A new class of non-opioid analgesics for use in chronic pain management

 描述(申请人提供)：急性和慢性疼痛给社会带来了巨大的负担，不仅因为相关的人类痛苦，而且还因为医疗费用、生产力损失和伤残抚恤金，据估计，仅在美国每年就高达6500亿美元。目前对疼痛的治疗受到疗效有限和急性或长期副作用的阻碍。对乙酰氨基酚是一种重要的止痛药物；然而，过量服药(这很常见)会导致肝脏损伤、随后的肝功能衰竭，甚至死亡。一种安全的无肝毒性药物，与对乙酰氨基酚的疗效相当或更好，将是治疗疼痛的开创性新产品。Kalyra制药公司利用我们专有的生物等位基因工具箱，合成了一些结构相关的对乙酰氨基酚类似物，并发现了新的高效止痛化合物，这些化合物不会形成有毒的代谢物。随着概念的证明，这些类似物的进一步开发是这项直接到第二阶段提案的主题，具体目标概述如下：第二阶段：疼痛新疗法的非临床开发目标1.进一步的疗效表征和活体药理学目标2.安非他明、额外的药理学和初步毒理学目标3.药物动力学研究以确认安全目标的第二种选择4.非临床毒理学研究支持提交IND在完成本提案中概述的IND使能研究之后，我们预计将向FDA提交IND，以开始开发一种新的、安全的、有效且不会上瘾的疼痛管理新疗法。

 DESCRIPTION (provided by applicant): Acute and chronic pain imposes a tremendous burden on society, not only because of the associated human suffering, but also the cost of medical treatment, loss of productivity and disability payments, which has been estimated to be up to $650 billion per year in the USA alone. Current treatments for pain are hampered by limited efficacy and acute or long-term side effects. Acetaminophen is an important drug in the management of pain; however, overdose (which is quite common) can lead to liver damage, subsequent liver failure, and even death. A safe non-liver toxic drug, with equal or improved efficacy compared to acetaminophen, would be a ground breaking new product for the treatment of pain. Kalyra Pharmaceuticals has synthesized a number of structurally related acetaminophen analogs, utilizing our toolbox of proprietary bioisosteres, and discovered new highly potent analgesic compounds that do not form a toxic metabolite. With proof of concept in hand, further development of these analogues is the subject of this direct to Phase II proposal, via the Specific Aims outlined below: Phase II: Non-Clinical Development of a New Treatment for Pain Aim 1. Further Characterization of Efficacy and In Vivo Pharmacology Aim 2. ADMET, Additional Pharmacology and Preliminary Toxicology Aim 3. Pharmacokinetic Studies to Confirm Second Species Selection for Safety Aim 4. Non-Clinical Toxicology Studies in Support of Filing of an IND After completion of the IND-enabling studies outlined in this proposal, we anticipate the filing of an IND with the FDA to begin human clinical trials for the development of a novel, safe, effective and non-addictive new treatment for the management of pain.