Design and evaluation of novel glutaminase inhibitors

作者：McDermott Lee A^*; Iyer Prema; Vernetti Larry; Rimer Shawn; Sun Jingran; Boby Melissa; Yang Tianyi; Fioravanti Michael; O'Neill Jason; Wang Liwei; Drakes Dylan; Katt William; Huang Qingqiu; Cerione Richard

来源：Bioorganic & Medicinal Chemistry, 2016, 24(8): 1819-1839.

DOI：10.1016/j.bmc.2016.03.009

• GAC
• Novel glutaminase inhibitors
• BPTES
• CB-839

A novel set of GAC (kidney glutaminase isoform C) inhibitors able to inhibit the enzymatic activity of GAC and the growth of the triple negative MDA-MB-231 breast cancer cells with low nanomolar potency is described. Compounds in this series have a reduced number of rotatable bonds, improved ClogPs, microsomal stability and ligand efficiency when compared to the leading GAC inhibitors BPTES and CB-839. Property improvements were achieved by the replacement of the flexible n-diethylthio or the n-butyl moiety present in the leading inhibitors by heteroatom substituted heterocycloalkanes.

• 出版日期2016-4-15