Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, UK.
Bioorg Med Chem Lett. 2012 Mar 15;22(6):2200-3. doi: 10.1016/j.bmcl.2012.01.099. Epub 2012 Feb 2.
3-Azabicyclo[3.1.0]hexane compounds were designed as novel achiral μ opioid receptor ligands for the treatment of pruritus in dogs. In this paper, we describe the SAR of this class of opioid ligand, highlighting changes to the lead structure which led to compounds having picomolar binding affinity, selective for the μ receptor over δ and κ subtypes. Some subtleties of functional activity will also be described.
3-氮杂双环[3.1.0]己烷类化合物被设计为新型非手性μ阿片受体配体，用于治疗犬瘙痒。本文描述了这一类阿片类配体的 SAR，重点介绍了导致化合物具有皮摩尔结合亲和力的先导结构变化，对μ受体具有选择性，而对 δ 和 κ 亚型无活性。还将描述一些功能活性的细微差别。
