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 - 17 . (canceled) 
   
   
       18 . A compound of formula (III): 
     
       
         
         
             
             
         
       
     
     wherein
 Z is CHR d (CH 2 ) n ; or Z, R 2  and R a , together with the carbon atom to which Z and R a  are attached, form a ring; 
 R 2  is aryl or heterocyclyl; or R 2 , Z, and R a , together with the carbon atom to which Z and R a  are attached, form a ring; and 
 R a  and R b  are, independently, hydrogen or C 1-4  alkyl; or R a , Z, and R 2 , together with the carbon atom to which Z and R a  are attached, form a ring. 
 
   
   
       19 . The compound of  claim 18 , wherein R 2  is phenyl optionally substituted by halogen, cyano, hydroxy, or C 1-4  alkyl. 
   
   
       20 . The compound of  claim 18 , wherein R 2  is heterocyclyl, the heterocyclyl being selected from the group consisting of furyl, thienyl, pyrrolyl, 2,5-dihydropyrrolyl, thiazolyl, pyrazolyl, oxazolyl, isoxazolyl, imidazolyl, piperidinyl, morpholinyl, pyridinyl, dihydropyridinyl, 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, imidazopyridinyl, thieno[3,2-b]pyridin-6-yl, 1,2,3-benzoxadiazolyl, benzo[1,2,3]thiadiazolyl, 2,1,3-benzothiadiazolyl, benzofurazan, quinoxalinyl, dihydro-1-benzopyryliumyl, 3,4-dihydro-1H-2,1-benzothiazinyl, pyrazolopyridine, purine, quinolinyl, isoquinolinyl, dihydroisoquinolinyl, naphthyridinyl, dihydro[1,8]naphthyridinyl, benzothiazinyl, dihydrobenzothiazinyl, benzo[d]imidazo[2,1-b]thiazol-2-yl, dibenzothiophenyl, an N-oxide thereof, a S-oxide thereof, and a S-dioxide thereof. 
   
   
       21 . The compound of  claim 20 , wherein the heterocyclyl is selected from the group consisting of indolyl, imidazolyl, thienyl, and pyridinyl. 
   
   
       22 . A compound of formula (X): 
     
       
         
         
             
             
         
       
     
     wherein
 Z is CHR d (CH 2 ) n ; 
 L is a leaving group; 
 R 2  is aryl or heterocyclyl; and 
 R b  is hydrogen or C 1-4  alkyl. 
 
   
   
       23 . The compound of  claim 22 , wherein L is bromide, triflate, or methanesulfonate. 
   
   
       24 . The compound of  claim 22 , wherein R 2  is phenyl optionally substituted by halogen, cyano, hydroxy, or C 1-4  alkyl. 
   
   
       25 . The compound of  claim 22 , wherein R 2  is heterocyclyl, the heterocyclyl being selected from the group consisting of furyl, thienyl, pyrrolyl, 2,5-dihydropyrrolyl, thiazolyl, pyrazolyl, oxazolyl, isoxazolyl, imidazolyl, piperidinyl, morpholinyl, pyridinyl, dihydropyridinyl, 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, imidazopyridinyl, thieno[3,2-b]pyridin-6-yl, 1,2,3-benzoxadiazolyl, benzo[1,2,3]thiadiazolyl, 2,1,3-benzothiadiazolyl, benzofurazan, quinoxalinyl, dihydro-1-benzopyryliumyl, 3,4-dihydro-1H-2,1-benzothiazinyl, pyrazolopyridine, purine, quinolinyl, isoquinolinyl, dihydroisoquinolinyl, naphthyridinyl, dihydro[1,8]naphthyridinyl, benzothiazinyl, dihydrobenzothiazinyl, benzo[d]imidazo[2,1-b]thiazol-2-yl, dibenzothiophenyl, an N-oxide thereof, an S-oxide thereof, and a S-dioxide thereof. 
   
   
       26 . The compound of  claim 25 , wherein the heterocyclyl is selected from the group consisting of indolyl, imidazolyl, thienyl, and pyridinyl. 
   
