2,3-DIHYDROBENZOFURAN-5YL COMPOUNDS AS DYRK KINASE INHIBITORS

摘要

The present invention relates to compounds of below Formula (I), physiologically functional derivatives or salts thereof, where the groups R1, R2, R3, R4, RA, X1, and A, as well as the variables n, m and p are detailed further herein.;;In another aspect, the present invention provides methods for their preparation, their medical use and pharmaceutical compositions comprising said compounds, physiologically functional derivatives, solvates or salts thereof.

主权项

1. A compound of formula (I) or a physiologically functional derivative, solvate or salt thereof, wherein the X1-azol moiety is attached at the 5- or 6-position of the 2,3-dihydrobenzofuran moiety, n is an integer from 0 to 2; m is an integer from 0 to 3; p is an integer from 0 to 4; R1 is independently selected from the group comprising H, halogen, alkyl, aralkyl, haloalkyl, haloalkoxy, OH, alkoxy, —CN, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, —S—R′, —SO—R′, nitro, —NH2, —N(R′)2, —NH(R′), —NHCO(R′), —CONH2, —CONH(R′), —CO(R′), —COH, —COO(R′), —COOH, —SO2NH2, —SO2NH(R′), —SO2(R′), —NH—SO2(R′) and —NHCOOR′; R2 is independently selected from the group comprising H, halogen, alkyl, aralkyl, haloalkyl, haloalkoxy, OH, alkoxy, —CN, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, —S—R′, —SO—R′, nitro, —NH2, —N(R′)2, —NH(R′), —NHCO(R′), —CONH2, —CONH(R′), —CO(R′), —COH, —COO(R′), —COOH, —SO2NH2, —SO2NH(R′), —SO2(R′), —NH—SO2(R′) and —NHCOOR′; R3 is independently selected from the group comprising H, halogen, alkyl, aralkyl, haloalkyl, haloalkoxy, OH, alkoxy, —CN, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, —S—R′, —SO—R′, nitro, —NH2, —N(R′)2, —NH(R′), —NHCO(R′), —CONH2, —CONH(R′), —CO(R′), —COH, —COO(R′), —COOH, —SO2NH2, —SO2NH(R′), —SO2(R′), —NH—SO2(R′) and —NHCOOR′; R4 is independently selected from the group comprising H, alkyl, aralkyl, haloalkyl, haloalkoxy, OH, alkoxy, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, —CONH2, —CONH(R′), —CO(R′), —COO(R′), and —SO2(R′); X1 is independently selected from the group comprising NRn, O or S; Rn is independently selected from the group comprising H, alkyl, aralkyl, haloalkyl, haloalkoxy, OH, alkoxy, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, —CONH2, —CONH(R′), —CO(R′), —COO(R′), and —SO2(R′); A is a monocyclic or bicyclic heteroaromatic ring system consisting of 5 to 10 ring atoms, at least one of which is an N atom, wherein optionally one to three further ring atoms are heteroatoms independently selected from the group comprising O, S and N and wherein the remaining ring atoms are carbon atoms; RA is independently selected from the group comprising H, halogen, CN, NO2, alkyl, haloalkyl, aryl, heteroaryl, cycloalkyl, heterocycloalkyl, —OR′, —CO—R′, —COO—R′, —CONH—R′, —NHCO—R′, —CON(R′)2, —NR′CO—R′, —NR′—CONR′, —NR′—COOR′, —S—R′, —SO—R′, —SO2—R′, —NHSO2—R′, —SO2NH—R′, —O—CO—NHR′, —O—CO—R′, —R′—O—R′, —R′—CO—R′, —R′—NH—R′, —R′—CONH—R′, —R′—NHCO—R′, —CONH-alkyl-O—R′, —CONH-alkyl-R′, —NHCO-alkyl-O—R′, —NHCO-alkyl-R′, —CO—R′-alkyl-R′, —CO—R′-alkyl, N(R′)2, —NHR′, NH2, —S—R′, —S-alkyl-R′ and alkyl-R′; R′ is independently selected from the group comprising H, alkyl, haloalkyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl; wherein any of the aforementioned alkyl, aryl, heteroaryl, cycloalkyl and heterocycloalkyl may independently be substituted with one or more, particularly one to three, more particularly one or two substituents R″, wherein R″ independently selected from the group comprising C1-4-alkyl halogen, C1-4-haloalkyl, OH, C1-4-alkoxy, C1-4-haloalkoxy, nitro, —NH2, —N(C1-4-alkyl)2, —NH(C1-4-alkyl), —NHCO(C1-4-alkyl), —CONH2, —CONH(C1-4-alkyl), —CO(C1-4-alkyl), —COH, —COO(C1-4-alkyl), —COOH and —CN.