Medicinal Chemistry and Pharmacokinetics Core

以下是州立大学俄亥俄州（OSU）核心B的目标：（1）合成足够的 大量的天然产物进行更广泛的生物学评价，（2）探索结构-活性 关系（SAR），并通过系统的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。在这些研究中合成的所有新化合物都将是 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/或半合成衍生化来分配分离的天然产物，如 （4）开发灵敏、选择性、准确和精确的测定方法，以定量测定体内的先导化合物。 体外和体内生物基质，（5）表征铅的溶解性、稳定性和代谢特征 给药制剂和体外细胞和酶制剂中的化合物，以支持最佳制剂 和衍生化，如有必要，和（6）产生试点血浆浓度-时间曲线，并确定 小鼠中蛋白质和血细胞的结合，用于早期估计选择的 在进入中空纤维测定之前，对化合物进行分析。 相关性（参见说明）： 核心B的主要目标是支持新型抗癌药物的发现、表征和优化。 通过合成、结构修饰和评价铅的药代动力学特性来研究药物 在项目1-3中发现的化合物显示出有希望的生物活性。

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.