Sulfonyl aryl triazoles as anti-inflammatory/analgesic agents

A compound of the formula

• 14
• wherein
• m is 0, 1, or 2;
• R1 is selected from the group consisting of:
• (a) (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C1-C6)alkylcarbonyl, formyl, formamidyl, (C1-C6)alkylcarbonyl, cyano, mercapto, nitro, hydroxycarbonyl, (C1-C6)alkoxycarbonyl, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, (C1-C6)alkoxyamido, (C1-C6)alkylthio, (C3-C7)carbocyclylthio, (C6-C10)arylthio, (C2-C9)heteroarylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, (C6-C10)aryloxy, (C2-C9)heteroaryloxy, (C2-C9)heterocyclylcarbonyl, or (C1-C6)alkylcarbonyl-N(R2)—;
• (b) phenyl optionally substituted by one to three substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, hydroxycarbonyl, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, —OCF3, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, N—(C1-C6)alkoxyamido, (C1-C6)alkylcarbonyloxy, (C1-C6)alkylcarbonyl-N(R2)—, formyl, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C6-C10)aryl and (C2-C9)heterocyclyl;
• (c) phenyl fused to a saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclyl ring;
• wherein either of said phenyl or said fused saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclyl ring is optionally substituted by one to two substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, hydroxycarbonyl, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, —OCF3, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, N—(C1-C6)alkoxyamido, (C1-C6)alkylcarbonyloxy, (C1-C6)alkylcarbonyl-N(R2)—, formyl, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C6-C10)aryl and (C2-C9)heterocyclyl;
• (d) phenyl fused to a saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclyl containing one to two ring heteroatoms independently selected from the group consisting of —N═, —NR2—, —S— and —O—;
• wherein either of said phenyl or said fused saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclyl 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, hydroxycarbonyl, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, —OCF3, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, N—(C1-C6)alkoxyamido, (C1-C6)alkylcarbonyloxy, (C1-C6)alkylcarbonyl-N(R2)—, formyl, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C6-C10)aryl and (C2-C9)heterocyclyl;
• (e) (3- to 7-membered)-carbocyclyl optionally containing one or two double bonds;
• wherein said (3- to 7-membered)-carbocyclyl may also be optionally substituted by one to three substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, hydroxycarbonyl, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, —OCF3, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, N—(C1-C6)alkoxyamido, (C1-C6)alkylcarbonyloxy, (C1-C6)alkylcarbonyl-N(R2)—, formyl, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C6-C10)aryl and (C2-C9)heterocyclyl;
• (f) (5- to 7-membered)-carbocyclyl fused to a saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclyl ring;
• wherein said (5- to 7-membered)-carbocyclyl may optionally contain one or two double bonds;
• wherein either of said (5- to 7-membered)-carbocyclyl or said fused saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclyl ring is optionally substituted by one to two substituents per ring, wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, hydroxycarbonyl, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, —OCF3, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, N—(C1-C6)alkoxyamido, (C1-C6)alkylcarbonyloxy, (C1-C6)alkylcarbonyl-N(R2)—, formyl, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C6-C10)aryl and (C2-C9)heterocyclyl;
• (g) (5- to 7-membered)-carbocyclyl fused to a saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclyl containing one to two ring heteroatoms independently selected from the group consisting of —N═, —NR2—, —S— and —O—;
