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 4b:;
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 4b: or a pharmaceutically acceptable salt thereof, wherein each of R1, R7, R3, R4, R5, R6, R7, and R is independently H, alkyl, substituted alkyl, cycloalkyl, substituted cycloalkyl, alkene, alkyne, heteroalkyl, alcohol, diol, substituted diol, ether, amine, alkylamine, thiol, thioalkyl, halogen, carbocyclic ring, aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, aldehyde; ketone, CO—(CH2)1-6—H, CO-ethenyl, CO-propenyl, CO-ethynyl, CO-propynyl, CO—(CH2)1-6-aryl, CO—(CH2)1-6-heteroaryl, CO—(CH2)1-3-trifluoromethane, CO—(CH2)1-6-cycloalkane, carboxylic acid, alkylcarboxylic acid, ester, alkylester, amide, CO-amino-dialkyl, alkylamide; sulfoxide, sulfone, SO2—(CH2)1-6—H, SO2-alkenyl, SO2-alkynyl, SO2NH2, SO2—NH-alkyl, SO2-amino-dialkyl, sulfinic acid, cyano, alkylcyano, methylcarbonitrile, cyanate, thiocyanate, azide, or phosphate; wherein R6 is present at one or more positions of the indole; Y is N, C—H, or Ra is alkyl, substituted alkyl, Amy, cycloalkyl, heteroalkyl, alkyl-substituted aryl, substituted aryl, aromatic heterocycle, non-aromatic heterocycle, alcohol, ether, amine, cyano, sulfonyl, aldehyde, or aromatic group; L is alkylene, oxalkylene, or absent; wherein when L is absent the bonds attached to L do not exist; and each of E and G is independently N or C, wherein each of E and G is independently optionally substituted with R6.