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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：
10389320
负责人：
Corey Stephenson
金额：
$ 8.67万
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

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

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Advancements in Visible-Light-Enabled Radical C(sp)2-H Alkylation of (Hetero)arenes.

DOI：
10.1055/s-0037-1611658
发表时间：
2019-03
期刊：
Synthesis
影响因子：
0
作者：
通讯作者：

Aryl Transfer Strategies Mediated by Photoinduced Electron Transfer.

DOI：
10.1021/acs.chemrev.1c00388
发表时间：
2022-01-26
期刊：
CHEMICAL REVIEWS
影响因子：
62.1
作者：
Allen, Anthony R.;Noten, Efrey A.;Stephenson, Corey R. J.
通讯作者：
Stephenson, Corey R. J.

Photochemical Formal (4 + 2)-Cycloaddition of Imine-Substituted Bicyclo[1.1.1]pentanes and Alkenes.

DOI：
10.1021/jacs.1c10541
发表时间：
2021-12-22
期刊：
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
影响因子：
15
作者：
Harmata, Alexander S.;Spiller, Taylor E.;Sowden, Madison J.;Stephenson, Corey R. J.
通讯作者：
Stephenson, Corey R. J.

Development of an automated screen for Kv7.2 potassium channels and discovery of a new agonist chemotype.

DOI：
10.1016/j.bmcl.2022.128841
发表时间：
2022-09-01
期刊：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
影响因子：
2.7
作者：
Hernandez, Ciria C.;Tarfa, Rahilla A.;Limcaoco, Jose Miguel I.;Liu, Ruiting;Mondal, Pravat;Hill, Clare;Duncan, R. Keith;Tzounopoulos, Thanos;Stephenson, Corey R. J.;O'Meara, Matthew J.;Wipf, Peter
通讯作者：
Wipf, Peter