发现并合成了一类具有 3-氮杂双环[3.1.0]己烷核心的新型阿片类配体。“神奇甲基”使结合提高了 35 倍的实例。
Discovery and synthesis of a new class of opioid ligand having a 3-azabicyclo[3.1.0]hexane core. An example of a 'magic methyl' giving a 35-fold improvement in binding.
机构信息
Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, UK.
出版信息
Bioorg Med Chem Lett. 2011 Aug 1;21(15):4608-11. doi: 10.1016/j.bmcl.2011.05.132. Epub 2011 Jun 16.
PMID:21737265
Abstract
In looking for a novel achiral μ opioid receptor antagonist for the treatment of pruritus, we designed and synthesised azabicyclo[3.1.0]hexane compounds as a new class of opioid ligand. During optimisation, an addition of a single methyl resulted in a 35-fold improvement in binding. An early example from the series had excellent μ opioid receptor antagonist antagonist activity and was very effective in an in vivo pruritus study.
摘要
在寻找一种新型非手性 μ 阿片受体拮抗剂以治疗瘙痒症时，我们设计并合成了氮杂双环[3.1.0]己烷类化合物作为一类新型阿片类配体。在优化过程中，增加一个甲基可使结合活性提高 35 倍。该系列的早期实例具有优异的 μ 阿片受体拮抗剂拮抗活性，在体内瘙痒研究中非常有效。
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