   
       27 . A compound of formula (A): 
     
       
         
         
             
             
         
       
     
     wherein
 X 1  is CH 2  or C(O); 
 X is CH 2 , C(O), O, S, S(O), S(O) 2  or NR 3 ; 
 R 1  is hydrogen, C 1-6  alkyl, aryl or heterocyclyl; and 
 R c  is hydrogen or hydroxy; 
 wherein, unless stated otherwise, the foregoing aryl and heterocyclyl moieties are optionally substituted by: halogen, cyano, nitro, hydroxy, oxo, S(O) p R 4 , OC(O)NR 5 R 6 , NR 7 R 8 , NR 9 C(O)R 10 , NR 11 C(O)NR 12 R 13 , S(O) 2 NR 14 R 15 , NR 16 S(O) 2 R 17 , C(O)NR 18 R 19 , C(O)R 20 , CO 2 R 21 , NR 22 CO 2 R 23 , C 1-6  alkyl, CF 3 , C 1-6  alkoxy(C 1-6 )alkyl, C 1-6  alkoxy, OCF 3 , C 1-6  alkoxy(C 1-6 )alkoxy, C 1-6  alkylthio, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl (itself optionally substituted by C 1-4  alkyl or oxo), methylenedioxy, difluoromethylenedioxy, phenyl, phenyl(C 1-4 )alkyl, phenoxy, phenylthio, phenyl(C 1-4 )alkoxy, heterocyclyl, heterocyclyl(C 1-4 )alkyl, heterocyclyloxy or heterocyclyl(C 1-4 )alkoxy; wherein any of the immediately foregoing phenyl and heterocyclyl moieties are optionally substituted with halogen, hydroxy, nitro, S(O) q (C 1-4  alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4  alkyl), S(O) 2 N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), cyano, C 1-4  alkyl, C 1-4  alkoxy, C(O)NH 2 , C(O)NH(C 1-4  alkyl), C(O)N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), CO 2 H, CO 2 (C 1-4  alkyl), NHC(O)(C 1-4  alkyl), NHS(O) 2 (C 1-4  alkyl), C(O)(C 1-4  alkyl), CF 3  or OCF 3 ; 
 p and q are, independently, 0, 1 or 2; 
 R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 18 , R 19 , R 20 , R 21  and R 22  are, independently, hydrogen, C 1-6  alkyl (optionally substituted by halogen, hydroxy or C 3-10  cycloalkyl), CH 2 (C 2-6  alkenyl), phenyl (itself optionally substituted by halogen, hydroxy, nitro, NH 2 , NH(C 1-4  alkyl), N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), S(O) 2 (C 1-4  alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4  alkyl), S(O) 2 N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), cyano, C 1-4  alkyl, C 1-4  alkoxy, C(O)NH 2 , C(O)NH(C 1-4  alkyl), C(O)N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), CO 2 H, CO 2 (C 1-4  alkyl), NHC(O)(C 1-4  alkyl), NHS(O) 2 (C 1-4  alkyl), C(O)(C 1-4  alkyl), CF 3  or OCF 3 ) or heterocyclyl (itself optionally substituted by halogen, hydroxy, nitro, NH 2 , NH(C 1-4  alkyl), N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), S(O) 2 (C 1-4  alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4  alkyl), S(O) 2 N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), cyano, C 1-4  alkyl, C 1-4  alkoxy, C(O)NH 2 , C(O)NH(C 1-4  alkyl), C(O)N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), CO 2 H, CO 2 (C 1-4  alkyl), NHC(O)(C 1-4  alkyl), NHS(O) 2 (C 1-4  alkyl), C(O)(C 1-4  alkyl), CF 3  or OCF 3 ); 
 alternatively NR 5 R 6 , NR 7 R 8 , NR 12 R 13 , NR 14 R 15 , NR 18 R 19 , independently, form a 4-7 membered heterocyclic ring, azetidine, pyrrolidine, piperidine, azepine, morpholine or piperazine, the latter optionally substituted by C 1-4  alkyl on the distal nitrogen; 
 R 4 , R 17  and R 23  are, independently, C 1-6  alkyl (optionally substituted by halogen, hydroxy or C 3-10  cycloalkyl), CH 2 (C 2-6  alkenyl), phenyl (itself optionally substituted by halogen, hydroxy, nitro, NH 2 , NH(C 1-4  alkyl), N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), S(O) 2 (C 1-4  alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4  alkyl), S(O) 2 N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), cyano, C 1-4  alkyl, C 1-4  alkoxy, C(O)NH 2 , C(O)NH(C 1-4  alkyl), C(O)N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), CO 2 H, CO 2 (C 1-4  alkyl), NHC(O)(C 1-4  alkyl), NHS(O) 2 (C 1-4  alkyl), C(O)(C 1-4  alkyl), CF 3  or OCF 3 ) or heterocyclyl (itself optionally substituted by halogen, hydroxy, nitro, NH 2 , NH(C 1-4  alkyl), N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), S(O) 2 (C 1-4  alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4  alkyl), S(O) 2 N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), cyano, C 1-4  alkyl, C 1-4  alkoxy, C(O)NH 2 , C(O)NH(C 1-4  alkyl), C(O)N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), CO 2 H, CO 2 (C 1-4  alkyl), NHC(O)(C 1-4  alkyl), NHS(O) 2 (C 1-4  alkyl), C(O)(C 1-4  alkyl), CF 3  or OCF 3 ); and 
 R 3  is hydrogen, C 1-6  alkyl or benzyl. 
 
