Heterocyclo-alkylsulfonyl pyrazole derivatives as anti-inflammatory/analgesic agents

Abstract

The present invention relates to compounds of the formula wherein R 2 , R 3 , R 6 and A are defined as in the specification, to pharmaceutical compositions containing them and to their medicinal use. The compounds of the invention are useful in the treatment or alleviation of inflammation and other inflammation associated disorders, such as osteoarthritis, rheumatoid arthritis, colon cancer and Alzheimer's disease, in mammals (preferably humans, dogs, cats and livestock).

1 . A compound of the formula  
       
         
           
           
               
               
           
         
       
       wherein A is a heterocycle selected from the group consisting of  
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         R 2  is hydrogen, halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-(C═O)—, formyl, formamidyl, cyano, nitro, HO—(C═O)—, (C 1 -C 6 )alkoxycarbonyl, aminocarbonyl, N—(C 1 -C 6 )alkylaminocarbonyl, N,N—[(C 1 -C 6 )alkyl] 2 aminocarbonyl, N—(C 6 -C 10 )arylaminocarbonyl, N,N—[(C 6 -C 10 )aryl] 2 aminocarbonyl, N—(C 1 -C 6 )alkyl-N—(C 6 -C 10 )arylaminocarbonyl, (C 6 -C 10 )aryl, (C 6 -C 10 )aryloxy, (C 2 -C 9 )heteroaryl, (C 2 -C 9 )heteroaryloxy, morpholino-carbonyl, (C 1 -C 6 )alkoxyaminocarbonyl or (C 1 -C 6 )alkyl-carbonylamino;  
         wherein said R 2  (C 1 -C 6 )alkyl group may optionally be substituted with one to three substitutents independently selected from halo, hydroxy, (C 1 -C 6 )alkoxy, cyano, nitro, HO—(C═O)—, (C 1 -C 6 )alkoxycarbonyl, aminocarbonyl, N—(C 1 -C 6 )alkylaminocarbonyl, N,N—[(C 1 -C 6 )alkyl] 2 aminocarbonyl, N—(C 6 -C 10 )arylaminocarbonyl, N,N—[(C 6 -C 10 )aryl] 2 aminocarbonyl, N—(C 1 -C 6 )alkyl-N—(C 6 -C 10 )arylaminocarbonyl, (C 6 -C 10 )aryl, (C 6 -C 10 )aryloxy, (C 2 -C 9 )heteroaryl, (C 2 -C 9 )heteroaryloxy, morpholino-carbonyl, (C 1 -C 6 )alkoxyaminocarbonyl or (C 1 -C 6 )alkyl-carbonylamino;  
         R 3  is hydrogen, halo, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-(C═O)—, formyl, formamidyl, cyano, nitro, —CO 2 H, (C 1 -C 6 )alkoxycarbonyl, aminocarbonyl, N—(C 1 -C 6 )alkylaminocarbonyl, N,N—[(C 1 -C 6 )alkyl] 2 aminocarbonyl, N—(C 6 -C 10 )arylaminocarbonyl, N,N—[(C 6 -C 10 )aryl] 2 aminocarbonyl, N—(C 1 -C 6 )alkyl-N—(C 6 -C 10 )arylaminocarbonyl, (C 6 -C 10 )aryl, (C 6 -C 10 )aryloxy, (C 2 -C 9 )heteroaryl, (C 2 -C 9 )heteroaryloxy, morpholino-carbonyl, (C 1 -C 6 )alkoxyaminocarbonyl or (C 1 -C 6 )alkyl-carbonylamino;  
         wherein said R 3  (C 1 -C 6 )alkyl group may optionally be substituted with one to three substitutents independently selected from halo, hydroxy, (C 1 -C 6 )alkoxy, cyano, nitro, HO—(C═O)—, (C 1 -C 6 )alkoxycarbonyl, aminocarbonyl, N—(C 1 -C 6 )alkylaminocarbonyl, N,N—[(C 1 -C 6 )alkyl] 2 aminocarbonyl, N—(C 6 -C 10 )arylaminocarbonyl, N,N—[(C 6 -C 10 )aryl] 2 aminocarbonyl, N—(C 1 -C 6 )alkyl-N—(C 6 -C 10 )arylaminocarbonyl, (C 6 -C 10 )aryl, (C 6 -C 10 )aryloxy, (C 2 -C 9 )heteroaryl, (C 2 -C 9 )heteroaryloxy, morpholino-carbonyl, (C 1 -C 6 )alkoxyaminocarbonyl or (C 1 -C 6 )alkyl-carbonylamino;  
         R 4  is (C 1 -C 6 ) alkyl optionally substituted by one to three halo atoms;  
         R 5  is hydrogen; halo; hydroxy; mercapto; (C 1 -C 6 )alkyl; (C 1 -C 6 )alkoxy optionally substituted with one to three halogen atoms; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; cyano; formyl; (C 1 -C 6 )alkylcarbonyl; (C 1 -C 6 )alkyl-C(═O)—O—; HO—(O═C)—; (C 1 -C 6 )alkoxy-C(═O)—; aminocarbonyl; N—(C 1 -C 6 )alkylaminocarbonyl; N,N—[(C 1 -C 6 )alkyl] 2 aminocarbonyl; nitro; amino; (C 1 -C 6 )alkylamino; [(C 1 -C 6 )alkyl] 2 amino; or (C 1 -C 6 )alkyl-S—;  
         wherein said R 5  (C 1 -C 6 )alkyl group may optionally be substituted with one to three substitutents independently selected from halo, hydroxy, (C 1 -C 6 )alkoxy, cyano, nitro, amino, (C 1 -C 6 )alkylamino, (C 1 -C 6 )dialkylamino, HO—(O═C)—, (C 1 -C 6 )alkoxy-(C═O)—, aminocarbonyl, N—(C 1 -C 6 )alkylaminocarbonyl, N,N—[(C 1 -C 6 )alkyl] 2 aminocarbonyl, N—(C 6 -C 10 )arylaminocarbonyl, N,N—[( C 6 -C 10 )aryl] 2 aminocarbonyl, N—(C 1 -C 6 )alkyl-N—(C 6 -C 10 )arylaminocarbonyl, (C 6 -C 10 )aryl, (C 6 -C 10 )aryloxy, (C 2 -C 9 )heteroaryl, (C 2 -C 9 )heteroaryloxy, morpholino-carbonyl, (C 1 -C 6 )alkoxyaminocarbonyl or (C 1 -C 6 )alkyl-carbonylamino;  
