Medicinal Chemistry and Pharmacokinetics Core

药物化学和药代动力学核心

• 批准号: 8608731
• 负责人: JAMES R FUCHS
• 金额: $ 13.55万
• 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 2019-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8608731
• 关键词: Antineoplastic Agents; Binding; Biological; Biological Assay; Biological Factors; Blood Cells; Cells; Chicago; Comprehensive Cancer Center; Dose; Drug Formulations; Drug Kinetics; Effectiveness; Enzymes; Evaluation; Fiber; Goals; Illinois; In Vitro; Instruction; Investigation; Lead; Metabolic; Modification; Mus; 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; novel; 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) 核心 B 的目标： (1) 综合充分 大量选定的天然产物以进行更广泛的生物学评价，（2）探索结构-活性 关系（SAR）并通过系统优化高度有前途的药物的药理学特性 天然产物支架的修饰。这些研究中合成的所有新化合物都将 提交项目 1 和 3 以及核心 A 中提议的生物测定，(3) 支持结构 通过化学合成和/或半合成衍生化分离的天然产物的分配，如 必要时，(4) 开发灵敏、选择性、准确和精确的分析方法来量化中的先导化合物 体外和体内生物基质，(5) 表征铅的溶解度、稳定性和代谢特征 剂量配方以及体外细胞和酶制剂中的化合物，以支持最佳配方 必要时进行衍生化，以及 (6) 生成试验血浆浓度-时间曲线并确定 小鼠中的蛋白质和血细胞结合，用于早期估计选择的药代动力学特性 化合物在进入中空纤维测定之前。 相关性（参见说明）： Core B 的主要目标是支持新型抗癌药物的发现、表征和优化 通过铅的合成、结构修饰和药代动力学特性评价来治疗药物 项目 1-3 中发现的化合物显示出有前景的生物活性。