| 主权项 |
1. A method for inhibiting an MEK kinase, said method comprising: administering a composition to an individual in need of said inhibiting; wherein the composition comprises an effective amount of a compound of formula I and optionally one or more pharmaceutically acceptable carriers, diluents, or excipients; and wherein the compound of formula I is represented by the following structure wherein, R1 is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-heterocyclyl; R2 is selected from the group consisting of —R6-E, —SO2R7, and —C(O)R8; R3 is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl; R4 is selected from the group consisting of hydrogen, halogen, substituted- or unsubstituted-alkyl, and substituted- or unsubstituted-cycloalkyl; R5 is substituted- or unsubstituted-aryl, wherein the substituents are selected from with Ra and Rb; Ra and Rb are selected from the group consisting of hydrogen, halogen and haloalkyl; R6 is selected from the group consisting of direct bond, —[C(Rc)Rd]nNR9—, —[C(Rc)Rd]nO—, —NHC(═O)[C(Rc)Rd]p—, —S(O)2NH—, —NHC(═O)[CRc(Rd)]NR9—, —NHC(═O)[CRc(Rd)]O—, and —NHS(O)2—; Rc and Rd are each independently selected from the group consisting of hydrogen and substituted- or unsubstituted-alkyl; E is substituted- or unsubstituted-four membered heterocyclic ring, wherein the substituents are selected from the group consisting of alkyl, halogen, —C(═O)ORe, and —ORe; Re is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, and substituted or unsubstituted cycloalkyl; R7 is selected from the group consisting of substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-cycloalkenyl; R8 is selected from the group consisting of substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, substituted- or unsubstituted-alkynyl, substituted- or unsubstituted-cycloalkyl, and substituted- or unsubstituted-cycloalkenyl; R9 is selected from the group consisting of hydrogen, substituted- or unsubstituted-alkyl, substituted- or unsubstituted-alkenyl, substituted- or unsubstituted-alkynyl, substituted- or unsubstituted-cycloalkyl and substituted or unsubstituted-cycloalkenyl; n is an integer selected from the group consisting of 0, 1 and 2; p is an integer selected from the group consisting of 0 and 1; when the alkyl group and alkenyl group is substituted, the alkyl group and alkenyl group is substituted with 1 to 4 substituents independently selected from the group consisting of oxo, halogen, nitro, cyano, perhaloalkyl, cycloalkyl, aryl, heteroaryl, heterocyclyl, —OR10b, —SO2R10a, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —OR10a, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, —N(H)C(═O)N(alkyl)R10, —NH—SO2-alkyl and —NH—SO2-cycloalkyl; when the cycloalkyl group and cycloalkenyl group is substituted, the cycloalkyl group and cycloalkenyl group is substituted with 1 to 3 substituents independently selected from the group consisting of oxo, halogen, nitro, cyano, alkyl, alkenyl, perhaloalkyl, aryl, heteroaryl, heterocyclyl, —OR10b, —SO2R10a, —C(═O)R10a, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, and —N(H)C(═O)N(alkyl)R10, —NH—SO2-alkyl and —NH—SO2-cycloalkyl; when the aryl group is a substituted, the aryl group is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, nitro, cyano, hydroxy, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, heterocycle, —O-alkyl, —O-perhaloalkyl, —N(alkyl)alkyl, —N(H)alkyl, —NH2, —SO2-alkyl, —SO2-perhaloalkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)alkyl, —C(═O)N(alkyl)alkyl, —C(═O)N(H)alkyl, —C(═O)NH2, —SO2N(alkyl)alkyl, —SO2N(H)alkyl, —SO2NH2, —NH—SO2-alkyl and —NH—SO2-cycloalkyl; when the heteroaryl group is substituted, the heteroaryl group is substituted with 1 to 3 substituents independently selected from the group consisting of halogen, nitro, cyano, hydroxy, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, heterocycle, —O-alkyl, O-perhaloalkyl, —N(alkyl)alkyl, —N(H)alkyl, —NH2, —SO2-alkyl, —SO2-perhaloalkyl, —N(alkyl)C(═O)alkyl, —N(H)C(═O)alkyl, —C(═O)N(alkyl)alkyl, —C(═O)N(H)alkyl, —C(═O)NH2, —SO2N(alkyl)alkyl, —SO2N(H)alkyl, —SO2NH2, —NH—SO2-alkyl and —NH—SO2-cycloalkyl; when the heterocyclyl group is substituted, the heterocyclyl group is substituted with 1 to 3 substituents, when the heterocyclic group is substituted on a ring carbon of the ‘heterocycle’, the substituents are independently selected from the group consisting of halogen, nitro, cyano, oxo, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, heterocyclyl, —OR10b, —C(═O)OR10a, —OC(═O)R10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —N(H)C(═O)R10a, —N(H)R10, —N(alkyl)R10, —N(H)C(═O)N(H)R10, —N(H)C(═O)N(alkyl)R10; when the heterocyclic group is substituted on a ring nitrogen of the ‘heterocycle’, substituents are independently selected from the group consisting of alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, —SO2R10a, —C(═O)R10a, C(═O)OR10a, —C(═O)N(H)R10, —C(═O)N(alkyl)R10, —NH—SO2-alkyl and —NH—SO2-cycloalkyl; R10 is selected from the group consisting of hydrogen, alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl; R10a is selected from the group consisting of alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl; and R10b is selected from the group consisting of hydrogen, alkyl, alkenyl, perhaloalkyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl; wherein the compound of formula I includes a tautomeric form thereof, a stereoisomeric form thereof, or a pharmaceutically acceptable salt thereof. |