         R 6  is selected from the group consisting of: 
 (a) phenyl optionally substituted by 1-3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O)—, (C 1 -C 6 )alkyl-NH—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl- (C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl;  
 (b) phenyl fused to a saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring; wherein either of said phenyl or said fused saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring is optionally substituted by 1 to 2 substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O)—, (C 1 -C 6 )alkyl-NH—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl;  
 (c) phenyl fused to a saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclic containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—; wherein either of said phenyl or said fused saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclic is optionally substituted with one to two substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O)—, (C 1 -C 6 )alkyl-NH—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl;  
 (d) (5- to 7-membered)-carbocyclic optionally containing one or two double bonds; wherein said (5- to 7-membered)-carbocyclic may also be optionally substituted by 1-3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O)—, (C 1 -C 6 )alkyl-NH—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl;  
 (e) (5- to 7-membered)-carbocyclic fused to a saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring; wherein said (5- to 7-membered)-carbocyclic may optionally contain one or two double bonds; wherein either of said (5- to 7-membered)-carbocyclic or said fused saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring is optionally substituted by 1 to 2 substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O)—, (C 1 -C 6 )alkyl-NH—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl;  
 (f) (5- to 7-membered)-carbocyclic fused to a saturated, partially unsaturated or aromatic (5- to 6-membered)-heterocyclic containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—; wherein said (5- to 7-membered)-carbocyclic may optionally contain one or two double bonds; wherein either of said (5- to 7-membered)-carbocyclic or said fused saturated, partially unsaturated or aromatic (5- to 6-membered)-heterocyclic is optionally substituted with one to two substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O)—, (C 1 -C 6 )alkyl-NH—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl;  
 (g) saturated, partially unsaturated or aromatic (5- to 6-membered)heterocyclic containing 1 to 4 ring heteroatoms independently selected from —N═, —NR—, —O—, or —S—, wherein said (5- to 6-membered)heterocyclic is optionally substituted by 1-3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O)—, (C 1 -C 6 )alkyl-NH—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3- substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl;  
 (h) saturated, partially unsaturated or aromatic (5- to 6-membered)heterocyclic containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—; wherein said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclic is fused to a saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring; wherein either of said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclic ring or said fused saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring is optionally substituted by 1 to 2 substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O)—, (C 1 -C 6 )alkyl-NH—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (Cl-C 6 )alkyl; and  
 (i) saturated, partially unsaturated or aromatic (5- to 6-membered)heterocyclic containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S—, or —O—; wherein said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclic is fused to a saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclic containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—; wherein either of said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclic or said fused saturated, partially unsaturated or aromatic (5- to 6-membered)-heterocyclic is optionally substituted with one to two substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O)—, (C 1 -C 6 )alkyl-NH—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-S(═O)—, (C 1 -C 6 )alkyl-SO 2 —, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl;  
 
