Search

New enantiomerically pure 1,3-bis(2’-oxazolinyl)ferrocenes have been synthesized in good yields starting from 1,3-ferrocene dicarboxylic acid. Moreover, the possibility of performing a regioselective lithiation in position 2 of the disubstituted cyclopentadienyl ring of these compounds has been demonstrated.

The title compound, [Pd(C2H3O2)(C18H15P)(C12H11N2O)]·CH2Cl2, crystallizes readily from a mixture of di­chloro­methane and light petroleum. The structure is one of few examples of palladacycles that incorporate the N-substituent in five-membered-ring heterocycles [Nonoyama & Nakajima (1998). Polyhedron, 18, 533–543].

International audience; Fusion between the viral and target cell membranes is an obligatory step for the infectivity of all enveloped virus, and blocking this process is a clinically validated therapeutic strategy.Viral fusion is driven by specialized proteins which, although specific to each virus, act through a common mechanism, the formation of a complex between two heptad repeat (HR) regions. The HR regions are initially separated in an intermediate termed "prehairpin", which bridges the viral and cell membranes, and then fold onto each other to form a 6-helical bundle (6HB), driving the two membranes to fuse. HR-derived peptides can inhibit viral infectivity by binding to the prehairpin intermediate and preventing its transition to the 6HB.The antiviral activity of HR-derived peptides differs considerably among enveloped viruses. For weak inhibitors, potency can be increased by peptide engineering strategies, but sequence-specific optimization is time-consuming. In seeking ways to increase potency without changing the native sequence, we previously reported that attachment to the HR peptide of a cholesterol group ("cholesterol-tagging") dramatically increases its antiviral potency, and simultaneously increases its half-life in vivo. We show here that antiviral potency may be increased by combining cholesterol-tagging with dimerization of the HR-derived sequence, using as examples human parainfluenza virus, Nipah virus, and HIV-1. Together, cholesterol-tagging and dimerization may represent strategies to boost HR peptide potency to levels that in some cases may be compatible with in vivo use, possibly contributing to emergency responses to outbreaks of existing or novel viruses.

OBJECTIVE Oxyntomodulin (OXM) is a glucagon-like peptide 1 (GLP-1) receptor (GLP1R)/glucagon receptor (GCGR) dual agonist peptide that reduces body weight in obese subjects through increased energy expenditure and decreased energy intake. The metabolic effects of OXM have been attributed primarily to GLP1R agonism. We examined whether a long acting GLP1R/GCGR dual agonist peptide exerts metabolic effects in diet-induced obese mice that are distinct from those obtained with a GLP1R-selective agonist. RESEARCH DESIGN AND METHODS We developed a protease-resistant dual GLP1R/GCGR agonist, DualAG, and a corresponding GLP1R-selective agonist, GLPAG, matched for GLP1R agonist potency and pharmacokinetics. The metabolic effects of these two peptides with respect to weight loss, caloric reduction, glucose control, and lipid lowering, were compared upon chronic dosing in diet-induced obese (DIO) mice. Acute studies in DIO mice revealed metabolic pathways that were modulated independent of weight loss. Studies in Glp1r−/− and Gcgr−/− mice enabled delineation of the contribution of GLP1R versus GCGR activation to the pharmacology of DualAG. RESULTS Peptide DualAG exhibits superior weight loss, lipid-lowering activity, and antihyperglycemic efficacy comparable to GLPAG. Improvements in plasma metabolic parameters including insulin, leptin, and adiponectin were more pronounced upon chronic treatment with DualAG than with GLPAG. Dual receptor agonism also increased fatty acid oxidation and reduced hepatic steatosis in DIO mice. The antiobesity effects of DualAG require activation of both GLP1R and GCGR. CONCLUSIONS Sustained GLP1R/GCGR dual agonism reverses obesity in DIO mice and is a novel therapeutic approach to the treatment of obesity.

A nitrogen-containing superbase such as TMG was found to be an effective catalyst for the reaction between N-diphenylphosphinoyl imines and nitroalkanes. Exploiting a protocol that avoids the use of any solvent also during workup procedure, we synthesized a series of beta-nitroamines in excellent yields and high diastereomeric ratios. These results, combined with the capability of the indium in conjunction with Zn as the stoichiometric reducing agent to perform in aqueous medium reduction of the nitro group under mild reaction conditions, led us to devise a three-step, one-pot synthesis of a range of 1,2-diamines, making use of environmentally friendly procedures in the various steps.

The title compound, [Pd(C11H13N2)Cl(C18H15P)]·CH2Cl2, crystallizes readily from a mixture of di­chloro­methane and light petroleum. The structure is one of few examples of palladacycles that incorporate the N-substituent in five-membered ring heterocycles [Nonoyama & Nakajima (1998). Polyhedron 18, 533–543.].

Enantiomerically pure 2-hydroxyalkyl, 2-aminoalkyl and 2-iminoalkyl ferrocenyl p-tolylsulfides are easily prepared in good yields and with complete diastereocontrol from (S)-(2-p- tolylthio)ferrocencarboxyaldehyde. This aldehyde provides also an easy access to the first enantiomerically pure planar chiral ferrocenyl cyanohydrin. The absolute configuration of the new stereocenters has been determined by single-crystal X-ray analysis.