Novel THC/Anandamide Hybrids as Appetite Suppressants

新型 THC/Anandamide 混合物作为食欲抑制剂

• 批准号: 7121505
• 负责人: Anuradha Mahadevan
• 金额: $ 24.44万
• 依托单位: ORGANIX, INC.
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-15 至 2009-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7121505
• 关键词: analog; anandamide; anorexic agent; appetite; cannabinoid receptor; drug design /synthesis /production; inhibitor /antagonist; laboratory mouse; obesity

Obesity has reached epidemic proportions and in a year about 300,000 people die of obesity-related diseases. Annual medical spending due to obesity and overweight is about $117 billion. There is an urgent need to discover effective drugs to treat this disease since existing drugs have modest efficacy and significant side effects. A potentially promising target for anti-obesity drugs is the cannabinoid (CB1) receptor. In Phase I of this proposal our focus will be on the structural optimization of our novel THC/anandamide template to discover one or more CB1 receptor antagonists. In order to distinguish between agonist and antagonist activity, analogs that bind effectively to the CB1 receptor, will be evaluated for their ability to stimulate [35S]GTPgS binding. Our specific objective is to discover and select the best analogs in this series that manifest in vivo activity in a mouse model for appetite suppression. If the above objective is accomplished in Phase I, we will have a drug candidate for further development in Phase II. The long-term objective of this proposal is to develop a novel anti-obesity drug that is both safe and effective.

肥胖症已经达到了流行病的比例，并在一年中大约有30万人死于与肥胖有关的疾病。由于肥胖和超重而导致的年度医疗支出约为1,170亿美元。由于现有药物具有适度的功效和重大副作用，因此迫切需要发现有效的药物来治疗该疾病。抗肥胖药物的潜在有希望的靶标是大麻素（CB1）受体。在该提案的第一阶段，我们的重点将放在我们新型THC/anandamide模板的结构优化上，以发现一个或多个CB1受体拮抗剂。为了区分激动剂和拮抗剂活性，将评估与CB1受体有效结合的类似物，以评估其刺激[35S] GTPG结合的能力。我们的具体目标是发现并选择本系列中最好的类似物，这些类似物在小鼠模型中表现出体内活性以抑制食欲。如果以上 目标是在第一阶段实现的，我们将有一个在II期进一步发展的药物。该提议的长期目标是开发一种既安全有效又有效的新型抗肥胖药物。