         R 7  is hydrogen or (C 1 -C 6 )alkyl;  
         R 8  is hydrogen; halo; hydroxy; mercapto; (C 1 -C 6 )alkyl; (C 1 -C 6 )alkoxy optionally substituted with one to three halogen atoms; (C 2 -C 6 )alkenyl; (C 2 -C 6 )alkynyl; cyano; formyl; (C 1 -C 6 )alkylcarbonyl; (C 1 -C 6 )alkyl-C(═O)—O—; HO—(O═C)—; (C 1 -C 6 )alkoxy-C(═O)—; aminocarbonyl; N—(C 1 -C 6 )alkylaminocarbonyl; N,N—[(C 1 -C 6 )alkyl] 2 aminocarbonyl; nitro; amino; (C 1 -C 6 )alkylamino; di[(C 1 -C 6 )alkyl]amino; or (C 1 -C 6 )alkyl-S—;  
         wherein said R 8  (C 1 -C 6 )alkyl group may optionally be substituted with one to three substitutents independently selected from halo, hydroxy, (C 1 -C 6 )alkoxy, cyano, nitro, HO—(O═C)—, (C 1 -C 6 )alkoxy-C(═O)—, aminocarbonyl, N—(C 1 -C 6 )alkylaminocarbonyl, N,N—[(C 1 -C 6 )alkyl] 2 aminocarbonyl, N—(C 6 -C 10 )arylaminocarbonyl, N,N—[(C 6 -C 10 )aryl] 2 aminocarbonyl, N—(C 1 -C 6 )alkyl-N—(C 6 -C 10 )arylaminocarbonyl, (C 6 -C 10 )aryl, (C 6 -C 10 )aryloxy, (C 2 -C 9 )heteroaryl, (C 2 -C 9 )heteroaryloxy, morpholino-carbonyl, (C 1 -C 6 )alkoxyaminocarbonyl or (C 1 -C 6 )alkyl-carbonylamino;  
         and a pharmaceutically acceptable salt thereof.  
       
     
     
         2 . A compound according to  claim 1  wherein said compound has the formula  
       
         
           
           
               
               
           
         
       
       wherein X is CR 8  or N and m is 2.  
     
     
         3 . A compound according to  claim 1  wherein said compound has the formula  
       
         
           
           
               
               
           
         
       
       wherein X is CR 8  or N and m is 2.  
     
     
         4 . A compound according to  claim 1  wherein said compound has the formula  
       
         
           
           
               
               
           
         
       
       wherein m is 2.  
     
     
         5 . A compound according to  claim 1  wherein said compound has the formula  
       
         
           
           
               
               
           
         
       
       wherein m is 2.  
     
     
         6 . A compound according to  claim 1  wherein said compound has the formula  
       
         
           
           
               
               
           
         
       
       wherein m is 2.  
     
     
         7 . A compound according to  claim 1  wherein said compound has the formula  
       
         
           
           
               
               
           
         
       
       wherein m is 2.  
     
     
         8 . A compound according to  claim 1  wherein said compound has the formula  
       
         
           
           
               
               
           
         
       
       wherein m is 2.  
     
     
         9 . A compound according to  claim 1 , wherein said compounds have the formula  
       
         
           
           
               
               
           
         
       
       wherein m is 2.  
     
     
         10 . A compound according to  claim 1 , wherein said compounds have the formula  
       
         
           
           
               
               
           
         
       
       wherein m is 2.  
     
     
         11 . A compound according to  claim 1 , wherein said compounds have the formula  
       
         
           
           
               
               
           
         
       
       wherein m is 2.  
     
