Ethers, secondary amines and derivatives thereof as modulators of the 5-ht 2a serotonin receptor useful for the treatment of disorders related thereto

Abstract

The present invention pertains to certain compounds 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 platelet aggreagation, coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, blood clot formation, asthma or symptoms thereof, agitation or a symptom thereof, 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, progressive multifocal leukoencephalopathy and the like. The present invention also relates to the methods for the treatment of 5-HT 2A serotonin receptor associated disorders in combination with other pharmaceutical agents administered separately or together.

1 - 46 . (canceled) 
     
     
         47 . A method for modulating the activity of a 5-HT 2A  serotonin receptor by contacting the receptor with N-[4-[2-(2-hydroxy-ethylamino)-ethoxy]-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-methoxy-benzamide, or a pharmaceutically acceptable salt thereof, comprising administering to an individual in need thereof a therapeutically effective amount of an isolated compound that is N-[4-[2-(2-hydroxy-ethylamino)-ethoxy]-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-methoxy-benzamide, or a pharmaceutically acceptable salt thereof. 
     
     
         48 . A method for treating a 5-HT 2A  serotonin associated disorder in an individual comprising administering to the individual in need thereof a therapeutically effective amount of an isolated compound that is N-[4-[2-(2-hydroxy-ethylamino)-ethoxy]-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-methoxy-benzamide, or a pharmaceutically acceptable salt thereof. 
     
     
         49 . The method according to  claim 48 , wherein said 5-HT 2A  mediated disorder is sleep disorder. 
     
     
         50 . The method according to  claim 48 , wherein said 5-HT 2A  mediated disorder is progressive multifocal leukoencephalopathy. 
     
     
         51 . The method according to  claim 48 , wherein said 5-HT 2A  mediated disorder is hypertension. 
     
     
         52 . The method according to  claim 48 , wherein said 5-HT 2A  mediated disorder is pain. 
     
     
         53 . The method according to  claim 48 , wherein said 5-HT 2A  mediated disorder is claudication. 
     
     
         54 . The method according to  claim 48 , wherein said 5-HT 2A  mediated disorder is peripheral artery disease. 
     
     
         55 . The method according to  claim 48 , wherein said 5-HT 2A  mediated disorder is vasoconstriction. 
     
     
         56 . The method according to  claim 48 , wherein said 5-HT 2A  mediated disorder is vasospasm. 
     
     
         57 . The method according to  claim 48 , wherein said 5-HT 2A  mediated disorder is thrombosis. 
     
     
         58 . A method for reducing platelet aggregation in an individual comprising administering to the individual in need thereof a therapeutically effective amount of an isolated compound that is N-[4-[2-(2-hydroxy-ethylamino)-ethoxy]-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-methoxy-benzamide, or a pharmaceutically acceptable salt thereof. 
     
     
         59 . The method of  claim 58 , wherein the individual has coronary artery disease, myocardial infarction, transient ischemic attack, angina, stroke, atrial fibrillation, or a symptom of any of the foregoing. 
     
     
         60 . The method according to  claim 59 , wherein said 5-HT 2A  mediated disorder is stroke. 
     
     
         61 . A method for reducing risk of blood clot formation in an angioplasty or coronary bypass surgery patient, or a patient suffering from atrial fibrillation, comprising administering to the individual in need thereof a therapeutically effective amount of an isolated compound that is N-[4-[2-(2-hydroxy-ethylamino)-ethoxy]-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-methoxy-benzamide, or a pharmaceutically acceptable salt thereof. 
     
     
         62 . A method for treating a 5-HT 2A  serotonin receptor associated disorder in an individual comprising administering to the individual in need thereof a therapeutically effective amount of an isolated compound that is N-[4-[2-(2-hydroxy-ethylamino)-ethoxy]-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-3-methoxy-benzamide, or a pharmaceutically acceptable salt thereof.