RESUMO
An efficient strategy for the synthesis of complex small molecules from simple building blocks is presented. Key steps of the strategy include tandem Petasis and Diels-Alder reactions, and divergent complexity-generating cyclization cascades from a key dialdehyde intermediate. The methodology is validated through the synthesis of a representative compound set, which has been used in the production of 1617 molecules for the European Lead Factory.
RESUMO
The effect of picolinic acid and hydroxyquinolines in intestinal zinc absorption of cattle was studied. In contrast to reports of the absorption in rat and in man, picolinic acid did not enhance zinc absorption in cattle. In two calves suffering from Adema disease, the bovine parallel to Acrodermatitis enteropathica, hydroxyquinoline supplementation resulted in an increase in intestinal 65Zn absorption, while picolinic acid had no such effect. The results may indicate a difference in the zinc absorption mechanism between cattle and other species.
Assuntos
Bovinos/metabolismo , Absorção Intestinal/efeitos dos fármacos , Ácidos Picolínicos/farmacologia , Zinco/metabolismo , Acrodermatite/tratamento farmacológico , Acrodermatite/veterinária , Animais , Doenças dos Bovinos/tratamento farmacológico , Dieta , Hidroxiquinolinas/uso terapêutico , Masculino , Zinco/sangueRESUMO
In two calves with the genetic defect A46 (Adema disease) intestinal absorption of 65Zn was increased during a period of oral treatment with oxychinolines. Oral supplementation with zinc oxide resulted in extremely high plasma zinc concentrations and a moderate increase in 65Zn absorption.
Assuntos
Doenças dos Bovinos/tratamento farmacológico , Hidroxiquinolinas/uso terapêutico , Absorção Intestinal/efeitos dos fármacos , Síndromes de Malabsorção/veterinária , Oxiquinolina/uso terapêutico , Administração Oral , Animais , Bovinos , Doenças dos Bovinos/genética , Síndromes de Malabsorção/tratamento farmacológico , Síndromes de Malabsorção/genética , Oxiquinolina/administração & dosagem , Oxiquinolina/farmacologia , Zinco/sangue , Óxido de Zinco/uso terapêuticoAssuntos
Doenças dos Bovinos/metabolismo , Absorção Intestinal , Ceratose/veterinária , Paraceratose/veterinária , Zinco/metabolismo , Animais , Bovinos , Doenças dos Bovinos/sangue , Doenças dos Bovinos/genética , Feminino , Masculino , Paraceratose/sangue , Paraceratose/genética , Paraceratose/metabolismo , Zinco/sangue , Zinco/deficiênciaRESUMO
Adema disease and acrodermatitis enteropathica, two parallel syndromes in calves of Friesian descent and in man, are described. Both are congenital zinc deficiency disorders with a lethal course if left untreated. Complete recovery follows oral zinc therapy. Symptoms and findings are set out in Table I. Diseased calves may serve as animal models for further studies on acrodermatitis enteropathica and the biological role of zinc.