     
         12 . A compound according to  claim 1  wherein R 6  is phenyl optionally substituted by 1-3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-(S═O)—, (C 1 -C 6 )alkyl-SO 2 —, (C 1 -C 6 )alkylsulfonylamino, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O), (C 1 -C 6 )alkyl-HN—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—: wherein R′ is hydrogen or (C 1 -C 6 )alkyl.  
     
     
         13 . A compound according to  claim 1  wherein R 6  is phenyl fused to a saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring; wherein either of said phenyl or said fused saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring is optionally substituted by 1 to 2 substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-(S═O)—, (C 1 -C 6 )alkyl-SO 2 —, (C 1 -C 6 )alkylsulfonylamino, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O), (C 1 -C 6 )alkyl-HN—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl.  
     
     
         14 . A compound according to  claim 1  wherein R 6  is phenyl fused to a saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclic ring containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—; wherein either of said phenyl or said fused saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclic ring is optionally substituted with one to two substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-(S═O)—, (C 1 -C 6 )alkyl-SO 2 —, (C 1 -C 6 )alkylsulfonylamino, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O), (C 1 -C 6 )alkyl-HN—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—; (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl.  
     
     
         15 . A compound according to  claim 1  wherein R 6  is (5- to 7-membered)-carbocyclic optionally containing one or two double bonds; wherein said (5- to 7-membered)-carbocyclic may also bed optionally substituted by 1-3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-(S═O)—, (C 1 -C 6 )alkyl-SO 2 —, (C 1 -C 6 )alkylsulfonylamino, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O), (C 1 -C 6 )alkyl-HN—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl.  
     
     
         16 . A compound according to  claim 1  wherein R 6  is (5- to 7-membered)-carbocyclic fused to a saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring; wherein said (5- to 7-membered)-carbocyclic may optionally contain one or two double bonds; wherein either of said (5- to 7-membered)-carbocyclic or said fused saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring is optionally substituted by 1 to 2 substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-(S═O)—, (C 1 -C 6 )alkyl-SO 2 —, (C 1 -C 6 )alkylsulfonylamino, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O), (C 1 -C 6 )alkyl-HN—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl.  
     
     
         17 . A compound according to  claim 1  wherein R 6  is (5- to 6-membered)-carbocyclic fused to a saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclic containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—; wherein said (5- to 7-membered)-carbocyclic may optionally contain one or two double bonds; wherein either of said (5- to 7-membered)-carbocyclic or said fused saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclic is optionally substituted with one to two substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-(S═O)—, (C 1 -C 6 )alkyl-SO 2 —, (C 1 -C 6 )alkylsulfonylamino, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O), (C 1 -C 6 )alkyl-HN—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl.  
     
     
         18 . A compound according to  claim 1  wherein R 6  is saturated, partially saturated or aromatic (5- to 6-membered)heterocyclic containing 1 to 4 ring heteroatoms independently selected from —N═, —NR—, —O—, or —S—, wherein said (5- to 6-membered)heterocyclic is optionally substituted by 1-3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-(S═O)—, (C 1 -C 6 )alkyl-SO 2 —, (C 1 -C 6 )alkylsulfonylamino, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O), (C 1 -C 6 )alkyl-HN—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl.  
     
     
         19 . A compound according to  claim 1  wherein R 6  is saturated, partially saturated or aromatic (5- to 6-membered)heterocyclic containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—; wherein said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclic is fused to a saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring; wherein either of said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclic ring or said fused saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring is optionally substituted by 1 to 2 substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, —OCF 3 , (C 1 -C 6 )alkyl-S—, (C 1 -C 6 )alkyl-(S═O)—, (C 1 -C 6 )alkyl-SO 2 —, (C 1 -C 6 )alkylsulfonylamino, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, H 2 N—(C═O), (C 1 -C 6 )alkyl-HN—(C═O)—, di[(C 1 -C 6 )alkyl]-N—(C═O)—, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)—, (C 1 -C 6 )alkoxy-(C═O)—, (C 6 -C 10 )aryl and (C 2 -C 9 )heterocyclic; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl.  
     
