Huhtiniemi Tero, Suuronen Tiina, Rinne Valtteri M, Wittekindt Carsten, Lahtela-Kakkonen Maija, Jarho Elina, Wallén Erik A A, Salminen Antero, Poso Antti, Leppänen Jukka
Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, 70211 Kuopio, Finland.
J Med Chem. 2008 Aug 14;51(15):4377-80. doi: 10.1021/jm800639h. Epub 2008 Jul 22.
A new inhibitor for human sirtuin type proteins 1 and 2 (SIRT1 and SIRT2) was discovered through virtual database screening in search of new scaffolds. A series of compounds was synthesized based on the hit compound (3-[[3-(4-tert-butylphenyl)1,2,4-oxadiazole-5-carbonyl]amino]-1-[3-(trifluoromethyl)phenyl]thiourea). The most potent compound in the series was nearly as potent as the reference compound (6-chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide).
通过虚拟数据库筛选寻找新的骨架，发现了一种针对人类1型和2型沉默调节蛋白（SIRT1和SIRT2）的新型抑制剂。基于命中化合物（3-[[3-(4-叔丁基苯基)-1,2,4-恶二唑-5-羰基]氨基]-1-[3-(三氟甲基)苯基]硫脲）合成了一系列化合物。该系列中最有效的化合物几乎与参考化合物（6-氯-2,3,4,9-四氢-1H-咔唑-1-甲酰胺）一样有效。