• wherein said (5- to 7-membered)-carbocyclyl may optionally contain one or two double bonds;
• wherein either of said (5- to 7-membered)-carbocyclyl or said fused saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclyl 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, hydroxycarbonyl, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, —OCF3, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, N—(C1-C6)alkoxyamido, (C1-C6)alkylcarbonyloxy, (C1-C6)alkylcarbonyl-N(R2)—, formyl, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C6-C10)aryl and (C2-C9)heterocyclyl;
• (h) saturated, partially saturated or aromatic (5- to 6-membered) heterocyclyl containing one to four ring heteroatoms independently selected from the groups consisting of —N═, —NR2—, —O—, and —S—;
• wherein said (5- to 6-membered) heterocyclyl is optionally substituted by one to three substituents independently selected from the group consisting of halo, hydroxy, cyano, mercapto, hydroxycarbonyl, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, —OCF3, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, N—(C1-C6)alkoxyamido, (C1-C6)alkylcarbonyloxy, (C1-C6)alkylcarbonyl-N(R2)—, formyl, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C6-C10)aryl and (C2-C9)heterocyclyl;
• (i) saturated, partially saturated or aromatic (5- to 6-membered) heterocyclyl containing one to two ring heteroatoms independently selected from the group consisting of —N═, —NR2—, —S— and —O—;
• wherein said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclyl is fused to a saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclyl ring;
• wherein either of said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclyl ring or said fused saturated, partially saturated or aromatic (5- to 7-membered)-carbocyclyl ring is optionally substituted by one to two substituents per ring;
• wherein said substituents are independently selected from the group consisting of halo, hydroxy, cyano, mercapto, hydroxycarbonyl, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, —OCF3, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, N—(C1-C6)alkoxyamido, (C1-C6)alkylcarbonyloxy, (C1-C6)alkylcarbonyl-N(R2)—, formyl, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C6-C10)aryl and (C2-C9)heterocyclyl;
• and
• (j) saturated, partially saturated or aromatic (5- to 6-membered)heterocyclyl containing one to two ring heteroatoms independently selected from the group consisting of —N═, —NR2—, —S—, and —O—;
• wherein said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclyl is fused to a saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclyl containing one to two ring heteroatoms independently selected from the group consisting of —N═, —NR2—, —S— and —O—;
• wherein either of said saturated, partially saturated or aromatic (5- to 6-membered)heterocyclyl or said fused saturated, partially saturated or aromatic (5- to 6-membered)-heterocyclyl 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, hydroxycarbonyl, nitro, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, —OCF3, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, N—(C1-C6)alkoxyamido, (C1-C6)alkylcarbonyloxy, (C1-C6)alkylcarbonyl-N(R2)—, formyl, (C1-C6)alkylcarbonyl, (C1-C6)alkoxycarbonyl, (C6-C10)aryl and (C2-C9)heterocyclyl;
• wherein each of said R1 (a), (b), (c), (d), (e), (f), (g), (h), (i), or (j) (C1-C6)alkyl group wherever they occur may optionally be substituted with one to three substituents independently selected from the group consisting of halo, hydroxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, carbonyl, formyl, formamidyl, (C1-C6)alkylcarbonyl, cyano, mercapto, nitro, hydroxycarbonyl, (C1-C6)alkoxycarbonyl, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, (C1-C6)alkoxyamido, (C6-C10)aryl, (C6-C10)aryloxy, (C2-C9)heteroaryl, (C2-C9)heteroaryloxy, (C2-C9)heteroarylcarbonyl, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, (C1-C6)alkylcarbonyl-N(R2)—, and (C1-C6)alkylcarbonyloxy;
