ISOQUINOLINE BETA3-AR AGONISTS AS ANTIOBESITY AGENTS

超过三分之一的美国人超重(肥胖)，这一点很重要 找出治疗这种疾病的新疗法。一批 方法包括流质饮食，卡路里计算，脂肪计算， 商业减肥计划，以及药物的使用。20世纪60年代的S 1970年S的安非他命是首选药物，但它们引起了 很多问题，包括上瘾。在20世纪90年代的S和芬氟拉明 芬太明是用来降低食欲的。然而，有一些 三种药物的使用及其对5-羟色胺影响的主要问题 中锋。这项提议的目标是设计、合成、 表征和测试四氢异喹啉类似物的能力 通过选择性激活β-肾上腺素能受体分解脂肪。 米勒博士将在密歇根大学合成设计的分子 田纳西州。MDI的珀塞尔博士将与我们合作，使用QSAR CoMFA程序优化Beta3-激活结构 肾上腺素能受体和密西西比大学的费勒博士， 将测试化合物对三种物质的结合和激活 人类β-肾上腺素能受体的亚型。选择性Beta3- 肾上腺素能药物将用于治疗肥胖和非肥胖症 胰岛素依赖型糖尿病。

More than 1/3 of Americans are overweight (obese), and it is important to identify new therapeutic treatments for this condition. A number of approached include liquid diets, calorie counting, fat counting, commercial weight loss programs, and the use of drugs. In the 1960's and 1970's amphetamines were the drug of choice, but they caused many problems including addiction. In the 1990's fenfluramine and phentemine are used to reduce the appetite. However, there are some major concerns about the use of thee drugs and the effects on serotonin centers. The objective of this proposal is to design, synthesize, characterize, and test tetrahydroisoquinline analogs for their ability to break down fat through he selective activation of betas-adrenoceptors. Dr. Miller will synthesize the designed molecules at The University of Tennessee. Dr. Purcell from MDI will work with us using the QSAR CoMFA program to optimize the structures for activation of beta3- adrenergic receptors and Dr. Feller, at The University of Mississippi, will test the compounds for the binding and activation of the three subtypes of human beta-adrenergic receptors. Selective beta3- adrenergic drugs will be useful for the treatment of obesity and non insulin dependent diabetes mellitus.