DEVELOPMENT OF ANALGESICS WITH FEWER SIDE EFFECTS

描述（改编自申请人摘要）： 止痛药，如对乙酰氨基酚和非甾体抗炎药 非甾体抗炎药（NSAID）已用于治疗疼痛和/或发热多年。 这种双重作用有时是禁忌的。在许多情况下，疼痛需要 在不掩盖发烧症状的情况下得到控制（例如，术后 期间）。这些药物也会引起肝毒性，特别是在 摄入大剂量或长期使用较小剂量（特别是当肝脏 功能已经受损），可能导致死亡。因此有 需要具有更大药理效力的新的更具选择性的化合物 肝毒、肾毒、解热作用小。圣查尔斯群岛 探索一系列新的和专有的对乙酰氨基酚衍生物。在 初步研究表明，其中一种化合物具有高镇痛作用， 无解热活性和肝毒性。在此SBIR中 项目我们建议进一步表征这些初始化合物， 探索系列优化其物理、化学和生物 特性.第一阶段的可行性实验将确定主要候选人 我们将在第二阶段进一步测试和开发的药物，用于治疗 术后疼痛，肺炎相关疼痛，慢性疼痛，幻肢 疼痛，以及对乙酰氨基酚禁忌的镇痛治疗。 拟定商业应用：不可用

DESCRIPTION (ADAPTED FROM APPLICANT'S ABSTRACT): Analgesics such as acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) have been used for many years for the treatment of pain and/or fever. This dual action is sometimes contraindicated. In many instances pain needs to be controlled without masking the symptomatic fever (e.g., the postoperative period). These drugs can also cause hepatotoxicity, particularly after ingestion of large doses or chronic use of smaller doses (especially when liver function have has been compromised) that can lead to death. Therefore, there is a need for new more selective compounds with greater pharmacological potency and little hepatotoxic, nephrotoxic, or antipyretic effects. St Charles is exploring a series of new and proprietary derivatives of acetaminophen. In preliminary studies, one of these compounds demonstrated high analgesic activity free from antipyretic activity and hepatotoxicity. In this SBIR project we propose to further characterize these initial compounds and to explore the series to optimize their physical, chemical and biological properties. The feasibility experiments in phase I will identify lead candidate drug(s) that we will further test and develop in phase II for the treatment of postoperative pain, pain associated with pneumonia, chronic pain, phantom limb pain, and for analgesic treatment where acetaminophen is contraindicated. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE