin-1-yl, 4-methylpiperazin-1-yl, 4-ethylpiperazin-1-yl, hydroxyl, thiol, OCH₃ or OCH₂CH₃;

and R₅ is H or halogen.

114. The compound according to claim 98, having Formula (IVa):

wherein;

R₄ is H, or C_1-4 alkoxy; and

R₅ is H, C_1-4 alkoxy, C_1-6 alkyl, carboxamide, carboxy, cyano, halogen, C_1-4 haloalkoxy, C_1-4 haloalkyl, hydroxyl, thiol or nitro.

115. The compound according to claim 114, wherein R₄ is OCH₃, and R₅ is H.

116. The compound according to claim 98, selected from the group consisting of:

(4-Chloro-phenyl)-[3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amine;

[3-(2-Methyl-2H-pyrazol-3-yl)-phenyl]-(4-trifluoromethyl-phenyl)-amine;

[3-(2-Methyl-2H-pyrazol-3-yl)-phenyl]-(4-trifluoromethoxy-phenyl)-amine;

[3-(2-Methyl-2H-pyrazol-3-yl)-phenyl]-(3-trifluoromethoxy-phenyl)-amine;

[3-(2-Methyl-2H-pyrazol-3-yl)-phenyl]-(4-fluoro-phenyl)-amine;

(4-Chloro-phenyl)-[4-methoxy-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-amine;

(4-Chloro-phenyl)-[3-(2-isopropyl-2H-pyrazol-3-yl)-phenyl]-amine;

(4-Fluoro-phenyl)-[3-(2-isopropyl-2H-pyrazol-3-yl)-phenyl]-amine;

[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-chloro-phenyl)-amine;

[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-trifluoromethyl-phenyl)-amine;

[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-trifluoromethoxy-phenyl)-amine;

[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-trifluoromethoxy-phenyl)-amine;

[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-fluoro-phenyl)-amine;

[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-methyl-4-chloro-phenyl)-amine;

[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-chloro-4-trifluoromethyl-phenyl)-amine;

[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3,4-difluoro-phenyl)-amine;

[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-chloro-phenyl)-amine;

[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-methoxy-phenyl)-amine;

[3-(4-Chloro-2-methyl-2H-pyrazol-3-yl)4-methoxy-phenyl]-(4-chloro-phenyl)-amine;

(4-Chloro-phenyl)-[3-(4-fluoro-2-methyl-2H-pyrazol-3-yl)4-methoxy-phenyl]-amine;

(4-Chloro-phenyl)-[3-(4-fluoro-2-methyl-2H-pyrazol-3-yl)-phenyl]-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(2-nitro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-chloro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3,5-bis-trifluoromethyl-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-methoxy-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3,4-dimethoxy-phenyl)-amine;

1-{3-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenylamino]-phenyl}-ethanone;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3,5-dichloro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3,5-dimethyl-phenyl)-amine;

N-{3-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenylamino]-phenyl}-acetamide;

{3-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenylamino]-phenyl }-methanol;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(2-methyl-4-chloro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-phenoxy-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-trifluoromethyl-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-nitro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(2,3,4-trimethoxy-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-fluoro-4-methyl-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(2,4-bis-trifluoromethyl-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-fluoro-4-methoxy-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(2,3-difluoro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(2,4-difluoro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-chloro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-fluoro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-methoxy-phenyl)-amine;

Benzo[1,3]dioxol-5-yl-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-trifluoromethoxy-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-bromo-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-methylsulfanyl-phenyl)-amine;

4-[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenylamino]-benzonitrile;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-trifluoromethyl-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-trifluoromethoxy-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-methanesulfonyl-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-chloro-4-fluoro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3,4-dichloro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-methyl4-chloro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3,5-difluoro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-chloro-4-trifluoromethyl-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3,4-difluoro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(3-methyl-4-fluoro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(2-methyl-4-fluoro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(4-iodo-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(2-methoxy-5-methyl-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-5-(N,N-dimethylamino)-phenyl]-(4-chloro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-5-fluoro-phenyl]-(4-chloro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-5-pyrrolidin-1-yl-phenyl]-(4-chloro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-(4-chloro-phenyl)-amine;

[3-(4-Bromo-2-isopropyl-2H-pyrazol-3-yl)-phenyl]-(4-fluoro-phenyl)-amine;

[3-(4-Bromo-2-isopropyl-2H-pyrazol-3-yl)-phenyl]-(4-chloro-phenyl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-naphthalen-1-yl-amine; and

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-naphthalen-2-yl-amine;

Benzoxazol-2-yl-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-quinolin-2-yl-amine;

(1H-Benzoinidazol-2-yl)-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-amine;

Benzothiazol-2-yl-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(5-methoxy-benzothiazol-2-yl)-amine;

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-quinolin-3-yl -amine and

[3-(4-Bromo-2-methyl-2H-pyrazol-3-yl)-phenyl]-(5-chloro-benzothiazol-2-yl)-amine;

or

a pharmaceutically acceptable salt, hydrate or solvate thereof.

117. A pharmaceutical composition comprising a compound according to claim 98 or 116, and a pharmaceutically acceptable carrier.

118. A method for prophylaxis or treatment of reducing platelet aggregation in an individual comprising administering to said individual in need of such prophylaxis or treatment a compound according to claim 98 or 116.

119. A method for prophylaxis or treatment of reducing a risk of blood clot formation in an angioplasty or coronary bypass surgery individual, comprising administering to said individual in need of such prophylaxis or treatment a compound according to claim 98 or 116.

120. A method for prophylaxis or treatment of reducing risk of blood clot formation in an individual suffering from atrial fibrillation, comprising administering to said individual in need of such prophylaxis or treatment a compound according to claim 98 or 116.

121. A method for prophylaxis or treatment of an individual suffering from at least one of the indications selected from the group consisting of behavioral disorder, drug induced psychosis, excitative psychosis, Gilles de la Tourette'"'"'s syndrome, manic disorder, organic or NOS psychosis, psychotic disorder, psychosis, acute schizophrenia, chronic schizophrenia and NOS schizophrenia comprising administering to said individual in need of such prophylaxis or treatment a dopamine D2 receptor antagonist and a compound according to claim 98 or 116.

122. A method for prophylaxis or treatment of a sleep disorder in an individual comprising administering to said individual in need of such prophylaxis or treatment a compound according to claim 98 or 116.