<i>O</i>-GlcNAc transferase inhibitors and uses thereof

摘要

The present invention provides inhibitors of O-GIcNAc transferase. Typically, the inhibitors are quinolinone-6-sulfonamides. The invention also provides pharmaceutical compositions thereof and methods for using the same in diabetes and complications thereof, neurodegenerative diseases, cancers, autoimmune diseases, and inflammatory diseases.

主权项

1. A compound of formula (I):or a pharmaceutically acceptable salt thereof, wherein
denotes a single or double bond; R1 is cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; substituted or unsubstituted, branched or unbranched arylalkyl; or substituted or unsubstituted, branched or unbranched heteroarylalkyl; R2 and R3 are independently cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted aryl; substituted or unsubstituted heteroaryl; substituted or unsubstituted, branched or unbranched arylalkyl; substituted or unsubstituted, branched or unbranched heteroarylalkyl; —C(═O)RB; —SORB; —SO2RB; or —C(RB)3; wherein each occurrence of RB is independently hydrogen; halogen; a protecting group; aliphatic; heteroaliphatic; acyl; aryl; heteroaryl; hydroxyl; alkoxy; aryloxy; amino; alkylamino; dialkylamino; or heteroaryloxy; or R2 and R3 may optionally be taken together with the intervening nitrogen to form a saturated or unsaturated, substituted or unsubstituted heterocyclic moiety; R4 is hydrogen, C1-6 aliphatic, or a protecting group; R5 is hydrogen, C1-6 aliphatic, or a protecting group; R6 is hydrogen; halogen; cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic; cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic; substituted or unsubstituted, branched or unbranched acyl; substituted or unsubstituted, branched or unbranched aryl; substituted or unsubstituted, branched or unbranched heteroaryl; —ORF; —C(═O)RF; —CO2RF; —C(═O)N(RF)2; —CN; —SCN; —SRF; —SORF; —SO2RF; —NO2; —N(RF)2; —NHC(O)RF; or —C(RF)3; wherein each occurrence of RF is independently hydrogen; halogen; a protecting group; aliphatic; heteroaliphatic; acyl; aryl moiety; heteroaryl; hydroxy; alkoxy; aryloxy; alkylthioxy; arylthioxy; amino; alkylamino; dialkylamino; heteroaryloxy; or heteroarylthioxy; and n is 0, 1, 2, or 3; wherein the compound of formula (I) is not one of the following: