在新的14-基-6-oxomorphinans的enantioselective合成
Jonathan C Moore1,2, Louis Modell3, Jacqueline R Glenn4,5
1The GlaxoSmithKline Carbon Neutral Laboratories for Sustainable Chemistry, University of Nottingham, Jubilee Campus, Triumph Road, Nottingham, NG7 2TU, UK. hon.lam@nottingham.ac.uk.
开发了一种合成14-基-6-oxomorphinans的新方法. 这一途径成功地产生了4,5-desoxynaltrexone和4,5-desoxynaloxone,随后评估了它们的阿片类受体活性.
科学领域:
- 有机化学 有机化学
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
背景情况:
- 14-基-6-oxomorphinans 在阿片类受体调节中是关键的药理.
- 开发这些化合物的高效合成路径对于药物发现至关重要.
- 现有的方法可能缺乏反选择性或可扩展性.
研究的目的:
- 为了建立一个14-基-6-oxomorphinans的enantioselective *de novo*合成.
- 为了合成关键中间体,特别是4,5-desoxynaltrexone和4,5-desoxynaloxone.
- 评估合成化合物在阿片类受体上的生物活性.
主要方法:
- 进行反选择性 *de novo* 合成策略.
- 用于制备4,5 - 脱氧纳和4,5 - 脱氧纳的药物.
- 在体外生物测定阿片类受体结合和/或活性.
主要成果:
- 成功对标吗啡核心结构进行enantioselective合成.
- 合成的4,5-desoxynaltrexone和4,5-desoxynaloxone的表征和确认.
- 这些新型化合物对阿片类受体的生物活性量化.
结论:
- 描述的合成途径提供了对14-基-6-oxomorphinans.enantiomerically纯的高效访问.
- 合成的类似物与阿片类受体表现出特定的相互作用.
- 这项工作有助于进一步探索基于吗啡的治疗方法.
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