58465-46-6Relevant academic research and scientific papers
Inhibitors of fumarylacetoacetate hydrolase domain containing protein 1 (Fahd1)
Eder, Manuel Philip,Gstach, Hubert,Jansen-Dürr, Pidder,Klapec, Patrycia,Liedl, Klaus R.,Loeffler, Johannes R.,Monteleone, Stefania,Weiss, Alexander K. H.,Wurzer, Richard,von Grafenstein, Susanne
, (2021/08/26)
FAH domain containing protein 1 (FAHD1) acts as oxaloacetate decarboxylase in mitochondria, contributing to the regulation of the tricarboxylic acid cycle. Guided by a high-resolution X-ray structure of FAHD1 liganded by oxalate, the enzymatic mechanism of substrate processing is analyzed in detail. Taking the chemical features of the FAHD1 substrate oxaloacetate into account, the potential inhibitor structures are deduced. The synthesis of drug-like scaffolds afforded first-generation FAHD1-inhibitors with activities in the low micromolar IC50 range. The investigations disclosed structures competing with the substrate for binding to the metal cofactor, as well as scaffolds, which may have a novel binding mode to FAHD1.
USE OF SUBSTITUTED 2-PHENYLBENZIMIDAZOLES AS MEDICAMENTS
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Page/Page column 37, (2010/02/07)
The invention relates to the use of a substituted 2-phenylbenzimidazole of formula (I), where R1, R2, R3, R4, R5 and m have the meanings given in the claims, for the production of a medicament for the treatment or prevention of diseases in which glucagon receptors are implicated and novel compounds of formula (I), where R1 is a group of formula (II).
Rational design and binding of modified cell-wall peptides to vancomycin-group antibiotics: Factorising free energy contributions to binding
Holroyd, Stephen E.,Groves, Patrick,Searle, Mark S.,Gerhard, Ute,Williams, Dudley H.
, p. 9171 - 9182 (2007/10/02)
Modified cell-wall peptides have been rationally designed and studied in a semi-quantitative approach to factorising free energy contributions in binding to vancomycin-group antibiotics in aqueous solution. Binding energies for succinyl and fumaryl-D-Ala dipeptides. and N-oxalyl-γ-aminobutyric acid analogues, are compared with binding energies for the natural substrate N-Ac-D-Ala-D-Ala, and the truncated mono-peptide N-Ac-D-Ala. We estimate the binding energy of the N-terminal carboxyl group, by four independent analyses, to he -(14 to 17)±7 kJ mol-1 when differences in ligand binding energies are corrected for differences in contributions from the "cost" of restricting rotations and "benefits" of hydrophobic interactions. The carboxylate interaction comprises both a charged - COO-...HN hydrogen bond plus face to face π-stacking between the carboxylate group and an aromatic ring in the antibiotic binding pocket.
