Methods of treating p38 kinase-associated conditions and pyrrolotriazine compounds useful as kinase inhibitors

A compound having the formula (II):

• or a pharmaceutically acceptable salt, prodrug or solvate thereof, wherein:
• R3 is methyl, CF3, or CH3;R5 is hydrogen or alkyl;
• Y is —C(═O)NR23—, —NR23C(═O)NR23—, —SO2NR23, or —NR23SO2—;
• R18 and R23 are selected from hydrogen, alkyl, alkoxy, aryl, and aryl substituted with one to three R19, except when Y is —NR23SO2—, R18 is C1-4alkyl or aryl optionally substituted with one to three R19;
• X is selected from —O—, —OC(═O)—, —S—, —S(═O)—, —SO2—, —C(═O)—, —CO2—, —NR10—, —NR10C(═O)—, —NR10C(═O)NR11—, —NR10CO2—, —NR10SO2—, —NR10SO2NR11—, —SO2NR10—, and —C(═O)NR10—, or X is absent;
• R1 is hydrogen, —CH3, —OH, —OCH3, —SH, —SCH3, —OC(═O)R21, —S(═O)R22, —SO2R22, —SO2NR24R25, —CO2R21, —C(═O)NR24R25, —NH2, —NR24R25, —NR21SO2NR24R25, —NR21SO2R22, —NR24C(═O)R25, —NR24CO2R25, —NR21C(═O)NR24R25, halogen, nitro, or cyano;
• R2 is selected from
• a) hydrogen, provided that R2 is not hydrogen when X is —S(═O)—, —SO2—, —NR10CO2—, or —NR10SO2—;
• b) alkyl, alkenyl, and alkynyl optionally substituted with up to four R26, or pentafluoroalkyl;
• c) aryl and heteroaryl optionally substituted with up to three R27;
• and
• d) heterocyclo and cycloalkyl optionally substituted with keto (═0), up to three R27, and/or having a carbon-carbon bridge of 3 to 4 carbon atoms;
• R6 is hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, substituted heterocyclo, —NR7R8, —OR7, or halogen;
• R10 is hydrogen or alkyl;
• R13 and R19 at each occurrence are independently selected from alkyl, halo, trifluoromethoxy, trifluoromethyl, hydroxy, alkoxy, alkanoyl, alkanoyloxy, thiol, alkylthio, ureido, nitro, cyano, carboxy, carboxyalkyl, carbamyl, alkoxycarbonyl, alkylthiono, arylthiono, arylsulfonylamine, C1-4alkylsulfonylamine, sulfonic acid, alkysulfonyl, sulfonamido, and aryloxy, wherein each R13 and/or R19 group may be further substituted by hydroxy, alkyl, substituted alkyl, alkoxy, aryl, or aralkyl;
• R7, R8, R21, R24, and R25 are independently selected from hydrogen, alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, and substituted heterocyclo;
• R22 is alkyl, substituted alkyl, aryl, substituted aryl, heterocyclo, or substituted heterocyclo;
• R26 is selected from halogen, trifluoromethyl, haloalkoxy, keto (═O), nitro, cyano, —SR28, —OR28, —NR28R29, —NR28SO2, —NR28SO2R29, —SO2R28, —SO2NR28R29, —CO2R28, —C(═O)R28, —C(═O)NR28 R29, —OC(═O)R28, —OC(═O)NR28 R29, —NR28C(═O)R29, —NR28CO2R29, ═N—OH, ═N—O-alkyl;
• aryl optionally substituted with one to three R27;
• cycloalkyl optionally substituted with keto(═O), one to three R27, or having a carbon-carbon bridge of 3 to 4 carbon atoms;
• and heterocyclo optionally substituted with oxo (═O), one to three R27, or having a carbon-carbon bridge of 3 to 4 carbon atoms;
• wherein R28 and R29 are each independently selected from hydrogen, alkyl, alkenyl, aryl, aralkyl, C3-7cycloalkyl, and C3-7heterocycle, or may be taken together to form a C3-7heterocycle;
• and wherein each R28 and R29 in turn is optionally substituted with up to two of alkyl, alkenyl, halogen, haloalkyl, haloalkoxy, cyano, nitro, amino, hydroxy, alkoxy, alkylthio, phenyl, benzyl, phenyloxy, and benzyloxy;
• R27 is selected from alkyl, R32, and C1-4alkyl substituted with one to three R32, wherein each R32 group is independently selected from halogen, haloalkyl, haloalkoxy, nitro, cyano, —SR30, —OR30, —NR30R31, —NR30SO2, —NR30SO2R31, —SO2R30, —SO2NR30R31, —CO2R30, —C(═O)R30, —C(═O)NR30R31, —OC(═O)R30, —OC(═O)NR30R31, —NR30C(═O)R31, —NR30CO2R31, and a 3 to 7 membered carbocyclic or heterocyclic ring optionally substituted with alkyl, halogen, hydroxy, alkoxy, haloalkyl, haloalkoxy, nitro, amino, or cyano, wherein R30 and R31 are each independently selected from hydrogen, alkyl, alkenyl, aryl, aralkyl, C3-7cycloalkyl, and heterocycle, or may be taken together to form a C3-7heterocycle;
• and n is 0, 1 or 2.