Medicinal Chemistry and Pharmacokinetics Core

药物化学和药代动力学核心

• 批准号: 9070624
• 负责人: JAMES R FUCHS
• 金额: $ 13.13万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-14 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9070624
• 关键词: Antineoplastic Agents; Binding; Biological; Biological Assay; Blood Cells; Cells; Chicago; Comprehensive Cancer Center; Dose; Drug Kinetics; Effectiveness; Enzymes; Evaluation; Fiber; Formulation; Goals; Illinois; In Vitro; Instruction; Investigation; Lead; Modification; Mus; Natural Products; North Carolina; Ohio; Pharmaceutical Chemistry; Pharmaceutical Preparations; Plants; Plasma; Preparation; Property; Proteins; Resource Sharing; Services; Solubility; Structure-Activity Relationship; Time; Universities; Work; chemical synthesis; improved; in vivo; metabolic profile; novel anticancer drug; programs; scaffold; scale up; silvestrol

The following are the objectives of Core B at The Ohio State University (OSU): (1) Synthesize sufficient quantities of selected natural products for more extensive biological evaluation, (2) Explore structure-activity relationships (SAR) and optimize pharmacological properties of highly promising agents through systematic modification of the natural product scaffold. All new compounds synthesized in these studies will be submitted for the bioassays proposed in Projects 1 and 3 and Core A, (3) Support the structural assignment of isolated natural products through chemical synthesis and/or semi-synthetic derivatization, as necessary, (4) Develop sensitive, selective, accurate and precise assays to quantify lead compounds in in vitro and in vivo biological matrices, (5) Characterize solubility, stability and metabolic profiles of lead compounds in dosing formulations and in vitro cell and enzyme preparations to support optimal formulation and derivatization, as necessary, and (6) Produce pilot plasma concentration-time profiles and determine protein and blood cell binding in mice for early estimation of pharmacokinetic properties for select compounds prior to entry into hollow fiber assays. RELEVANCE (See instructions): The primary goal of Core B is to support the discovery, characterization and optimization of novel anticancer agents through the synthesis, structural modification, and evaluation of pharmacokinetic properties of lead compounds discovered in Projects 1-3 that demonstrate promising biological activity.

以下是俄亥俄州立大学（OSU）的Core B的目标：（1）合成足够的 选定的天然产物数量以进行更广泛的生物学评估，（2）探索结构活性 关系（SAR）并通过系统的 自然产品支架的修改。这些研究中合成的所有新化合物将是 提交项目1和3和核心A中提议的生物测定 通过化学合成和/或半合成衍生化分配孤立的天然产物 （4）开发敏感，选择性，准确和精确的测定，以量化铅化合物 体内和体内生物学基质，（5）表征铅的溶解度，稳定性和代谢谱 剂量配方中的化合物以及体外细胞和酶制剂以支持最佳配方 必要时和衍生化，（6）产生试点血浆浓度时间曲线并确定 小鼠中的蛋白质和血细胞结合，以早期估算精选的药代动力学特性 进入进入空心纤维测定之前的化合物。 相关性（请参阅说明）： 核B的主要目标是支持新型抗癌的发现，表征和优化 通过铅的药代动力学特性的合成，结构修饰和评估代理 在项目1-3中发现的化合物证明了有希望的生物学活性。