Upton Kristen, Meyers Matthew, Thorsell Ann-Gerd, Karlberg Tobias, Holechek Jacob, Lease Robert, Schey Garrett, Wolf Emily, Lucente Adrianna, Schüler Herwig, Ferraris Dana
McDaniel College, 2 College Hill, Westminster, MD 21157, United States.
Karolinska Institutet, Department of Medical Biochemistry and Biophysics, Scheeles väg 2, S-17177 Stockholm, Sweden.
Bioorg Med Chem Lett. 2017 Jul 1;27(13):2907-2911. doi: 10.1016/j.bmcl.2017.04.089. Epub 2017 Apr 29.
A series of (Z)-4-(3-carbamoylphenylamino)-4-oxobut-2-enyl amides were synthesized and tested for their ability to inhibit the mono-(ADP-ribosyl)transferase, PARP14 (a.k.a. BAL-2; ARTD-8). Two synthetic routes were established for this series and several compounds were identified as sub-micromolar inhibitors of PARP14, the most potent of which was compound 4t, IC=160nM. Furthermore, profiling other members of this series identified compounds with >20-fold selectivity over PARP5a/TNKS1, and modest selectivity over PARP10, a closely related mono-(ADP-ribosyl)transferase.
合成了一系列(Z)-4-(3-氨甲酰基苯基氨基)-4-氧代丁-2-烯酰胺，并测试了它们抑制单(ADP-核糖基)转移酶PARP14（又名BAL-2；ARTD-8）的能力。为该系列化合物建立了两条合成路线，并鉴定出几种化合物为PARP14的亚微摩尔抑制剂，其中最有效的是化合物4t，IC=160 nM。此外，对该系列其他成员进行分析，鉴定出对PARP5a/TNKS1具有>20倍选择性、对密切相关的单(ADP-核糖基)转移酶PARP10具有适度选择性的化合物。
