2,7-substituted octahydro-1H-pyrido[1,2-A]pyrazine derivatives as ligands for serotonin receptors

Abstract

Substituted pyrido[1,2-a]pyrazines of general formula I; wherein Ar and Ar 1 represent various carbocyclic and heterocyclic aromatic rings; A represents O, S, SO, SO 2 , CHOH, C═O, or —(CR 3 R 4 ); and n is 0-2, as well as precursors thereto, are ligands for dopamine receptor subtypes and serotonin (5HT) within the body and are therefore useful in the treatment of disorders of the dopamine and serotonin systems:

1 . A method of treatment of a disease or condition which is caused by a disorder of the serotonin system which comprises administering to a mammal in need of such treatment a compound of the formula  
       
         
           
           
               
               
           
         
         wherein Ar is phenyl, naphthyl, benzoxazolonyl, indolyl, indolonyl, benzimidazolyl, quinolyl, furyl, benzofuryl, thienyl, benzothienyl, oxazolyl, benzoxazolyl;  
         Ar 1  is phenyl, pyridinyl, pyridazinyl, pyrimidinyl, pyrazinyl;  
         A is O, S, SO, SO 2 , C═O, CHOH, or —(CR 3 R 4 )—;  
         n is 0, 1 or 2;  
         each of Ar and Ar 1  may be independently and optionally substituted with one to four substituents independently selected from the group consisting of fluoro, chloro, bromo, iodo, cyano, nitro, thiocyano, —SR, —SOR, —SO 2 R, —NHSO 2 R, —(C 1 -C 6 )alkoxy, —NR 1 R 2 , —NRCOR 1 , —CONR 1 R 2 , Ph, —COR, COOR, —(C 1 -C 6 )alkyl, trifluoromethoxy, and —(C 1 -C 6 )alkyl substituted with one to six halogens, —(C 3 -C 6 )cycloalkyl, or trifluoromethoxy;  
         each and every R, R 1 , and R 2  is independently selected from the group consisting of hydrogen, —(C 1 -C 6 )alkyl, —(C 1 -C 6 )alkyl substituted with one to thirteen halogens selected from fluorine, chlorine, bromine and iodine, phenyl, benzyl, —(C 2 -C 6 )alkenyl, —(C 3 -C 6 )cycloalkyl, and —(C 1 -C 6 )alkoxy;  
         each and every R 3  and R 4  is independently selected from a group consisting of hydrogen, methyl, ethyl, n-propyl, and i-propyl; or a  
         diastereomeric or optical isomers thereof; or a  
         pharmaceutically acceptable salt thereof.