     
         20 . A compound according to  claim 1  wherein R 6  is saturated, partially saturated or aromatic (5- to 6-membered)heterocyclic containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S—, or —O—; wherein said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclic is fused to a saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclic containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—; wherein either of said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclic or said fused saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclic is optionally substituted with one to two substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 2 -C 6 )alkynyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl; wherein each of said (C 1 -C 6 )alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, HO—(C═O)—, nitro, (C 1 -C 6 )alkyl, (C 2 -C 6 )alkenyl, (C 1 -C 6 )alkoxy, (C 1 -C 6 )alkyl-S—, amino, (C 1 -C 6 )alkylamino, di[(C 1 -C 6 )alkyl]amino, amido, (C 1 -C 6 )alkylamido, di[(C 1 -C 6 )alkyl]amido, (C 1 -C 6 )alkyl-(C═O)—O—, (C 1 -C 6 )alkyl-(C═O)—N(R′)—, formyl, (C 1 -C 6 )alkyl-(C═O)— and (C 1 -C 6 )alkoxy-(C═O)—; wherein R′ is hydrogen or (C 1 -C 6 )alkyl.  
     
     
         21 . A compound according to  claim 1  wherein R 2  is hydrogen, halo or (C 1 -C 6 )alkyl.  
     
     
         22 . A compound according to  claim 1  wherein R 2  is methyl or hydrogen.  
     
     
         23 . A compound according to  claim 1  wherein R 3  is cyano or (C 1 -C 6 )alkyl optionally substituted with one to three halo atoms.  
     
     
         24 . A compound according to  claim 1  wherein R 3 is —CF 3  or —CF 2 H.  
     
     
         25 . A compound according to  claim 1  wherein said compound is selected from the group consisting of: 
 2-[5-(4-Bromo-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 {4-[2-(6-Methanesulfonyl-pyridin-3-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-phenyl}-dimethyl-amine;  
 {4-[2-(5-Methanesulfonyl-pyridin-2-yl)-5-trifluoromethyl-2H-pyrazol-3-yl]-phenyl}-dimethyl-amine;  
 2-[3-Difluoromethyl-5-(3-fluoro-4-methoxy-phenyl)-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-[5-(3-Bromo-4-methoxy-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-[5-(3-Chloro-4-methoxy-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-(3-Difluoromethyl-5-p-tolyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine;  
 5-Methanesulfonyl-2-(5-o-tolyl-3-trifluoromethyl-pyrazol-1-yl)-pyridine;  
 5-Methanesulfonyl-2-(5-phenyl-3-trifluoromethyl-pyrazol-1-yl)-pyridine;  
 2-[5-(3-Chloro-4-methoxy-phenyl)-3-difluoromethyl-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-[5-(3-Fluoro-4-methoxy-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 5-Methanesulfonyl-2-[5-(4-methoxy-3-methyl-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-pyridine;  
 2-[3-Difluoromethyl-5-(4-methoxy-3-methyl-phenyl)-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-[5-(2,3-Dihydro-benzo[1,4]dioxin-6-yl)-3-trifluoromethyl-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-(5-Benzo[1,3]dioxol-5-yl-3-trifluoromethyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine;  
 2-[5-(2-Fluoro-4-methoxy-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-[3-Difluoromethyl-5-(2-fluoro-4-methoxy-phenyl)-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-[3-Difluoromethyl-5-(3,4-dimethyl-phenyl)-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-[5-(4-Chloro-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-[5-(4-Fluoro-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-[5-(4-Chloro-3-methyl-phenyl)-3-trifluoromethyl-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-(3-Difluoromethyl-5-phenyl-pyrazol-1-yl)-5-methanesulfonylpyridine;  
 2-[3-Difluoromethyl-5-(4-fluoro-phenyl)-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 5-Methanesulfonyl-2-[5-(6-methyl-naphthalen-2-yl)-3-trifluoromethyl-pyrazol-1-yl]-pyridine;  
 2-(5-Cyclohexyl-3-difluoromethyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine;  
 2-[3-Difluoromethyl-5-(2-fluoro-phenyl)-pyrazol-1-yl]-5-methanesulfonyl-pyridine;  
 2-(4-Chloro-5-phenyl-3-trifluoromethyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine; and  
 2-(5-Cyclohexyl-3-trifluoromethyl-pyrazol-1-yl)-5-methanesulfonyl-pyridine.  
 
