Abstract:The combination of antagonism at histamine H 3 receptor and the stimulation of insulin secretion have been proposed as an approach to new dual therapeutic agents for the treatment of type 2 diabetes mellitus associated with obesity. We have designed and synthesized a new series of non-imidazole derivatives, based on a basic amine ring connected through an alkyl spacer of variable length to a phenoxysulfonylurea moiety. These compounds were initially evaluated for histamine H 3 receptor binding affinities, suggesting that a propoxy chain linker between the amine and the core ring could be essential for optimal binding affinity. Compound 56, 1-(naphthalen-1-yl)-3-[(p-(3-pyrrolidin-1-ylpropoxy)benzene)]sulfonylurea exhibited the best H 3 antagonism affinity. However, since all these derivatives failed to block K ATP channels, the link of these two related moieties should not be considered a good pharmacophore for obtaining new dual H 3 antagonists with insulinotropic activity, suggesting the necessity to propose a new chemical hybrid prototype.
Obesity is a chronic disease characterized by the accumulation of excess adipose tissue associated with an increased risk of multiple morbidities and mortality. At the present time, only three drugs have been approved by the Food and Drug Administration (FDA) for the treatment of obesity. Agonists and antagonists of some of the substances implicated in the regulation of energy homeostasis represent opportunities for anti-obesity drug development. The most promising targets are alpha-melanocyte stimulating hormone (alpha-MSH) receptors, cannabinoid receptors, the 5-hydroxytryptamine (5-HT) receptors and melanin-concentrating hormone (MCH) receptors. MCH receptors could be major potential targets for the treatment of obesity. Many pharmaceutical companies have described MCH-R1 antagonists that have appeared over the past year. Recently, two compounds went into phase I clinical trials that evaluate MCH receptor antagonists as a new perspective for the pharmacologic treatment of obesity. In this review, structure-activity relationships (SAR) in the development of MCH-R1 antagonists are provided.
Intense pressure on water resources has led to efforts to reuse reclaimed processing wastewater in the food industry. There are tight rules for water quality, but efficient separation technologies such as reverse osmosis possess good possibilities for water reuse. This study developed a membrane-based reuse water concept for wastewater from the candy industry emphasizing the pre-treatment stage in the concept to reduce fouling. The wastewater contained suspended solids, sugar compounds and the ingredients for candy gelation, which had a tendency to foul membranes, making pre-treatment essential for successful concept. Cross-rotational ultrafiltration, which featured enhanced fouling prevention for membranes, functioned well for the removal of challenging substances. Conventional filtration technologies were impractical due to a low flux, even when the viscosity of the wastewater was reduced using surfactants. The wastewater had a high chemical oxygen demand, meaning that there were a strong fouling potential for reverse osmosis membranes, but also high osmotic pressure. A spiral wound reverse osmosis functioned well when the wastewater was pre-treated, and it produced good quality water with respect to all the other studied parameters except the chemical oxygen demand. However, chemical oxygen demand rejection was 99% since the concentration in the wastewater was originally very high.
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