RESUMO
Lysophosphatidic acid (LPA) is a bioactive lipid mediator that elicits a number of biological functions, including smooth muscle contraction, cell motility, proliferation, and morphological change. LPA is endogenously produced by autotaxin (ATX) from extracellular lysophosphatidylcholine (LPC) in plasma. Herein, we report our medicinal chemistry effort to identify a novel and highly potent ATX inhibitor, ONO-8430506 (20), with good oral availability. To enhance the enzymatic ATX inhibitory activity, we designed several compounds by structurally comparing our hit compound with the endogenous ligand LPC. Further optimization to improve the pharmacokinetic profile and enhance the ATX inhibitory activity in human plasma resulted in the identification of ONO-8430506 (20), which enhanced the antitumor effect of paclitaxel in a breast cancer model.
RESUMO
A novel immobilization of an enzyme with a hydrophilic polymer support in organic solvents has been developed utilizing the "polymer-incarcerated (PI) method", which has been used to immobilize metal catalysts; the kinetic resolution of secondary alcohols was found to proceed more smoothly using immobilized lipases (CALB) than free lipases.
Assuntos
Álcoois/química , Enzimas Imobilizadas/química , Lipase/química , Polímeros/química , Catálise , Proteínas Fúngicas , Especificidade por Substrato , Água/químicaAssuntos
Líquidos Iônicos/química , Escândio/química , Dióxido de Silício/química , Álcoois/síntese química , Álcoois/química , Aldeídos/química , Catálise , Cetonas/síntese química , Cetonas/química , Estrutura Molecular , Compostos de Organossilício/síntese química , Compostos de Organossilício/química , Água/químicaRESUMO
"Miniaturization" is one of the most important aspects in today's technology. Organic chemistry is no exception. The search for highly effective, controllable, environmentally friendly methods for preparing products is of prime importance. The development of multiphase organic reactions in microchannel reactors has gained significant importance in recent years to allow novel reactivity, and has led to many fruitful results that are not attainable in conventional reactors. This Focus Review aims to shed light on how effectively multiphase organic reactions can be conducted with microchannel reactors by providing examples of recent remarkable studies, which have been grouped on the basis of the phases involved.
Assuntos
Compostos Orgânicos/síntese química , Catálise , Miniaturização , Propriedades de SuperfícieRESUMO
We have developed an effective microfluidic system for hydrogenation reactions in scCO(2); the reactions proceeded very rapidly (within 1 second), by making the best use of scCO(2) and utilizing the large specific interfacial area of the microchannel reactor, and high reaction productivity was attained in each channel.
Assuntos
Dióxido de Carbono/química , Microfluídica/instrumentação , Catálise , Cromatografia com Fluido Supercrítico , Hidrogenação , Microfluídica/métodos , Pressão , Sensibilidade e Especificidade , Solventes/química , Propriedades de SuperfícieRESUMO
We have developed an efficient system for triphase reactions using a microchannel reactor. Using this system, we conducted hydrogenation reactions that proceeded smoothly to afford the desired products quantitatively within 2 minutes for a variety of substrates. The system could also be applied to deprotection reactions. We could achieve an effective interaction between hydrogen, substrates, and a palladium catalyst using extremely large interfacial areas and the short path required for molecular diffusion in the very narrow channel space. This concept could be extended to other multiphase reactions that use gas-phase reagents such as oxygen and carbon dioxide.