     
     
         26 . A pharmaceutical composition for the treatment of a condition selected from the group consisting of arthritis, fever, common cold, dysmenorrhea, menstrual cramps, inflammatory bowel disease, Crohn's disease, emphysema, acute respiratory distress syndrome, asthma, bronchitis, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant toxicity, cachexia, allergic reactions, allergic contact hypersensitivity, cancer, tissue ulceration, peptic ulcers, gastritis, regional enteritis, ulcerative colitis, diverticulitis, recurrent gastrointestinal lesion, gastrointestinal bleeding, coagulation, anemia, synovitis, gout, ankylosing spondylitis, restenosis, periodontal disease, epidermolysis bullosa, osteoporosis, loosening of artificial joint implants, atherosclerosis, aortic aneurysm, periarteritis nodosa, congestive heart failure, myocardial infarction, stroke, cerebral ischemia, head trauma, spinal cord injury, neuralgia, neuro-degenerative disorders, autoimmune disorders, Huntington's disease, Parkinson's disease, migraine, depression, peripheral neuropathy, pain, gingivitis, cerebral amyloid angiopathy, nootropic or cognition enhancement, amyotrophic lateral sclerosis, multiple sclerosis, ocular angiogenesis, corneal injury, macular degeneration, conjunctivitis, abnormal wound healing, muscle or joint sprains or strains, tendonitis, skin disorders, myasthenia gravis, polymyositis, myositis, bursitis, burns, diabetes, tumor invasion, tumor growth, tumor metastasis, corneal scarring, scleritis, immunodeficiency diseases, sepsis, premature labor, hypoprothrombinemia, hemophilia, thyroiditis, sarcoidosis, Behcet's syndrome, hypersensitivity, kidney disease, Rickettsial infections, Protozoan diseases, reproductive disorders and septic shock in a mammal, comprising an amount of a compound of  claim 1  or a pharmaceutically acceptable salt thereof effective in such treatments and a pharmaceutically acceptable carrier.  
     
     
         27 . A pharmaceutical composition for the treatment of a disorder or condition that can be treated or prevented by selectively inhibiting COX-2 in a mammal, comprising a COX-2 selective inhibiting effective amount of a compound according to  claim 1  or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier.  
     
     
         28 . A method for treating a condition selected from the group consisting of arthritis, fever, common cold, dysmenorrhea, menstrual cramps, inflammatory bowel disease, Crohn's disease, emphysema, acute respiratory distress syndrome, asthma, bronchitis, chronic obstructive pulmonary disease, Alzheimer's disease, organ transplant toxicity, cachexia, allergic reactions, allergic contact hypersensitivity, cancer, tissue ulceration, peptic ulcers, gastritis, regional enteritis, ulcerative colitis, diverticulitis, recurrent gastrointestinal lesion, gastrointestinal bleeding, coagulation, anemia, synovitis, gout, ankylosing spondylitis, restenosis, periodontal disease, epidermolysis bullosa, osteoporosis, loosening of artificial joint implants, atherosclerosis, aortic aneurysm, periarteritis nodosa, congestive heart failure, myocardial infarction, stroke, cerebral ischemia, head trauma, spinal cord injury, neuralgia, neuro- degenerative disorders, autoimmune disorders, Huntington's disease, Parkinson's disease, migraine, depression, peripheral neuropathy, pain, gingivitis, cerebral amyloid angiopathy, nootropic or cognition enhancement, amyotrophic lateral sclerosis, multiple sclerosis, ocular angiogenesis, corneal injury, macular degeneration, conjunctivitis, abnormal wound healing, muscle or joint sprains or strains, tendonitis, skin disorders, myasthenia gravis, polymyositis, myositis, bursitis, burns, diabetes, tumor invasion, tumor growth, tumor metastasis, corneal scarring, scleritis, immunodeficiency diseases, sepsis, premature labor, hypoprothrombinemia, hemophilia, thyroiditis, sarcoidosis, Behcet's syndrome, hypersensitivity, kidney disease, Rickettsial infections, Protozoan diseases, reproductive disorders, and septic shock in a mammal, comprising administering to said mammal an amount of a compound according to  claim 1  or a pharmaceutically acceptable salt thereof effective in treating such a condition.  
     
     
         29 . A method for treating a disorder or condition that can be treated or prevented by selectively inhibiting COX-2 in a mammal, comprising administering to a mammal requiring such treatment a COX-2 selective inhibiting effective amount of a compound according to  claim 1  or a pharmaceutically acceptable salt thereof.