2243-76-7Relevant articles and documents
Syn and anti conformations in 2-hydroxy-5-[(E)-(4-nitrophenyl)diazenyl] benzoic acid and two related salts
Yatsenko, Alexandr V.,Paseshnichenko, Ksenia A.
, p. 493 - 497 (2014)
The crystal structures of 2-hydroxy-5-[(E)-(4-nitrophenyl)diazenyl]benzoic acid, C13H9N3O5, (I), ammonium 2-hydroxy-5-[(E)-phenyldiazenyl]benzoate, NH4 + C13H 9N2O3 -, (II), and sodium 2-hydroxy-5-[(E)-(4-nitrophenyl)diazenyl]benzoate trihydrate, Na+ C13H8N3O5 - 3H2O, (III), have been determined using single-crystal X-ray diffraction. In (I) and (III), the phenyldiazenyl and carboxylic acid/carboxylate groups are in an anti orientation with respect to each other, which is in accord with the results of density functional theory (DFT) calculations, whereas in (II), the anion adopts a syn conformation. In (I), molecules form slanted stacks along the [100] direction. In (II), anions form bilayers parallel to (010), the inner part of the bilayers being formed by the benzene rings, with the -OH and -COO - substituents on the bilayer surface. The NH4+ cations in (II) are located between the bilayers and are engaged in numerous N-H?O hydrogen bonds. In (III), anions form layers parallel to (001). Both Na+ cations have a distorted octahedral environment, with four octahedra edge-shared by bridging water O atoms, forming [Na4(H 2O)12]4+ units.
Identification of the subtype-selective Sirt5 inhibitor balsalazide through systematic SAR analysis and rationalization via theoretical investigations
Bracher, Franz,Dietschreit, Johannes C. B.,Ghazy, Ehab,Glas, Carina,Jung, Manfred,Ochsenfeld, Christian,Sippl, Wolfgang,Urban, Lars,W?ssner, Nathalie
supporting information, (2020/08/28)
We report here an extensive structure-activity relationship study of balsalazide, which was previously identified in a high-throughput screening as an inhibitor of Sirt5. To get a closer understanding why this compound is able to inhibit Sirt5, we initially performed docking experiments comparing the binding mode of a succinylated peptide as the natural substrate and balsalazide with Sirt5 in the presence of NAD+. Based on the evidence gathered here, we designed and synthesized 13 analogues of balsalazide, in which single functional groups were either deleted or slightly altered to investigate which of them are mandatory for high inhibitory activity. Our study confirms that balsalazide with all its given functional groups is an inhibitor of Sirt5 in the low micromolar concentration range and structural modifications presented in this study did not increase potency. While changes on the N-aroyl-β-alanine side chain eliminated potency, the introduction of a truncated salicylic acid part minimally altered potency. Calculations of the associated reaction paths showed that the inhibition potency is very likely dominated by the stability of the inhibitor-enzyme complex and not the type of inhibition (covalent vs. non-covalent). Further in-vitro characterization in a trypsin coupled assay determined that the tested inhibitors showed no competition towards NAD+ or the synthetic substrate analogue ZKsA. In addition, investigations for subtype selectivity revealed that balsalazide is a subtype-selective Sirt5 inhibitor, and our initial SAR and docking studies pave the way for further optimization.
The in situ generation and reactive quench of diazonium compounds in the synthesis of azo compounds in microreactors
Akwi, Faith M.,Watts, Paul
, p. 1987 - 2004 (2016/10/05)
In this paper, a micro-fluidic optimized process for the continuous flow synthesis of azo compounds is presented. The continuous flow synthesis of Sudan II azo dye was used as a model reaction for the study. At found optimal azo coupling reaction temperature and pH an investigation of the optimum flow rates of the reactants for the diazotization and azo coupling reactions in Little Things Factory-MS microreactors was performed. A conversion of 98% was achieved in approximately 2.4 minutes and a small library of azo compounds was thus generated under these reaction conditions from couplers with aminated or hydroxylated aromatic systems. The scaled up synthesis of these compounds in PTFE tubing (i.d. 1.5 mm) was also investigated, where good reaction conversions ranging between 66-91% were attained.