   
   
       28 . The compound of  claim 27 , wherein R 1  is heterocyclyl, the heterocyclyl being selected from the group consisting of furyl, thienyl, pyrrolyl, 2,5-dihydropyrrolyl, thiazolyl, pyrazolyl, oxazolyl, isoxazolyl, imidazolyl, piperidinyl, morpholinyl, pyridinyl, dihydropyridinyl, 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, imidazopyridinyl, thieno[3,2-b]pyridin-6-yl, 1,2,3-benzoxadiazolyl, benzo[1,2,3]thiadiazolyl, 2,1,3-benzothiadiazolyl, benzofurazan, quinoxalinyl, dihydro-1-benzopyryliumyl, 3,4-dihydro-1H-2,1-benzothiazinyl, pyrazolopyridine, purine, quinolinyl, isoquinolinyl, dihydroisoquinolinyl, naphthyridinyl, dihydro[1,8]naphthyridinyl, benzothiazinyl, dihydrobenzothiazinyl, benzo[d]imidazo[2,1-b]thiazol-2-yl, dibenzothiophenyl, an N-oxide thereof, an S-oxide thereof, and a S-dioxide thereof. 
   
   
       29 . The compound of  claim 28 , wherein the heterocyclyl is selected from the group consisting of indolyl, imidazolyl, thienyl, and pyridinyl. 
   
   
       30 . The compound of  claim 27 , wherein R 1  is aryl or heterocyclyl, either of which is optionally substituted with a heterocyclyl selected from the group consisting of furyl, thienyl, pyrrolyl, 2,5-dihydropyrrolyl, thiazolyl, pyrazolyl, oxazolyl, isoxazolyl, imidazolyl, piperidinyl, morpholinyl, pyridinyl, dihydropyridinyl, 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, imidazopyridinyl, thieno[3,2-b]pyridin-6-yl, 1,2,3-benzoxadiazolyl, benzo[1,2,3]thiadiazolyl, 2,1,3-benzothiadiazolyl, benzofurazan, quinoxalinyl, dihydro-1-benzopyryliumyl, 3,4-dihydro-1H-2,1-benzothiazinyl, pyrazolopyridine, purine, quinolinyl, isoquinolinyl, dihydroisoquinolinyl, naphthyridinyl, dihydro[1,8]naphthyridinyl, benzothiazinyl, dihydrobenzothiazinyl, benzo[d]imidazo[2,1-b]thiazol-2-yl, dibenzothiophenyl, an N-oxide thereof, an S-oxide thereof, and a S-dioxide thereof. 
   
   
       31 . The compound of  claim 30 , wherein R 1  is aryl or heterocyclyl, either of which is optionally substituted with a heterocyclyl selected from the group consisting of indolyl, imidazolyl, thienyl, and pyridinyl. 
   
   
       32 . The compound of  claim 27 , wherein R 1  is phenyl optionally substituted with halogen, C 1-4  alkyl or C 1-4  alkoxy. 
   
   
       33 . The compound of  claim 27 , wherein X is O. 
   
   
       34 . The compound of  claim 27 , wherein R c  is hydrogen. 
   
   
       35 . The compound of  claim 27 , wherein the compound is of formula (IV): 
     
       
         
         
             
             
         
       
     
   
   
       36 . The compound of  claim 27 , wherein the compound is of formula (V): 
     
       
         
         
             
             
         
       
     
   
   
       37 . A process of preparing a compound of formula (V) as claimed in  claim 36 , the process comprising reacting a compound of formula (VI): 
     
       
         
         
             
             
         
       
     
     with osmium tetra-oxide in the presence of N-methyl-morpholine N-oxide. 
   
   
       38 . A process of preparing a compound of formula (IV) as claimed in  claim 35 , the process comprising reacting a compound of formula (V): 
     
       
         
         
             
             
         
       
     
     with boron trihydride in tetrahydrofuran at reflux. 
   