• R2 is hydrogen or (C1-C6)alkyl;
• R3 is hydrogen, halo, (C1-C6)alkyl, (C2-C6)alkenyl, (C2-C6)alkynyl, (C1-C6)alkoxy, (C3-C7)carbocyclyl, (C1-C6)alkylcarbonyl-, formyl, formamidyl, cyano, nitro, hydroxycarbonyl, (C1-C6)alkoxycarbonyl, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, amino-SO2—, N—(C1-C6)alkylamino-SO2—, N,N—[(C1-C6)alkyl]2amino-SO2—, (C6-C10)arylamino-SO2—, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, (C6-C10)aryl, (C6-C10)aryloxy, (C2-C9)heteroaryl, (C2-C9)heteroaryloxy, (C2-C9)heteroarylcarbonyl, (C1-C6)alkoxyamido, (C1-C6)alkylthio, (C6-C10)arylthio, (C2-C9)heteroarylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, (C1-C6)alkyl-SO2-amino, or (C1-C6)alkylcarbonyl-N(R2)—;
• wherein each of said R3 (C1-C6)alkyl group wherever they occur may optionally be substituted with one to three substituents independently selected from the group consisting of halo, hydroxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, carbonyl, formyl, formamidyl, (C1-C6)alkylcarbonyl, cyano, mercapto, nitro, hydroxycarbonyl, (C1-C6)alkoxycarbonyl, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, (C1-C6)alkoxyamido, (C6-C10)aryl, (C6-C10)aryloxy, (C2-C9)heteroaryl, (C2-C9)heteroaryloxy, (C2-C9)heteroarylcarbonyl, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, (C1-C6)alkylcarbonyl-N(R2)—, and (C1-C6)alkylcarbonyloxy;
• R4 is (C3-C7)carbocyclyl, (C6-C10)aryl, (C2-C9)heteroaryl, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, formyl-N(R2)—, (C1-C6)alkylcarbonyl-N(R2)—, (C1-C6)alkyloxycarbonyl-N(R2)—, or (C1-C6)alkyl-SO2-amino;
• wherein each of said R4 (C1-C6)alkyl group wherever they occur may optionally be substituted with one to three substituents independently selected from the group consisting of halo, hydroxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, carbonyl, formyl, formamidyl, (C1-C6)alkylcarbonyl, cyano, mercapto, nitro, hydroxycarbonyl, (C1-C6)alkoxycarbonyl, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, (C1-C6)alkoxyamido, (C6-C10)aryl, (C6-C10)aryloxy, (C2-C9)heteroaryl, (C2-C9)heteroaryloxy, (C2-C9)heteroarylcarbonyl, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, (C1-C6)alkylcarbonyl-N(R2)—, and (C1-C6)alkylcarbonyloxy;
• R5 is hydrogen, halo, hydroxy, mercapto, (C1-C6)alkyl, (C1-C6)alkoxy optionally substituted with one to three halogen atoms, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, cyano, formyl, (C1-C6)alkylcarbonyl, (C1-C6)alkylcarbonyloxy, hydroxycarbonyl, (C1-C6)alkoxycarbonyl, amino, N—(C1-C6)alkylamino, N,N—[(C1-C6)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, nitro, or (C1-C6)alkylthio;
• wherein each of said R5 (C1-C6)alkyl group wherever they occur may optionally be substituted with one to three substituents independently selected from the group consisting of halo, hydroxy, (C2-C6)alkenyl, (C2-C6)alkynyl, (C3-C7)carbocyclyl, (C1-C6)alkoxy, carbonyl, formyl, formamidyl, (C1-C6)alkylcarbonyl, cyano, mercapto, nitro, hydroxycarbonyl, (C1-C6)alkoxycarbonyl, amino, N—(C1-C6)alkylamino, N,N—[(C1-C8)alkyl]2amino, N—(C3-C7)carbocyclylamino, N—(C6-C10)arylamino, N—(C1-C6)alkyl-N—(C6-C10)arylamino, N—(C2-C9)heteroarylamino, amido, N—(C1-C6)alkylamido, N,N—[(C1-C6)alkyl]2amido, N—(C6-C10)arylamido, N—(C1-C6)alkyl-N—(C6-C10)arylamido, (C1-C6)alkoxyamido, (C6-C10)aryl, (C6-C10)aryloxy, (C2-C9)heteroaryl, (C2-C9)heteroaryloxy, (C2-C9)heteroarylcarbonyl, (C1-C6)alkylthio, (C1-C6)alkyl-S(═O)—, (C1-C6)alkyl-SO2—, (C1-C6)alkylcarbonyl-N(R2)—, and (C1-C6)alkylcarbonyloxy;
• and a pharmaceutically acceptable salt thereof.