8-phenethyl-8-azabicyclo[3.2.1]octan-3α-yl benzoate hydrochloride | 1272663-25-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-phenethyl-8-azabicyclo[3.2.1]octan-3α-yl benzoate hydrochloride
• 英文别名: 3β-benzoyloxy-8-phenetyl-8-azabicyclo[3.2.1]octane hydrochloride
• CAS: 1272663-25-8
• 化学式: C₂₂H₂₅NO₂*ClH
• 分子量: 371.907
• InChiKey: LZYSSFKFJVJYDE-QYESKELBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  26.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  29.54
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为产物：
  描述：

  3β-benzoyloxy-8-phenetyl-8-azabicyclo[3.2.1]octane 在 盐酸 作用下， 以 乙醚 为溶剂， 以232 mg的产率得到8-phenethyl-8-azabicyclo[3.2.1]octan-3α-yl benzoate hydrochloride
  参考文献：
  名称：

  Structure-based design, synthesis and structure–activity relationships of dibenzosuberyl- and benzoate-substituted tropines as ligands for acetylcholine-binding protein

  摘要：

  Using structure-based optimization procedures on in silico hits, dibenzosuberyl- and benzoate substituted tropines were designed as ligands for acetylcholine-binding protein (AChBP). This protein is a homolog to the ligand binding domain of the nicotinic acetylcholine receptor (nAChR). Distinct SAR is observed between two AChBP species variants and between the alpha 7 and alpha 4 beta 2 nAChR subtype. The AChBP species differences are indicative of a difference in accessibility of a ligand-inducible subpocket. Hereby, we have identified a region that can be scrutinized to achieve selectivity for nicotinic receptor subtypes. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.12.008

文献信息

• Fragment Growing Induces Conformational Changes in Acetylcholine-Binding Protein: A Structural and Thermodynamic Analysis
  作者：Ewald Edink、Prakash Rucktooa、Kim Retra、Atilla Akdemir、Tariq Nahar、Obbe Zuiderveld、René van Elk、Elwin Janssen、Pim van Nierop、Jacqueline van Muijlwijk-Koezen、August B. Smit、Titia K. Sixma、Rob Leurs、Iwan J. P. de Esch

  DOI：10.1021/ja110571r

  日期：2011.4.13

  Optimization of fragment hits toward high-affinity lead compounds is a crucial aspect of fragment-based drug discovery (FBDD). In the current study, we have successfully optimized a fragment by growing into a ligand-inducible subpocket of the binding site of acetylcholine-binding protein (AChBP). This protein is a soluble homologue of the ligand binding domain (LBD) of Cys-loop receptors. The fragment

  针对高亲和力先导化合物的片段命中优化是基于片段的药物发现 (FBDD) 的一个关键方面。在目前的研究中，我们通过生长到乙酰胆碱结合蛋白 (AChBP) 结合位点的配体诱导亚袋中，成功地优化了一个片段。该蛋白质是 Cys 环受体配体结合域 (LBD) 的可溶性同源物。片段优化通过配体复合物的 X 射线结构和使用表面等离子体共振 (SPR) 生物传感器分析和等温滴定量热法 (ITC) 的系统热力学分析进行监测。使用来自不同物种的定点诱变和 AChBP，我们发现热力学结合谱的特定变化表明与 AChBP 的配体诱导亚袋相互作用。