27798-39-6Relevant articles and documents
Diflunisal Derivatives as Modulators of ACMS Decarboxylase Targeting the Tryptophan-Kynurenine Pathway
Yang, Yu,Borel, Timothy,De Azambuja, Francisco,Johnson, David,Sorrentino, Jacob P.,Udokwu, Chinedum,Davis, Ian,Liu, Aimin,Altman, Ryan A.
, p. 797 - 811 (2021/01/13)
In the kynurenine pathway for tryptophan degradation, an unstable metabolic intermediate, α-amino-β-carboxymuconate-?-semialdehyde (ACMS), can nonenzymatically cyclize to form quinolinic acid, the precursor for de novo biosynthesis of nicotinamide adenine dinucleotide (NAD+). In a competing reaction, ACMS is decarboxylated by ACMS decarboxylase (ACMSD) for further metabolism and energy production. Therefore, the inhibition of ACMSD increases NAD+ levels. In this study, an Food and Drug Administration (FDA)-approved drug, diflunisal, was found to competitively inhibit ACMSD. The complex structure of ACMSD with diflunisal revealed a previously unknown ligand-binding mode and was consistent with the results of inhibition assays, as well as a structure-activity relationship (SAR) study. Moreover, two synthesized diflunisal derivatives showed half-maximal inhibitory concentration (IC50) values 1 order of magnitude better than diflunisal at 1.32 ± 0.07 μM (22) and 3.10 ± 0.11 μM (20), respectively. The results suggest that diflunisal derivatives have the potential to modulate NAD+ levels. The ligand-binding mode revealed here provides a new direction for developing inhibitors of ACMSD.
Feedstocks to Pharmacophores: Cu-Catalyzed Oxidative Arylation of Inexpensive Alkylarenes Enabling Direct Access to Diarylalkanes
Vasilopoulos, Aristidis,Zultanski, Susan L.,Stahl, Shannon S.
supporting information, p. 7705 - 7708 (2017/06/20)
A Cu-catalyzed method has been identified for selective oxidative arylation of benzylic C-H bonds with arylboronic esters. The resulting 1,1-diarylalkanes are accessed directly from inexpensive alkylarenes containing primary and secondary benzylic C-H bonds, such as toluene or ethylbenzene. All catalyst components are commercially available at low cost, and the arylboronic esters are either commercially available or easily accessible from the commercially available boronic acids. The potential utility of these methods in medicinal chemistry applications is highlighted.
Synthesis of structurally diverse diarylketones through the diarylmethyl sp3 C-H oxidation
He, Chao,Zhang, Xiaohui,Huang, Ruofeng,Pan, Jing,Li, Jiaqiang,Ling, Xuege,Xiong, Yan,Zhu, Xiangming
supporting information, p. 4458 - 4462 (2014/08/05)
Under open-flask conditions, an efficient method to assemble a series of diversely functionalized diarylketones in the presence of commercially available NBS has been developed. Yields of up to 99% have been achieved employing diarylmethanes as starting material. Based on 18O-labeled experiment, the addition of stoichiometric water eventually leads to excellent yields in all carbonylation cases.
