127273-12-5Relevant articles and documents
A novel synthetic protocol for the synthesis of pulvinones, and naturally occurring Aspulvinone E, molecules of medicinal interest
Igglessi-Markopoulou, Olga,Katsamakas, Sotirios,Markopoulos, John,Prousis, Kyriakos C.
, (2021/11/22)
A novel two step methodology for readily accessible natural “pulvinone” derivatives in excellent yields has been developed starting from activated precursors, bearing a functionalized 1,3-dioxolane-2,4-diones (OCA’s), as dually protected-activated synthon
An Atropos Biphenyl Bisphosphine Ligand with 2,2′-tert-Butylmethylphosphino Groups for the Rhodium-Catalyzed Asymmetric Hydrogenation of Enol Esters
Jia, Jia,Fan, Dongyang,Zhang, Jian,Zhang, Zhenfeng,Zhang, Wanbin
supporting information, p. 3793 - 3800 (2018/09/20)
This is an update of our previous work concerning the development of Atropos biphenyl bisphosphine ligands. An unexpected Atropos structural property was confirmed by single crystal X-ray diffraction and this result is consistent with the computational calculations described in our previous work. This P-stereogenic bisphosphine ligand possessing a biphenyl backbone and 2,2′-tert-butylmethylphosphino groups has been applied to the Rh-catalyzed asymmetric hydrogenation of enol esters, which has not been widely studied and can be used for the synthesis of several important bioactive compounds. Although there is room for further improvement in enantioselectivity, the results reported herein provide a further understanding of such types of ligands. (Figure presented.).
Design, synthesis, and biological evaluation of substrate-competitive inhibitors of C-terminal Binding Protein (CtBP)
Korwar, Sudha,Morris, Benjamin L.,Parikh, Hardik I.,Coover, Robert A.,Doughty, Tyler W.,Love, Ian M.,Hilbert, Brendan J.,Royer, William E.,Kellogg, Glen E.,Grossman, Steven R.,Ellis, Keith C.
, p. 2707 - 2715 (2016/06/08)
C-terminal Binding Protein (CtBP) is a transcriptional co-regulator that downregulates the expression of many tumor-suppressor genes. Utilizing a crystal structure of CtBP with its substrate 4-methylthio-2-oxobutyric acid (MTOB) and NAD+ as a guide, we have designed, synthesized, and tested a series of small molecule inhibitors of CtBP. From our first round of compounds, we identified 2-(hydroxyimino)-3-phenylpropanoic acid as a potent CtBP inhibitor (IC50 = 0.24 μM). A structure-activity relationship study of this compound further identified the 4-chloro- (IC50 = 0.18 μM) and 3-chloro- (IC50 = 0.17 μM) analogues as additional potent CtBP inhibitors. Evaluation of the hydroxyimine analogues in a short-term cell growth/viability assay showed that the 4-chloro- and 3-chloro-analogues are 2-fold and 4-fold more potent, respectively, than the MTOB control. A functional cellular assay using a CtBP-specific transcriptional readout revealed that the 4-chloro- and 3-chloro-hydroxyimine analogues were able to block CtBP transcriptional repression activity. This data suggests that substrate-competitive inhibition of CtBP dehydrogenase activity is a potential mechanism to reactivate tumor-suppressor gene expression as a therapeutic strategy for cancer.
