Chemical compounds

Abstract

The present invention provides a compound of a formula (I): wherein the variables are defined herein; to a process for preparing such a compound; and to the use of such a compound in the treatment of a chemokine (such as CCR3) or H1 mediated disease state.

1 - 26 . (canceled)  
   
   
       27 . A compound of the following formula:  
     
       
         
         
             
             
         
       
     
     wherein: 
 X is CH 2 ,  
 R 1  is phenyl substituted with one or more of fluorine, chlorine, or C 1-4  alkyl;  
 R 3  is heterocyclyl optionally substituted by: halogen, OH, SH, NO 2 , oxo, C 1-6  alkyl {said alkyl being optionally substituted by halogen, OC(O)C 1-6  alkyl, S(O) 2 R 48 , phenyl (said phenyl being optionally substituted by halogen), C 1-6  alkyl, S(O) 2 R 38  or C(O)NR 39 R 40 ), naphthyloxy (itself optionally substituted by halo or C 2-6  alkenyl), C 3-10  cycloalkyl (itself optionally substituted by C 1-4  alkyl or oxo) or NR 41 C(O)OCH 2 (fluoren-9-yl)}, NR 41 C(O)OCH 2 (fluoren-9-yl), C 1-6  alkoxy {said alkoxy being optionally substituted by halogen, C 1-6  alkoxy, NHCO 2 (C 1-6  alkyl), CO 2 R 4 , NR 5 R 6  or phenyl (said phenyl being optionally substituted by halogen or NO 2 )}, C 1-6  alkylthio, C 1-6  haloalkylthio, C 3-10  cycloalkyl, NR 7 R 8 , NR 9 C(O)R 10 , CO 2 R 11 , C(O)NR 12 R 13 , C(O)R 14 , S(O) d R 15 , S(O) 2 NR 42 R 43 , NR 44 S(O) 2 R 45 , phenyl {said phenyl being optionally substituted by halogen, C 1-6  alkyl, C 1-6  haloalkyl, CN, NO 2 , C 1-6  alkoxy (said alkoxy being optionally substituted by halogen, OH or pyridinyl), phenyl (said phenyl being optionally substituted by halogen, C 1-6  alkyl, C 1-6  haloalkyl, CN, NO 2 , C 1-6  alkoxy or C 1-6  haloalkoxy or heterocyclyl (said heterocyclyl being optionally substituted by halogen, C 1-6  alkyl, C 1-6  haloalkyl, CN, NO 2 , C 1-6  alkoxy or C 1-6  haloalkoxy)}, heterocyclyl {said heterocyclcyl being optionally substituted by halogen, C 1-6  alkyl, C 1-6  haloalkyl, CN, NO 2 , C 1-6  alkoxy, C 1-6  haloalkoxy, phenyl (said phenyl being optionally substituted by halogen, C 1-6  alkyl, C 1-6  haloalkyl, CN, NO 2 , C 1-6  alkoxy or C 1-6  haloalkoxy)or heterocyclyl (said heterocyclyl being optionally substituted by halogen, C 1-6  alkyl, C 1-6  haloalkyl, CN, NO 2 , C 1-6  alkoxy or C 1-6  haloalkoxy)}, phenoxy {said phenoxy being optionally substituted by halogen, C 1-6  alkyl, C 1 - 6  haloalkyl, CN, NO 2 , C 1-6  alkoxy, C 1-6  haloalkoxy, phenyl (said phenyl being optionally substitued by halogen, C 1-6  alkyl, C 1-6  haloalkyl, CN, NO 2 , C 1-6  alkoxy or C 1-6  haloalkoxy) or heterocyclyl (said pheterocyclcyloptionally substituted by halogen, C 1-6  alkyl, C 1-6  haloalkyl, CN, NO 2 , C 1-6  alkoxy or C 1-6  haloalkoxy)}, SCN, CN, SO 3 H (or an alkali metal salt thereof), methylenedioxy or difluoromethylenedioxy; when aryl is phenyl adjacent substituents may join to form, together with the phenyl ring to which they are attached, a dihydrophenanthrene moiety;  
 or a pharmaceutically acceptable salt thereof; or a solvate thereof.  
 
   
   
       28 . The compound of  claim 27 , wherein the heterpcyclyl is furyl, thienyl, pyrrolyl, 2,5-dihydropyrrolyl, thiazolyl, pyrazolyl, oxazolyl, isoxazolyl, imidazolyl, piperidinyl, morpholinyl, pyridinyl, pyrimidinyl, indolyl, 2,3-dihydroindolyl, benzo[b]furyl, benz[b]thienyl, 2,3-dihydrobenz[b]thienyl, indazolyl, benzimidazolyl, benztriazolyl, benzoxazolyl, benzthiazolyl, 2,3-dihydrobenzthiazolyl, 1,2,3-benzothiadiazolyl, an imidazopyridinyl, thieno[3,2-b]pyridin-6-yl 1,2,3-benzoxadiazolyl, 2,1,3-benzothiadiazolyl, benzofurazan, quinoxalinyl, dihydro-1-benzopyryliumyl, 3,4-dihydro-1H-2,1-benzothi-azinyl, a pyrazolopyridine, a purine, quinolinyl, isoquinolinyl, a naphthyridinyl, a benzothiazinyl, benzo[d]imidazo[2,1-b]thiazol-2-yl, or dibenzothiophenyl.  
   
   
       29 . The compound of  claim 27 , wherein R 1  is aryl or substituted aryl.  
   
   
       30 . The compound of  claim 28 , wherein R 1  is aryl or substituted aryl.  
   
   
       31 . The compound of  claim 27 , wherein R 1  is phenyl substituted with one or more of fluorine, chlorine, C 1-4  alkyl or C 1-4  alkoxy.  
   
   
       32 . The compound of  claim 28 , wherein R 1  is phenyl substituted with one or more of fluorine, chlorine, C 1-4  alkyl or C 1-4  alkoxy.  
   
   
       33 . A method of treating CCR3 meidated disease comprising administering to a subject in need thereof an effective amount of the compound of claim  1 .