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Photochemical synthesis of bioactive molecules

生物活性分子的光化学合成

基本信息

批准号：
10252005
负责人：
Corey Stephenson
金额：
$ 41.49万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-20 至 2022-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10252005
关键词：
Acrylamides Address Agonist Amines Aniline Antineoplastic Agents Antiparasitic Agents Area Biological Biological Assay Cations Cell-Mediated Cytolysis Cells Chemicals Clinic Conscious Creativeness Cyclodextrins Development Discipline ERBB2 gene Electrophysiology (science)Engineering Ensure Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Evaluation Family Generations Goals Health Hearing problem Hepatotoxicity Human Individual Investigation Investments Ion Channel Libraries Malignant Neoplasms Mediating Metabolic Metabolism Methods Modernization Molecular Niemann-Pick Diseases Nitrogen Oncology Patients Pharmaceutical Preparations Phosphotransferases Photochemistry Positioning Attribute Preparation Prevention Process Property Quinazolines Reaction Reagent Research Risk Factors Role Science Site Structure Therapeutic Intervention Tinnitus Toxic effect Translating Ursidae Family Variant Visible Radiation analog antimicrobial base cancer therapy chemical reaction chemical synthesis cycloaddition design drug discovery functional group high risk immunogenicity innovation interest lapatinib malignant breast neoplasm neglected tropical diseases novel novel therapeutics ototoxicity patch clamp scaffold therapeutic development wasting

项目摘要

PROJECT SUMMARY The overarching theme of this proposal is the development and application of new and enabling photocatalytic methods for the preparation of compounds capable of mimicking the structure of aniline motifs commonly found in drug molecules. These approaches provide strategy-level advantages in their respective synthetic applications due to broad functional group compatibility, mild reaction conditions, scalability, and operational simplicity while simultaneously incorporating metabolism-based design criteria early in the drug discovery process. New methods using visible light, a non-toxic 'reagent' that does not generate chemical waste, are attractive strategies for chemical synthesis circumventing the reliance upon expensive and synthetically challenging starting material preparation, further enabling synthesis in an environmentally conscious fashion. The major goals of this proposal leverage strain-releasing ring-opening reactions for the preparation of previously inaccessible motifs and the demonstration of their utility as replacements of metabolically-labile aniline functionality in drug discovery. Specifically we will leverage these chemical findings to address modern challenges in therapeutic development, namely: 1) novel KCNQ agonists for unmet needs in hearing disorders (i.e. tinnitus; cyclodextrin-induced ototoxicity); and 2) metabolically-inert analogs of lapatinib which will represent new leads in cancer therapy and antimicrobial research while also serving as biological probes for studying the immunogenicity of hepatotoxic drugs.. These goals translate creativity in reaction science into immediately-impactful and multi-faceted applications in drug discovery and are intended to demonstrate the broad-reaching influence that can arise from investment in synthetic innovation.

项目总结