5-HT receptor ligands and uses thereof

Abstract

Compounds of Formula (IA) that act as 5-HT receptor ligands and their uses in the treatment of diseases linked to the activation of 5-HT 2 receptors in animals are described herein.

1 - 54 . (canceled).  
     
     
         55 . A compound of Formula (IC)  
       
         
           
           
               
               
           
         
       
       wherein 
 Y is N;  
 X and Z are each independently CR, where R for each occurrence is hydrogen, halogen, (C 1 -C 4 )alkyl, amino, or (C 1 -C 4 )alkylamino;  
 W is oxy, thio, amino, (C 1 -C 4 )alkylamino, or acetylamino;  
 Q is a heteroaryl group selected from the group consisting of pyridin-2-yl, pyridin-3-yl, furan-3-yl, furan-2-yl, thiophen-2-yl, thiophen-3-yl, thiazol-2-yl, pyrrol-2-yl, pyrrol-3-yl, pyrazol-3-yl, quinolin-2-yl, quinolin-3-yl, isoquinolin-3-yl, benzofuran-2-yl, benzofuran-3-yl, isobenzofuran-3-yl, benzothiophen-2-yl, benzothiophen-3-yl, indol-2-yl, indol-3-yl, 2H-imidazol-2-yl, oxazol-2-yl, isoxazol-3-yl, 1,2,4-oxadiazol-3-yl, 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl, 1,3,4-oxadiazol-5-yl, 1,2,4-triazol-3-yl, 1,2,3-thiadiazol-4-yl, 1,2,3-thiadiazol-5-yl, 1,3,4-thiadiazol-2-yl, 1,3,4-thiadiazol-5-yl, and 1,2,4-oxathiazol-3-yl, where the heteroaryl group is optionally substituted with one to three substituents independently selected from halo, (C 1 -C 4 )alkyl, cyano, nitro, amino, (C 1 -C 4 )alkylamino, or (C 1 -C 4 )alkyoxy;  
 R 2a  and R 2b  are each independently hydrogen, (C 1 -C 4 )alkyl, or partially or fully saturated (C 3 -C 6 )cycloalkyl;  
 R 3a  and R 3b  are each independently hydrogen, halogen, (C 1 -C 4 )alkyl, or (C 1 -C 4 )alkyl substituted with hydroxy, fluoro, or (C 1 -C 4 )alkoxy;  
 R 4  is hydrogen, hydroxy, (C 1 -C 4 )alkyl, (C 1 -C 4 )alkyl substituted with hydroxy or cyano, (C 1 -C 4 )alkylcarbonyl, (C 1 -C 4 )alkoxy, (C 1 -C 4 )alkoxy-carbonyl, or (C 3 -C 4 )alkenyl;  
 a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.  
 
     
     
         56 . The compound of  claim 55  selected from the group consisting of 
 6′-(pyridin-3-ylmethoxy)-3,4,5,6-tetrahydro-2 H-[1,2′]bipyrazinyl;    2-methyl-6′-(pyridin-3-ylmethoxy)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl;    6′-(thiophen-3-ylmethoxy)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl;    6′-([1,2,3]thiadiazol-4-ylmethoxy)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl;    6′-(6-fluoro-pyridin-2-ylmethoxy)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl;    2-methyl-6′-(6-methyl-pyridin-2-ylmethoxy)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl;    6′-(6-methyl-pyridin-2-ylmethoxy)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl; and    6′-(6-chloro-pyridin-2-ylmethoxy)-3,4,5,6-tetrahydro-2H-[1,2′]bipyrazinyl;    a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.    
     
     
         57 . A method for treating or preventing a 5-HT 2  receptor-mediated disease, condition, or disorder in an animal comprising the step of administering to said animal a therapeutically effective amount of a compound of  claim 55  or  56 , a nitrogen oxide thereof, a prodrug of said compound or said nitrogen oxide; a pharmaceutically acceptable salt of said compound, said nitrogen oxide, or said prodrug, or a solvate or hydrate of said compound, said nitrogen oxide, said prodrug, or said salt.  
     
     
         58 . The method of  claim 57  wherein said 5-HT 2  receptor-mediated disease, condition or disorder is a 5-HT 2C  receptor-mediated disease, condition or disorder.  
     
     
         59 . The method of  claim 57  wherein said 5-HT 2  receptor-mediated disease, condition, or disorder is selected from the group consisting of weight loss, obesity, bulimia, premenstrual syndrome or late luteal phase syndrome, depression, atypical depression, bipolar disorders, psychoses, schizophrenia, migraine, alcoholism, tobacco abuse, panic disorder, anxiety, post-traumatic syndrome, memory loss, dementia of aging, social phobia, attention deficit hyperactivity disorder, disruptive behavior disorders, impulse control disorders, borderline personality disorder, obsessive compulsive disorder, chronic fatigue syndrome, sexual dysfunction in males, sexual dysfunction in females, anorexia nervosa, disorders of sleep, autism, seizure disorders, epilepsy, mutism, spinal cord injury, damage of the central nervous system, cardiovascular disorders, gastrointestinal disorders, diabetes insipidus, and type II diabetes.  
     
     
         60 - 67 . (canceled).