Tranylcypromine and 6-trifluoroethyl thienopyrimidine hybrid as LSD1 inhibitor.


College of Chemistry, Chemical Engineering and Environmental Engineering, Liaoning Shihua University, Dandong Lu West 1, Fushun 113001, PR China. Electronic address: [Email]


Tranylcypromine moiety extracted from LSD1 inhibitors and 6-trifluoroethyl thienopyrimidine moiety from menin-MLL1 PPI inhibitors were merged to give new chemotypes for medicinal chemistry study. Among 15 new compounds prepared in this work, some exhibited nanomolar LSD1 activity and good selectivity over MAO-A/B, low micromolar menin-MLL1 PPI inhibitory activity, as well as submicromolar MV4-11 antiprofilative activities. Intracellular LSD1 engagement of compounds with higher enzymatic and antiproliferative activities was confirmed by CD86 mRNA up-regulation experiments.


LSD1 inhibitor,MV4-11 antiproliferative activity,Menin-MLL1 protein-protein interaction inhibitor,Structure activity relationship,Tranylcypromine,