   
       39 . A compound of formula (II): 
     
       
         
         
             
             
         
       
     
     wherein
 X is CH 2 , C(O), O, S, S(O), S(O) 2  or NR 3 ; 
 R 1  is hydrogen, C 1-6  alkyl, aryl or heterocyclyl; and 
 R c  is hydrogen or hydroxy; 
 wherein, unless stated otherwise, the foregoing aryl and heterocyclyl moieties are optionally substituted by: halogen, cyano, nitro, hydroxy, oxo, S(O) p R 4 , OC(O)NR 5 R 6 , NR 7 R 8 , NR 9 C(O)R 10 , NR 11 C(O)NR 12 R 13 , S(O) 2 NR 14 R 15 , NR 16 S(O) 2 R 17 , C(O)NR 18 R 19 , C(O)R 20 , CO 2 R 21 , NR 22 CO 2 R 23 , C 1-6  alkyl, CF 3 , C 1-6  alkoxy(C 1-6 )alkyl, C 1-6  alkoxy, OCF 3 , C 1-6  alkoxy(C 1-6 )alkoxy, C 1-6  alkylthio, C 2-6  alkenyl, C 2-6  alkynyl, C 3-10  cycloalkyl (itself optionally substituted by C 1-4  alkyl or oxo), methylenedioxy, difluoromethylenedioxy, phenyl, phenyl(C 1-4 )alkyl, phenoxy, phenylthio, phenyl(C 1-4 )alkoxy, heterocyclyl, heterocyclyl(C 1-4 )alkyl, heterocyclyloxy or heterocyclyl(C 1-4 )alkoxy; wherein any of the immediately foregoing phenyl and heterocyclyl moieties are optionally substituted with halogen, hydroxy, nitro, S(O) q (C 1-4  alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4  alkyl), S(O) 2 N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), cyano, C 1-4  alkyl, C 1-4  alkoxy, C(O)NH 2 , C(O)NH(C 1-4  alkyl), C(O)N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), CO 2 H, CO 2 (C 1-4  alkyl), NHC(O)(C 1-4  alkyl), NHS(O) 2 (C 1-4  alkyl), C(O)(C 1-4  alkyl), CF 3  or OCF 3 ; 
 p and q are, independently, 0, 1 or 2; 
 R 5 , R 6 , R 7 , R 8 , R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , R 15 , R 16 , R 18 , R 19 , R 20 , R 21  and R 22  are, independently, hydrogen, C 1-6  alkyl (optionally substituted by halogen, hydroxy or C 3-10  cycloalkyl), CH 2 (C 2-6  alkenyl), phenyl (itself optionally substituted by halogen, hydroxy, nitro, NH 2 , NH(C 1-4  alkyl), N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), S(O) 2 (C 1-4  alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4  alkyl), S(O) 2 N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), cyano, C 1-4  alkyl, C 1-4  alkoxy, C(O)NH 2 , C(O)NH(C 1-4  alkyl), C(O)N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), CO 2 H, CO 2 (C 1-4  alkyl), NHC(O)(C 1-4  alkyl), NHS(O) 2 (C 1-4  alkyl), C(O)(C 1-4  alkyl), CF 3  or OCF 3 ) or heterocyclyl (itself optionally substituted by halogen, hydroxy, nitro, NH 2 , NH(C 1-4  alkyl), N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), S(O) 2 (C 1-4  alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4  alkyl), S(O) 2 N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), cyano, C 1-4  alkyl, C 1-4  alkoxy, C(O)NH 2 , C(O)NH(C 1-4  alkyl), C(O)N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  below), CO 2 H, CO 2 (C 1-4  alkyl), NHC(O)(C 1-4  alkyl), NHS(O) 2 (C 1-4  alkyl), C(O)(C 1-4  alkyl), CF 3  or OCF 3 ); 
 alternatively NR 5 R 6 , NR 7 R 8 , NR 12 R 13 , NR 14 R 15 , NR 18 R 19 , independently, form a 4-7 membered heterocyclic ring, azetidine, pyrrolidine, piperidine, azepine, morpholine or piperazine, the latter optionally substituted by C 1-4  alkyl on the distal nitrogen; 
 R 4 , R 17  and R 23  are, independently, C 1-6  alkyl (optionally substituted by halogen, hydroxy or C 3-10  cycloalkyl), CH 2 (C 2-6  alkenyl), phenyl (itself optionally substituted by halogen, hydroxy, nitro, NH 2 , NH(C 1-4  alkyl), N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), S(O) 2 (C 1-4  alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4  alkyl), S(O) 2 N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), cyano, C 1-4  alkyl, C 1-4  alkoxy, C(O)NH 2 , C(O)NH(C 1-4  alkyl), C(O)N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), CO 2 H, CO 2 (C 1-4  alkyl), NHC(O)(C 1-4  alkyl), NHS(O) 2 (C 1-4  alkyl), C(O)(C 1-4  alkyl), CF 3  or OCF 3 ) or heterocyclyl (itself optionally substituted by halogen, hydroxy, nitro, NH 2 , NH(C 1-4  alkyl), N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), S(O) 2 (C 1-4  alkyl), S(O) 2 NH 2 , S(O) 2 NH(C 1-4  alkyl), S(O) 2 N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), cyano, C 1-4  alkyl, C 1-4  alkoxy, C(O)NH 2 , C(O)NH(C 1-4  alkyl), C(O)N(C 1-4  alkyl) 2  (and these alkyl groups optionally join to form a ring as described for R 5  and R 6  above), CO 2 H, CO 2 (C 1-4  alkyl), NHC(O)(C 1-4  alkyl), NHS(O) 2 (C 1-4  alkyl), C(O)(C 1-4  alkyl), CF 3  or OCF 3 ); and 
 R 3  is hydrogen, C 1-6  alkyl or benzyl. 
 
