1-(2-phenoxymethylheteroaryl) piperidine and piperazine compounds

Abstract

The invention relates to compounds of formula I: where X, HAr, a, and R 1 through R 6 are as defined in the specification, or a pharmaceutically acceptable salt thereof. The compounds of formula I are serotonin and norepinephrine reuptake inhibitors. The invention also relates to pharmaceutical compositions comprising such compounds; methods of using such compounds; and process and intermediates for preparing such compounds.

1 . A compound of formula I: 
       
         
           
           
               
               
           
         
         where: X is —N—; HAr is a 5-7 membered heteroaryl with one or two heteroatoms selected from nitrogen, oxygen, and sulfur; a is 0 or 1; R 1  is halo or trifluoromethyl; and R 2-6  are independently hydrogen, halo, —C 1-6 alkyl, —CF 3 , —C 2-6 alkynyl, —O—C 1-6 alkyl, —OCF 3 , —C 1-4 alkylene-O—C 1-4 alkyl, —C 0-1 alkylene-phenyl, —O—C 0-3 alkylene-phenyl, —C 0-6 alkylene-OH, —CN, —COOH, —CHO, —C(O)—C 1-6 alkyl, —C(O)—C 1-4 alkyl, —CH 2 SH, —S—C 1-6 alkyl, —C 1-4 alkylene-S—C 1-4 alkyl, or —NO 2 ; wherein the phenoxymethyl group and the piperazine ring are attached to adjacent carbon atoms on HAr; or a pharmaceutically acceptable salt thereof. 
       
     
     
         2 - 4 . (canceled) 
     
     
         5 . The compound of  claim 1 , where R 2  is hydrogen or halo. 
     
     
         6 . The compound of  claim 1 , where R 3  is hydrogen or halo. 
     
     
         7 . The compound of  claim 1 , where R 4  is hydrogen or halo. 
     
     
         8 . The compound of  claim 1 , where R 5  is hydrogen or halo. 
     
     
         9 . The compound of  claim 1 , where R 6  is hydrogen or halo. 
     
     
         10 . The compound of  claim 1 , where a is 0. 
     
     
         11 . The compound of  claim 1 , where HAr is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl, 2-furyl, 4-furyl, 2-thienyl, 3-thienyl, and 4-thienyl. 
     
     
         12 . The compound of  claim 11 , where R 2-6  are independently hydrogen or halo. 
     
     
         13 - 14 . (canceled) 
     
     
         15 . A method of preparing the compound of  claim 1 , the process comprising deprotecting a compound of formula IV: 
       
         
           
           
               
               
           
         
         or a salt thereof, where P represents an amino-protecting group, to provide a compound of formula I. 
       
     
     
         16 . The method of  claim 15 , where a is 0; HAr is selected from 2-pyridyl, 3-pyridyl, 4-pyridyl, 5-pyridyl, 2-furyl, 4-furyl, 2-thienyl, 3-thienyl, and 4-thienyl; and R 2-6  are independently hydrogen or halo. 
     
     
         17 . A pharmaceutical composition comprising the compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         18 - 20 . (canceled)