| 摘要 |
The present invention relates to certain pyrazole derivatives of Formula (I) and pharmaceutical compositions thereof that modulate the activity of the 5-HT2A serotonin receptor.;;Compounds and pharmaceutical compositions thereof are directed to methods useful in the prophylaxis or treatment of platelet aggreagation, 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, NOS schizophrenia and related disorders, and sleep disorders, sleep disorders, diabetic-related disorders and the like.;The present invention also relates to the method of prophylaxis or treatment of 5-HT2A serotonin receptor mediated disorders in combination with a dopamine D2 receptor antagonist such as haloperidol, administered separately or together. |
| 主权项 |
1. A method for modulating the activity of a 5HT2A serotonin receptor by contacting the receptor with a compound of Formula (IIa):or a pharmaceutically acceptable salt, hydrate or solvate thereof, wherein:
R1 is phenyl or naphthyl optionally substituted with R9, R10, R11, R12, R13, R14, and R15 each selected independently from the group consisting of C1-6 acyl, C1-6 alkoxy, C1-6 alkyl, amino, C1-6 alkylamino, C2-8 dialkylamino, C1-6 alkylimino, cyano, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, heterocyclic, hydroxyl, nitro, and phenyl, or two adjacent R9, R10, R11, R12, R13, R14 and R15 together with the atoms to which the are attached form a C5-7 cycloalkyl group or heterocyclic group each optionally substituted with F; and wherein said C1-6 alkyl, C1-6 alkylimino, and heterocyclic are each optionally substituted with 1 to 5 substituents selected independently from the group consisting of C1-6 alkyl, amino, C1-6 alkylamino, C2-8 dialkylamino, and hydroxyl; R2 is C1-6 alkyl; R3 is H or halogen; R4 is selected from the group consisting of H, C1-6 alkyl and C1-6 haloalkyl; R6 is selected from the group consisting of C1-6 alkoxy, C1-6 haloalkoxy, and hydroxyl, wherein said C1-6 alkoxy group is optionally substituted with 1 to 5 further substituents selected independently from the group consisting of amino C2-8 dialkylamino, carboxy, and phenyl, and wherein said amino and phenyl are each optionally substituted with 1 to 5 further substituents selected from the group consisting of halogen and carbo-C1-6-alkoxy; R6a, R6b, and R6c are each independently selected from the group consisting of H, C1-6 alkoxy, C1-6 alkyl, amino, C1-6 alkylamino, C2-8 dialkylamino, cyano, halogen, C1-6 haloalkoxy, C1-6 haloalkyl, hydroxyl, and nitro; R7 and R8 are both H; X is O; and Q is a bond. |
