RESUMO
The use of graphene derivatives as supports improves the properties of heterogeneous catalysts, with graphene oxide (GO) being the most frequently employed. To explore greener possibilities as well as to get some insights into the role of the different graphenic supports (GO, rGO, carbon black, and graphite nanoplatelets), we prepared, under the same standard conditions, a variety of heterogeneous Cu catalysts and systematically evaluated their composition and catalytic activity in azide-alkyne cycloadditions as a model reaction. The use of sustainable graphite nanoplatelets (GNPs) afforded a stable CuI catalyst with good recyclability properties, which are compatible with flow conditions, and able to catalyze other reactions such as the regio- and stereoselective sulfonylation of alkynes (addition reaction) and the Meerwein arylation (single electron transfer process).
RESUMO
Two closely related diaryl acylsulfonamides were recently reported as potent antitumor agents against a broad spectrum of human tumor xenografts (colon, lung, breast, ovary, and prostate) in nude mice. Especially intriguing was their activity against colorectal cancer xenografts. In this paper, rapid parallel synthesis along with traditional medicinal chemistry techniques were used to quickly delineate the structure-activity relationships of the substitution patterns in both phenyl rings of the acylsufonamide anti-proliferative scaffold. Although the molecular target of the compounds remains unclear, we determined that the vascular endothelial growth factor-dependent human umbilical vein endothelial cells assay in combination with a soft agar disk diffusion assay allowed for optimization of potency in the series. The pharmacokinetic properties and in vivo activity in an HCT116 xenograft model are reported for representative compounds.
Assuntos
Antineoplásicos/síntese química , Sulfonamidas/síntese química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Ensaios de Seleção de Medicamentos Antitumorais , Endotélio Vascular/citologia , Endotélio Vascular/efeitos dos fármacos , Feminino , Meia-Vida , Humanos , Técnicas In Vitro , Camundongos , Camundongos Nus , Relação Quantitativa Estrutura-Atividade , Ratos , Ratos Endogâmicos F344 , Sulfonamidas/química , Sulfonamidas/farmacologia , Transplante Heterólogo , Veias Umbilicais/citologia , Fator A de Crescimento do Endotélio Vascular/farmacologia , Fator A de Crescimento do Endotélio Vascular/fisiologiaRESUMO
Reduced graphene oxide (rGO) has been used as a support for piperazine to provide a heterogeneous bifunctional organocatalyst (rGO-NH) that is able to efficiently promote vintage organic transformations such as Knoevenagel, Michael and aldol reactions. The obtained results suggest a significant role of the support in the course of these reactions.
RESUMO
An automated liquid-liquid extraction workstation has been developed. This module processes up to 96 samples in an automated and parallel mode avoiding the time-consuming and intensive sample manipulation during the workup process. To validate the workstation, a highly automated and chromatography-free synthesis of differentially substituted quinazolin-4(3H)-ones with two diversity points has been carried out using isatoic anhydride as starting material.
Assuntos
Automação , Cromatografia Líquida/instrumentação , Quinazolinonas/síntese química , Espectroscopia de Ressonância Magnética , Espectrometria de Massas por Ionização por ElectrosprayRESUMO
Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes.
Assuntos
Cinamatos/farmacologia , Diabetes Mellitus Tipo 2/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/agonistas , Animais , Glicemia/metabolismo , Cinamatos/administração & dosagem , Cinamatos/química , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Ratos , Ratos Zucker , Relação Estrutura-Atividade , Triglicerídeos/sangueRESUMO
The combination of 1D and 2D high-resolution magic angle spinning NMR experiments led to the assignment of the proton and carbon resonances for several disubstituted benzoates bound to a polystyrene resin through a Wang linker. It is shown that the signal corresponding to the methylene protons of the linker can be utilized to monitor the solid-phase reactions and determine the loading of the compounds on the resin.
RESUMO
Numerous analogues of the naturally occurring antibiotic althiomycin have been synthesised exploiting both total- and semi-synthetic methodologies. The antibacterial activity of these derivatives has been determined in whole cell assays and indicates the natural product exhibits a restricted SAR.