Development of synthetic organic chemistry methods to selectively transform steroid derivatives to access known metabolites and impurities, and novel drug-like structures

开发合成有机化学方法来选择性地转化类固醇衍生物以获得已知的代谢物和杂质以及新颖的药物样结构

• 批准号: 543543-2019
• 负责人: Adler, Marc
• 金额: $ 1.82万
• 依托单位: Ryerson University
• 依托单位国家: 加拿大
• 项目类别: Engage Grants Program
• 财政年份: 2019
• 资助国家: 加拿大
• 起止时间: 2019-01-01 至 2020-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=680516
• 关键词: Development; synthetic; organic; chemistry; methods

Dalton Pharma Services is a leading manufacturer of pharmaceutical products and provider of analytical services to the pharmaceutical and biotechnological industries. Dalton is particularly interested in steroid compounds because of the high demand for standards, metabolites, and impurities from customers for their research and development needs. They are currently facing a technological problem in efficiently making certain classes of steroid compounds.This collaborative project between Dalton Pharma and Prof. Marc J. Adler's lab at Ryerson University seeks to discover new chemical methods to selectively transform molecules of biological interest, including steroids. The specific goal is to develop highly specific ways to reduce ketones to secondary alcohols, allowing for the differentiation of two ketones in a steroid molecules with similar reactivity profiles; this selective reactivity is vital to make particular subsets of steroid analogues. Currently differentiation requires a multi-step synthetic process, resulting in significant chemical waste, expenditure of time, and decrease in product yield. We aim to directly differentiate the two functional groups for chemical transformation, thus providing a more efficient and greener path to the desired products. Such products include known metabolites of and impurities in drugs. This method will also provide ready access to new bioactive molecules to be evaluated as potential probes or therapeutics. The collaborative project will train two Master's students who will develop innovative and industrially relevant chemical synthesis methods in close collaboration with Dalton Pharma scientists.

道尔顿制药服务公司是一家领先的制药产品制造商，并为制药和生物技术行业提供分析服务。道尔顿对类固醇化合物特别感兴趣，因为客户对标准品、代谢物和杂质的需求很高，以满足其研发需求。他们目前正面临着一个技术问题，有效地使某些类别的类固醇化合物。这个合作项目之间的道尔顿制药公司和马克J.阿德勒教授的实验室在瑞尔森大学寻求发现新的化学方法来选择性地转化生物感兴趣的分子，包括类固醇。具体目标是开发高度特异性的方法来将酮还原为仲醇，允许在具有相似反应性特征的类固醇分子中区分两种酮;这种选择性反应性对于制备类固醇类似物的特定子集至关重要。目前的分化需要多步合成过程，导致显著的化学浪费、时间消耗和产物产率降低。我们的目标是直接区分这两个官能团进行化学转化，从而为所需产品提供更高效、更绿色的途径。这些产物包括药物中已知的代谢产物和杂质。该方法还将提供容易获得的新的生物活性分子，以作为潜在的探针或治疗剂进行评估。该合作项目将培养两名硕士生，他们将与道尔顿制药公司的科学家密切合作，开发创新和工业相关的化学合成方法。