   
   
       40 . The compound of  claim 39 , wherein R 1  is heterocyclyl, the heterocyclyl being selected from the group consisting of furyl, thienyl, pyrrolyl, 2,5-dihydropyrrolyl, thiazolyl, pyrazolyl, oxazolyl, isoxazolyl, imidazolyl, piperidinyl, morpholinyl, pyridinyl, dihydropyridinyl, 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, imidazopyridinyl, thieno[3,2-b]pyridin-6-yl, 1,2,3-benzoxadiazolyl, benzo[1,2,3]thiadiazolyl, 2,1,3-benzothiadiazolyl, benzofurazan, quinoxalinyl, dihydro-1-benzopyryliumyl, 3,4-dihydro-1H-2,1-benzothiazinyl, pyrazolopyridine, purine, quinolinyl, isoquinolinyl, dihydroisoquinolinyl, naphthyridinyl, dihydro[1,8]naphthyridinyl, benzothiazinyl, dihydrobenzothiazinyl, benzo[d]imidazo[2,1-b]thiazol-2-yl, dibenzothiophenyl, an N-oxide thereof, an S-oxide thereof, and a S-dioxide thereof. 
   
   
       41 . The compound of  claim 40 , wherein the heterocyclyl is selected from the group consisting of indolyl, imidazolyl, thienyl, and pyridinyl. 
   
   
       42 . The compound of  claim 39 , wherein R 1  is aryl or heterocyclyl, either of which is optionally substituted with a heterocyclyl selected from the group consisting of furyl, thienyl, pyrrolyl, 2,5-dihydropyrrolyl, thiazolyl, pyrazolyl, oxazolyl, isoxazolyl, imidazolyl, piperidinyl, morpholinyl, pyridinyl, dihydropyridinyl, 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, imidazopyridinyl, thieno[3,2-b]pyridin-6-yl, 1,2,3-benzoxadiazolyl, benzo[1,2,3]thiadiazolyl, 2,1,3-benzothiadiazolyl, benzofurazan, quinoxalinyl, dihydro-1-benzopyryliumyl, 3,4-dihydro-1H-2,1-benzothiazinyl, pyrazolopyridine, purine, quinolinyl, isoquinolinyl, dihydroisoquinolinyl, naphthyridinyl, dihydro[1,8]naphthyridinyl, benzothiazinyl, dihydrobenzothiazinyl, benzo[d]imidazo[2,1-b]thiazol-2-yl, dibenzothiophenyl, an N-oxide thereof, an S-oxide thereof, and a S-dioxide thereof. 
   
   
       43 . The compound of  claim 42 , wherein R 1  is aryl or heterocyclyl, either of which is optionally substituted with a heterocyclyl selected from the group consisting of indolyl, imidazolyl, thienyl, and pyridinyl. 
   
   
       44 . The compound of  claim 39 , wherein R 1  is phenyl optionally substituted with halogen, C 1-4  alkyl or C 1-4  alkoxy. 
   
   
       45 . The compound of  claim 39 , wherein X is O. 
   
   
       46 . The compound of  claim 39 , wherein R c  is hydrogen. 
   
   
       47 . A process of preparing a compound of formula (II) as claimed in  claim 39 , the process comprising reacting a compound of formula (IV): 
     
       
         
         
             
             
         
       
     
     with lead tetra-acetate in the presence of sodium carbonate in dichloromethane.