Muraglia Ester, Altamura Sergio, Branca Danila, Cecchetti Ottavia, Ferrigno Federica, Orsale Maria Vittoria, Palumbi Maria Cecilia, Rowley Michael, Scarpelli Rita, Steinkühler Christian, Jones Philip
IRBM-Merck Research Laboratories Rome, Via Pontina km 30,600-Pomezia, 00040 Rome, Italy.
Bioorg Med Chem Lett. 2008 Dec 1;18(23):6083-7. doi: 10.1016/j.bmcl.2008.09.076. Epub 2008 Sep 24.
Trifluoroacetylthiophene carboxamides have recently been reported to be class II HDAC inhibitors, with moderate selectivity. Exploration of replacements for the carboxamide with bioisosteric pentatomic heteroaromatic like 1,3,4-oxadiazoles, 1,2,4-oxadiazoles and 1,3-thiazoles, led to the discovery that 2-trifluoroacetylthiophene 1,3,4-oxadiazole derivatives are very potent low nanomolar HDAC4 inhibitors, highly selective over class I HDACs (HDAC 1 and 3), and moderately stable in HCT116 cell culture.
三氟乙酰噻吩羧酰胺最近被报道为具有中等选择性的II类组蛋白去乙酰化酶（HDAC）抑制剂。用生物电子等排体五元杂环如1,3,4-恶二唑、1,2,4-恶二唑和1,3-噻唑取代羧酰胺进行探索，发现2-三氟乙酰噻吩1,3,4-恶二唑衍生物是非常有效的低纳摩尔HDAC4抑制剂，对I类HDAC（HDAC 1和3）具有高度选择性，并且在HCT116细胞培养中具有适度的稳定性。
