Compositions comprising thienopyrimidine and thienopyridine compounds and methods of use thereof

摘要

The present disclosure relates generally to thienopyrimidine and thienopyridine compounds and methods of use thereof. In particular embodiments, the present disclosure provides compositions comprising thienopyrimidine and thienopyridine compounds of Formula 2:;
and methods of use to inhibit the interaction of menin with MLL1, MLL2 and MLL-fusion oncoproteins.

主权项

1. A compound of Formula 2: or a pharmaceutically acceptable salt thereof, wherein: each of R1 and R2 is independently H, alkyl, substituted alkyl, alcohol, ether, amine, thioalkyl, halogen, ketone, carbocyclic ring, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, thiol, disulfide, sulfoxide, or sulfone; Y is N, C—H, or C—Ra; Ra is alkyl, heteroalkyl, alkyl-substituted aryl, substituted alkyl, alcohol, ether, amino, cyano, aldehyde, heterocycloalkyl, or aromatic group; L is alkylene, oxalkylene, or absent; wherein when L is absent the bonds attached to L do not exist; Q is alkylene or heteroalkylene; each R3 is independently H, alkyl, substituted alkyl, alcohol, ether, amine, thioalkyl, halogen, ketone, carbocyclic ring, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, or substituted heterocycloalkyl; n is 1, 2, 3, or 4; and Z is CHR4SO2R5 or —NR4SO2R5, wherein R4 is H, alkyl, substituted alkyl, alcohol, ether, amine, or carbocyclic ring and R5 is H, alkyl, substituted alkyl, alcohol, ether, amine, thioalkyl, ketone, carbocyclic ring, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, or substituted heterocycloalkyl.