A QSAR study on a series of simplified digitalis-like compounds acting on Na+,K+-ATPase

Among the cardiotonics (agents against congestive heart failure), the most important group is of the digitalis cardiac glycosides, but since these compounds suffer from a low therapeutic index, attention has been paid to investigating safer cardiotonic agents through the inhibition of Na+,K+-ATPase, the mechanism by which the digitalis cardiac glycosides elicit their action. Recently, a series of perhydroindenes were studied for their Na+,K+-ATPase inhibition activity. We report here a QSAR study on them to investigate the physicochemical and structural properties of the molecules that govern their activity in order to rationalize the structural modification to have more potent drugs. A multiple regression analysis reveals a significant correlation between the Na+,K+-ATPase inhibition activity of the compounds and Kier’s first order valence molecular connectivity index of their R5-substituents and some indicator parameters, suggesting that the R5-substituents of the compounds containing atoms with low valence and high saturation and the R1-substituents having =N−O− moiety will be conducive to the activity.

Levosimendan: uma nova alternativa no menejo da insuficiência cardíaca em terapia intensiva / Levosimedan: a new alternative for managing cardiac insufficiency in intensive care

Introdução: O usuo de levosimendan em pacientes criticamente enfermos e, principalmente, nos que se apresentam com pressão arterial média inferior a 60mmHG, ainda não teve a sua eficácia e a sua segurança estabelecidas.Objetivos: avaliar a resposta do levosimendan em cardiopatas graves já em uso de dobutamina e noradrenalina.Métodos: foram avaliados de forma propspectiva 37 pacientes internados em ambiente de terapia intensiva geral e cardiológica, sendo 51,3 por cento (n=19) do sexo masculino e 48,7 por cento (n=18) do sexo feminino. A média de idade doi de 65,3 anos, variando entre 49 e 84 anos, todos em classe funcional IV, segundo a classificação da NYHA, e dependentes da infusão venosa contínua de dobutamina com doses Superiores a 5ug/kg/min, sendo que 15 deles (40,5 por cento) estavam dependentes também de noradrenalina (dose acima de 0,05ug/kg/min)...

Triagem fitoquímica preliminar de tetrapterys multiglandulosa A. Juss. (Malpighiaceae) / Preliminary phytochemical screening of tetrapterys multiglandulosa A. Juss. (Malpighiaceae)

Este trabalho foi desenvolvido com o objetivo de identificar os princípios tóxicos da tetrapterys multigalndulosa A. Juss. Realizou-se triagem fitoquímica nas folhas (brotos e maduras) frescas, através de marcha analítica clássica e Cromatografia em Camada Delgada (CCD) pesquisando-se os seguintes princípios ativos: heterosídeos antrasênicos, saponínicos, flavônicos, cardiotônicos, taninos (hidrolisáveis e condensados), alcalóides (terciários e quaternários), composto esteróides e cumarínicos. Os resultados obtidos mostraram na folha jovem e madura, presença de heterosídeos flavônicos e esteróides. Taninos condensados e alcalóides quaternários foram encontrados somente na folha madura.

Synthesis of novel 4, 5-dihydropyridazin - 3 [2H] - one derivatives with benzoxazine and benzoxazole heterocycles at the 6-position as cardiotonic agents

A series of pyridazinone derivatives carrying benzoheterocycles, such as benzoxazole and benzoxazine, was synthesized and tested as inhibitors of cAMP phosphodiesterase enzyme [PDE]. The most promising compound in this series was 6-[2,4-dioxo-3,4-dihydro- l,3[2H]-benzoxazin-6-yl]-4,5 dihydropyridazin-3[2H]-one [3], which showed potent inhibiting activity on cAMP PDE and was ten times more potent than milrinone [a commercially available cardiotonic agent]

Synthesis of 6- [4- [substituted - amino] phenyl] - 4,5 -dihydropyridazin-3 [H] ones as potential positive inotropic agents

A series of 6-[4-[substituted-amino]phenyl] pyridazinones and related compounds were synthesized and evaluated as inhibitors of cardiac cyclic AMP phosphodiesterase. Compounds 2c, 2d, 2h showed potent inhibitory activity and were found more potent than milrinone