A sub-milligram-synthesis protocol for in vitro screening of HDAC11 inhibitors. Issue 10 (15th May 2016)

• Record Type: Journal Article
• Authors: Tian, Yinping; Jin, Jin; Wang, Congying; Lv, Wenhui; Li, Xuewei; Che, Xiaona; Gong, Yanchao; Li, Yanjun; Li, Quanli; Hou, Jingli; Wang, Peng G.; Shen, Jie
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 10(2016)
• Page Start: 2434
• Page End: 2437
• Publication Date: 2016-05-15
• Subjects: Sub-milligram-synthesis -- HDAC11 -- Solid phase synthesis -- UV quantification -- Unconjugated chromophore; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2016.03.116
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: This work demonstrated the high efficiency of a sub-milligram-synthesis based medicinal chemistry method. Totally 72 compounds, consisting a tri-substituted pyrrolidine core, were prepared. Around 0.1 mg of each compound was solid-phase synthesized. Based on the additive property of UV absorptions of unconjugated chromophores of a molecule, these compounds were quantified by UV measurement. A hit, whose IC50 value was 1.2 μM in HDAC11 inhibition assays, highlights the applicability of the approach reported here in future optimization works.