发现基于乙基酮的 HDACs1、2 和 3 选择性抑制剂，用于 HIV 潜伏再激活。
Discovery of ethyl ketone-based HDACs 1, 2, and 3 selective inhibitors for HIV latency reactivation.
机构信息
Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
Merck & Co., Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA.
出版信息
Bioorg Med Chem Lett. 2020 Jul 1;30(13):127197. doi: 10.1016/j.bmcl.2020.127197. Epub 2020 Apr 15.
A novel series of ethyl ketone based HDACs 1, 2, and 3 selective inhibitors have been identified with good enzymatic and cellular activity and high selectivity over HDACs 6 and 8. These inhibitors contain a spirobicyclic group in the amide region. Compound 13 stands out as a lead due to its good potency, high selectivity, and reasonable rat and dog PK. Compounds 33 and 34 show good potency and rat PK profiles as well.
已鉴定出一系列新型基于乙基酮的 HDAC1、2 和 3 选择性抑制剂，它们在酶和细胞水平上具有良好的活性，对 HDAC6 和 8 具有高选择性。这些抑制剂的酰胺区域含有螺环基团。化合物 13 因其良好的效力、高选择性和合理的大鼠和犬 PK 而脱颖而出。化合物 33 和 34 也具有良好的效力和大鼠 PK 特征。
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