4535-96-0Relevant articles and documents
Achiral Derivatives of Hydroxamate AR-42 Potently Inhibit Class i HDAC Enzymes and Cancer Cell Proliferation
Tng, Jiahui,Lim, Junxian,Wu, Kai-Chen,Lucke, Andrew J.,Xu, Weijun,Reid, Robert C.,Fairlie, David P.
supporting information, p. 5956 - 5971 (2020/06/05)
AR-42 is an orally active inhibitor of histone deacetylases (HDACs) in clinical trials for multiple myeloma, leukemia, and lymphoma. It has few hydrogen bond donors and acceptors but is a chiral 2-arylbutyrate and potentially prone to racemization. We report achiral AR-42 analogues incorporating a cycloalkyl group linked via a quaternary carbon atom, with up to 40-fold increased potency against human class I HDACs (e.g., JT86, IC50 0.7 nM, HDAC1), 25-fold increased cytotoxicity against five human cancer cell lines, and up to 70-fold less toxicity in normal human cells. JT86 was ninefold more potent than racAR-42 in promoting accumulation of acetylated histone H4 in MM96L melanoma cells. Molecular modeling and structure-activity relationships support binding to HDAC1 with tetrahydropyran acting as a hydrophobic shield from water at the enzyme surface. Such potent inhibitors of class I HDACs may show benefits in diseases (cancers, parasitic infections, inflammatory conditions) where AR-42 is active.
Design and synthesis of novel imidazoline derivatives with potent antihyperglycemic activity in a rat model of type 2 diabetes
Crane, Louis,Anastassiadou, Maria,Hage, Salome El,Stigliani, Jean Luc,Baziard-Mouysset, Genevieve,Payard, Marc,Leger, Jean Michel,Bizot-Espiard, Jean-Guy,Ktorza, Alain,Caignard, Daniel-Henri,Renard, Pierre
, p. 7419 - 7433 (2007/10/03)
Imidazoline derivatives have been reported to show antihyperglycemic activity in vivo. In the present study, we first showed that there was no correlation between the in vivo antidiabetic activity and the in vitro affinities for the I1/I2
Generation of 5- and 6-membered ring radicals by deoxygenation of alkoxy radicals
Kim, Sunggak,Oh, Dong Hyun
, p. 525 - 527 (2007/10/03)
A new approach, based on deoxygenation of alkoxyl radicals with triphenylphosphine, for the formation of 5- and 6-membered ring radicals from acyclic radical precursors is described.