Cycloalkane analogues of sinefungin as EHMT1/2 inhibitors

A series of cycloalkyl substituted analogues of the natural product sinefungin lacking the amino-acid moiety was designed and synthesized. Two stereoisomers (6-R and 6-S) were separated and their bioactivities examined against EHMT1/2. Of which, compound 14d showed an inhibitory activity against EHMT1/2 (88.9%, IC50 = 21.8 mu M for EHMT1 and 77.6%, IC50 = 39.6 mu M for EHMT2, respectively) similar to that of sinefungin (100.0%, IC50 = 28.4 mu M for EHMT1 and 79.5%, IC50 = 30.1 mu M for EHMT2, respectively). Further studies against other methyltransferases such as PRMT1 showed no activity except that 12d displayed about 20% inhibition. (C) 2017 Elsevier Ltd. All rights reserved.