Innovative Medicinal Chemistry Core

创新药物化学核心

• 批准号: 8940569
• 负责人: Peter Wipf
• 金额: $ 39.78万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8940569
• 关键词: Address; Apoptosis; BODIPY; Biological; Biomedical Research; Cardiolipins; Cessation of life; Chemicals; Communities; Detection; Drug Formulations; Evaluation; Event; Exposure to; Fatty Acids; Generations; Goals; Grant; Health; Heart; High Pressure Liquid Chromatography; Homologous Gene; Imidazole; Isotope Labeling; Label; Lead; Mission; Modification; Necrosis; New Agents; Pathology; Pathway interactions; Personal Satisfaction; Pharmaceutical Chemistry; Pharmaceutical Preparations; Population; Procedures; Property; Radiation; Radiation-Protective Agents; Research Infrastructure; Risk; Signal Transduction; Structure; Structure-Activity Relationship; Therapeutic; Tissues; Uncertainty; Universities; Validation; Variant; Work; abstracting; analog; base; chemical synthesis; cost; design; drug development; fluorophore; follow-up; in vivo; innovation; lipid mediator; material transfer agreement; novel; programs; radiation adverse effect; radiation-induced injury; scale up; small molecule; therapeutic development; tool

Abstract: Small organic molecules also continue to be of great utility as biological tools for the identification and characterization of new targets and inhibitory or stimulatory mechanisms, as well as for low-cost large-scale therapeutic applications. Our Core provides unique small molecule synthesis and analysis capabilities based on innovative medicinal chemistry and analytical procedures to the CMCR, and we have a successful track record for working synergistically in developing novel tool compounds and therapeutic candidates for radiation mitigation. Our specific aims are: 1. To synthesize labeled (fluorescent-and isotope-labeled) variants of (a) necrostatin-1, (b) MMS350, (c) varespladib, and (d) R-BEL for Projects 1, 3 and 4 as well as Core H. 2. To supply Project 1 and Core G with scaled-up quantities of BODIPY-JP4-039 and MMS-350. 3. To supply Project 2 with lipid mediators, including homologs of cardiolipins. 4. To supply Projects 1, 2 and 3 with (a) imidazole fatty acid derivatives, (b) MitoEbselen-2, and (c) hepoxillin-A3 and analogs thereof; and 5. To perform EPR and HPLC analyses with either direct electrochemical detection of the analytes or, following tissue extraction, FL detection after derivatization with fluorophores.

翻译后摘要：小有机分子也继续作为生物工具的巨大效用 用于新靶点以及抑制性或刺激性的识别和表征 机制，以及低成本的大规模治疗应用。我们的核心 提供独特的小分子合成和分析能力， 药物化学和分析程序的CMCR，我们有一个成功的 在开发新型工具化合物方面的协同工作记录， 用于减轻辐射的治疗候选物。我们的具体目标是：1.合成 （a）坏死抑素-1，（B）MMS 350，（c）的标记（荧光和同位素标记）变体 伐瑞拉迪，和（d）R-BEL用于项目1、3和4以及核心H。2.提供 项目1和核心G，BODIPY-JP 4 -039和MMS-350的数量按比例增加。3.到 为项目2提供脂质介质，包括心磷脂同系物。4.提供 项目1、2和3：（a）咪唑脂肪酸衍生物，（B）MitoEbselen-2，和（c） hepoxillin-A3及其类似物;和5.进行EPR和HPLC分析， 或者直接电化学检测分析物，或者在组织提取后，FL 用荧光团衍生化后检测。