4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds as TAK1 inhibitors in disease treatment

摘要

4-alkoxy/aralkoxy-5-substituted-pyrrolopyrimidine compounds, pharmaceutically acceptable salts, solvates and pharmaceutical compositions of compounds embraced by Formula (I), provide a therapeutic benefit to subjects with disease conditions, especially cancer, wherein R1 and R2 are as defined in the detailed description.;

主权项

1. A compound, or a pharmaceutically acceptable salt, or solvate of a compound or salt, of Formula (I): wherein: R1 is selected from the group consisting of alkyl, cycloalkyl, aryl, aralkyl, fully or partially saturated heterocyclylalkyl, heteroaryl and heteroaralkyl, wherein alkyl, cycloalkyl, aryl, aralkyl, fully or partially saturated heterocyclylalkyl, heteroaryl and heteroaralkyl are optionally substituted, on any substitutable carbon, with one or more R3 radicals; R2 is selected from the group consisting of alkenyl, alkynyl,  cycloalkenyl, heterocycloalkenyl and heteroaryl, wherein each alkenyl moiety is optionally substituted on any substitutable carbon with one or more R7 or R17 radicals, wherein alkynyl is optionally substituted on any substitutable carbon with one or more R117 radicals, wherein cycloalkenyl is optionally substituted on any substitutable carbon with one or more R9 radicals, wherein heterocycloalkenyl is optionally substituted on any substitutable carbon with one or more R119 radicals, and wherein heteroaryl is optionally substituted on any substitutable carbon with one or more R19 radicals; R3 is selected from the group consisting of alkyl, hydroxy, alkoxy, aryloxy, oxo, acyl, carboxy, hydroxyalkyl, halo, haloalkyl, cyano, amino, monoalkylamino, dialkylamino, acylamino, aminoalkyl, monoalkylaminoalkylene, dialkylaminoalkylene, cycloalkyl, alkylsulfonyl, alkylsulfonylamino, aminosulfonyl, aminocarbonyl, cyanoalkylcarbonyl, alkoxycarbonyl, alkoxycarbonyloxy, alkoxycarbonylamino, alkoxycarbonylaminoalkylene, alkylureido, alkylureidoalkylene, dialkylaminosulfonyl and monoalkylaminosulfonyl; R4 is selected from the group consisting of cyano, haloacyl, alkenylcarbonyl, hydroxyalkenylcarbonyl, aminoalkenylcarbonyl, monoalkylaminoalkenylcarbonyl, dialkylaminoalkenylcarbonyl, haloalkenylcarbonyl, cyanoalkenylcarbonyl, alkoxycarbonylalkenylcarbonyl, alkynylcarbonyl, hydroxyalkynylcarbonyl, alkylcarbonylalkenylcarbonyl, arylcarbonylalkenylcarbonyl, cycloalkylcarbonylalkenylcarbonyl, aminocarbonylalkenylcarbonyl, monoalkylaminocarbonylalkenylcarbonyl, dialkylaminocarbonylalkenylcarbonyl and alkenylsulfonyl; R14 is selected from the group consisting of H, alkyl, cycloalkyl and aryl; R5 is selected from the group consisting of H, alkyl and cycloalkyl; R15 is selected from the group consisting of H, alkyl and cycloalkyl; R6 is selected from the group consisting of alkyl, haloalkyl, alkenyl, hydroxyalkenyl, cyanoalkenyl, haloalkenyl, aminoalkenyl, monoalkylaminoalkenyl, dialkylaminoalkenyl, cyanoalkylamino, aminocarbonylalkenyl, monoalkylaminocarbonylalkenyl, dialkylaminocarbonylalkenyl, alkoxycarbonylalkenyl, alkylcarbonylalkenyl, arylcarbonylalkenyl, heteroarylcarbonylalkenyl, cycloalkylcarbonylalkenyl and cyanocycloalkylamino; each of R7, R17 and R117 is independently selected from the group consisting of alkyl, acyl, cyano, halo, aminocarbonyl, monoalkylaminocarbonyl, dialkylaminocarbonyl, mono(hydroxyalkyl)aminocarbonyl, aroyl and heterocyclocarbonyl; R8 is selected from the group consisting of alkenyl, hydroxyalkenyl and cycloalkenyl; each of R9 and R119 is independently selected from the group consisting of alkyl, oxo, cyano and halo; and R19 is selected from the group consisting of alkyl, cyano and halo.