申请人:Murphy Michael A.
公开号:US20140057877A1
公开(公告)日:2014-02-27
This invention relates to a process of synthesis and composition of open chain (ring), closed ring, linear branched and or substituted polyamines, polyamine derived tyrosine phosphatase inhibitors and PPAR partial agonists/partial antagonists via a series of substitution reactions and optimizing the bioavailability and biological activities of the compounds. Polyamines prevent the toxicity of neurotoxins and diabetogenic toxins including paraquat, methyphenyl pyridine radical, rotenone, diazoxide, streptozotocin and alloxan. These polyamines can be utilized to treat neurological, cardiovascular, endocrine acquired and inherited mitochondrial DNA damage diseases and other disorders in mammalian subjects, and more specifically to the therapy of Parkinson's disease, Alzheimer's disease, Lou Gehrig's disease, Binswanger's disease, Olivopontine Cerebellar Degeneration, Lewy Body disease, Diabetes, Stroke, Atherosclerosis, Myocardial Ischemia, Cardiomyopathy, Nephropathy, Ischemia, Glaucoma, Presbycussis, Cancer, Osteoporosis, Rheumatoid Arthritis, Inflammatory Bowel Disease, Multiple Sclerosis and as Antidotes to Toxin Exposure.
本发明涉及一种通过一系列取代反应合成和组成开链(环)、闭合环、线性支链和/或取代的多胺、多胺衍生的酪氨酸磷酸酶抑制剂和PPAR部分激动剂/部分拮抗剂的过程,并优化化合物的生物利用度和生物活性。多胺可以预防神经毒素和糖尿病毒素(包括百草枯、甲基苯基吡啶自由基、罗滕酮、重组胰岛素和阿洛酮)的毒性。这些多胺可用于治疗哺乳动物主体的神经、心血管、内分泌获得性和遗传性线粒体DNA损伤疾病和其他疾病,更具体地说是治疗帕金森病、阿尔茨海默病、路易·格里格病、宾斯旺格病、橄榄桥小脑变性、Lewy体病、糖尿病、中风、动脉粥样硬化、心肌缺血、心肌病、肾病、缺血、青光眼、老年性耳聋、癌症、骨质疏松症、类风湿性关节炎、炎症性肠病、多发性硬化症以及作为毒素暴露的解毒剂。