Sulfamoylheteroaryl pyrazole compounds as anti-inflammatory/analgesic agents

A compound of the following formula:

• 24
• or a pharmaceutically acceptable salt thereof, wherein
• A is selected from the group consisting of
• a) (5- to 6-membered)-heteroaryl containing 1 to 4 ring heteroatoms independently selected from —N═, —NR′—, —O—, or —S—, wherein said heteroaryl is optionally substituted with 1-3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amido, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• wherein R′ is hydrogen or (C1-C4)alkyl;
• wherein each of said (C1-C4)alkyl may optionally be substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amido, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• b) (5- to 6-membered)-heteroaryl containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—;
• wherein said heteroaryl is fused to a saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring;
• wherein either of said (5- to 6-membered)-heteroaryl ring or said fused saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring may optionally be substituted with 1 to 2 substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amido, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• wherein R′ is hydrogen or (C1-C4)alkyl;
• wherein each of said (C1-C4)alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amido, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• and
• c) (5- to 6-membered)-heteroaryl containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S—, or —O—;
• wherein said heteroaryl is fused to a (5- to 6-membered)-heteroaryl containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—;
• wherein either of said (5- to 6-membered)-heteroaryl or said fused (5- to 6-membered)-heteroaryl 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, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amido, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• wherein R′ is hydrogen or (C1-C4)alkyl;
• wherein each of said (C1-C4)alkyl may optionally be substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amido, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• R1 is selected from the,group consisting of
• a) (5- to 6-membered)-heteroaryl containing 1 to 4 ring heteroatoms independently selected from —N═, —NR—, —O—, or —S—, wherein said heteroaryl is optionally substituted with 1-3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amido, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• wherein R′ is hydrogen or (C1-C4)alkyl;
• wherein each of said (C1-C4)alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amido, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• b) (5- to 6-membered)-heteroaryl containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—;
• wherein said heteroaryl is fused to a saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring;
• wherein either of said (5- to 6-membered)-heteroaryl ring or said fused saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclic ring is optionally substituted with 1 to 2 substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amido, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• wherein R′ is hydrogen or (C1-C4)alkyl;
• wherein each of said (C1-C4)alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amido, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• and
• c) (5- to 6-membered)-heteroaryl containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S—, or —O—;
• wherein said heteroaryl is fused to a (5- to 6-membered)-heteroaryl containing 1 to 2 ring heteroatoms independently selected from the group consisting of —N═, —NR′—, —S— or —O—;
• wherein either of said (5- to 6-membered)-heteroaryl or said fused (5- to 6-membered)-heteroaryl 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, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amino, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• wherein R′ is hydrogen or (C1-C4)alkyl;
• wherein each of said (C1-C4)alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, carboxy, nitro, (C1-C4)alkyl, (C2-C4)alkenyl, (C2-C4)alkynyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, amino, (C1-C4)alkylamino, di[(C1-C4)alkyl]amino, amido, (C1-C4)alkylamido, di[(C1-C4)alkyl]amido, (C1-C4)alkyl-(C═O)—O—, (C1-C4)alkyl-(C═O)—N(R′)—, formyl, (C1-C4)alkyl-(C═O)— and (C1-C4)alkoxy-(C═O)—;
• R2 is NH2;
• R3 and R4 are independently selected from the group consisting of hydrogen, halo, (C1-C4)alkyl, (C2-C4)alkenyl, (C1-C4)alkoxy, (C1-C4)alkyl-(C═O)—, cyano, nitro, carboxy, (C1-C4)alkoxy-(C═O)—, amino-(C═O)—, (C1-C4)alkyl-amino-(C═O)—, di[(C1-C4)alkyl]-amino-(C═O)—, N-[(C1-C4)alkyl]-N-phenyl-amino-(C═O)—, N-[(C1-C4)alkyl]-N-[(5- to 6-membered)-heteroaryl]-amino-(C═O)—, wherein said (5- to 6-)membered heteroaryl contains 1 to 4 heteroatoms independently selected from —N═, —NR′—, —O— and —S—;
• wherein each of said (C1-C4)alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, hydroxy, cyano, phenyl, (C1-C4)alkoxy and (5- to 6-membered)-heteroaryl containing 1 to 4 heteroatoms independently selected from —N═, —NR′—, —O— and —S—;
• wherein each of said R′ is independently hydrogen or (C1-C4)alkyl;
• and
• X1, X2, X3 and X4 are independently selected from the group consisting of hydrogen, halo, hydroxy, cyano, mercapto, carboxy, nitro, (C1-C4)alkyl, (C1-C4)alkoxy, (C1-C4)alkyl-S—, (C1-C4)alkyl-amino-, di[(C1-C4)alkyl]-amino-, (C1-C4)alkyl-(C═O)—, (C1-C4)alkoxy-(C═O)— and amino-C(═O)—;
• wherein each said (C1-C4)alkyl is optionally substituted with 1 to 3 substituents independently selected from the group consisting of halo, amino, (C1-C4)alkyl-amino-, di[(C1-C4)alkyl]-amino-, hydroxy, carboxy, amino-(C═O)—, (C1-C4)alkyl-amino-C(═O)—, di[(C1-C4)alkyl]-amino-C(═O)—, mercapto, (C1-C4)alkyl-S— and (C1-C4)alkoxy-(C═O)—.