68383-86-8Relevant articles and documents
Regioselective syntheses of 3-hydroxy-4-aryl-3,4,5-trihydro-2H-benzo[b][1,4]diazepin-2(1H)-ones and 3-benzylquinoxalin-2(1H)-ones from arylglycidates when exposed to 1,2-diaminobenzenes
Mamedov, Vakhid A.,Mamedova, Vera L.,Syakaev, Victor V.,Voronina, Julia K.,Mahrous, Essam M.,Korshin, Dmitry E.,Latypov, Shamil K.,Sinyashin, Oleg G.
, (2020/09/10)
Representatives of two pharmacologically significant classes of compounds – 3-hydroxy-4-aryl-3,4,5-trihydro-2H-benzo[b][1,4]diazepin-2(1H)-ones and 3-benzylquinoxalin-2(1H)-ones – obtained in reactions of 1,2-diaminobenzenes with methyl 3-arylglycidates in boiling acetic acid. Substituents in arylglycidates determine the direction of processes. Electron withdrawing substituents (NO2), halogen atoms (Cl, Br, F), as well as the absence of substituents, provide the formation of benzo[b][1,4]diazepin-2(1H)-one derivatives, and electron donating groups (OMe, Me) contribute to the formation of 3-benzylquinoxalin-2(1H)-ones. As a result, a new rare representatives of 3-hydroxy-4-aryl-3,4,5-trihydro-2H-benzo[b][1,4]diazepin-2(1H)-ones were obtained and a new method for producing 3-benzylquinoxalin-2(1H)-ones has been proposed.
Evaluation of α-hydroxycinnamic acids as pyruvate carboxylase inhibitors
Burkett, Daniel J.,Wyatt, Brittney N.,Mews, Mallory,Bautista, Anson,Engel, Ryan,Dockendorff, Chris,Donaldson, William A.,St. Maurice, Martin
, p. 4041 - 4047 (2019/08/26)
Through a structure-based drug design project (SBDD), potent small molecule inhibitors of pyruvate carboxylase (PC) have been discovered. A series of α-keto acids (7) and α-hydroxycinnamic acids (8) were prepared and evaluated for inhibition of PC in two assays. The two most potent inhibitors were 3,3′-(1,4-phenylene)bis[2-hydroxy-2-propenoic acid] (8u) and 2-hydroxy-3-(quinoline-2-yl)propenoic acid (8v) with IC50 values of 3.0 ± 1.0 μM and 4.3 ± 1.5 μM respectively. Compound 8v is a competitive inhibitor with respect to pyruvate (Ki = 0.74 μM) and a mixed-type inhibitor with respect to ATP, indicating that it targets the unique carboxyltransferase (CT) domain of PC. Furthermore, compound 8v does not significantly inhibit human carbonic anhydrase II, matrix metalloproteinase-2, malate dehydrogenase or lactate dehydrogenase.
5-Benzylidene-4-oxazolidinones potently inhibit biofilm formation in Methicillin-resistant Staphylococcus aureus
Edwards, Grant A.,Shymanska, Nataliia V.,Pierce, Joshua G.
supporting information, p. 7353 - 7356 (2017/07/11)
Investigation into the biological function of 5-benzylidene-4-oxazolidinones revealed dose-dependent inhibition of biofilm formation in Methicillin-resistant S. aureus (MRSA). This structurally unusual class of small molecules inhibit up to 89% of biofilm formation with IC50 values as low as 0.78 μM, and disperse pre-formed biofilms with IC50 values as low as 4.7 μM. Together, these results suggest that 4-oxazolidinones represent new chemotypes to enable the study of bacterial biofilms with small molecule chemical probes.
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.
