tert-butyl (2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)ethyl)carbamate | 1610591-72-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: tert-butyl (2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)ethyl)carbamate
• 英文别名: tert-butyl N-[2-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]ethyl]carbamate
• CAS: 1610591-72-4
• 化学式: C₁₈H₂₇ClN₂O₃
• 分子量: 354.877
• InChiKey: BHOHPRFNAQMPCI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.61
• 拓扑面积：
  61.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl (2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)ethyl)carbamate 在 盐酸 、 三乙胺 作用下， 以 1,4-二氧六环 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 65.0h， 生成 1-(2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)ethyl)-3-(2-(2,5-dioxo-2,5-dihydro-1H-pyrrol-1-yl)ethyl)urea
  参考文献：
  名称：

  强效氟哌啶醇衍生物与多巴胺D2受体共价结合

  摘要：

  多巴胺D 2受体（D 2 R）是用于治疗包括精神分裂症在内的多种神经系统疾病的常见药物靶标。亚型选择性D 2 R拮抗剂的基于结构的设计需要受体的高分辨率晶体结构和药理学工具，以促进对蛋白质-配体相互作用的更好理解。最近，我们报道了一种化学活化的多巴胺衍生物（FAUC150）的开发，该衍生物旨在共价结合多巴胺D 2受体的L94C突变体。我们以FAUC150为模板，阐述了有效的抗精神病药物氟哌啶醇形成共价D 2的不可逆类似物的设计和合成。R-配体配合物。在放射性配体消耗实验中，二硫键和Michael受体官能化的化合物显示出显着的受体亲和力和不可逆的结合特性。

  DOI：

  10.1016/j.bmc.2017.06.034
• 作为产物：
  描述：

  二碳酸二叔丁酯 在 三乙胺 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 7.5h， 生成 tert-butyl (2-(4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl)ethyl)carbamate
  参考文献：
  名称：

  Structure–Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D₂ Receptor

  摘要：

  Biased agonism at GPCRs highlights the potential for the discovery and design of pathway-selective ligands and may confer therapeutic advantages to ligands targeting the dopamine D-2 receptor (D2R). We investigated the determinants of efficacy, affinity, and bias for three privileged structures for the D2R, exploring changes to linker length and incorporation of a heterocyclic unit. Profiling the compounds in two signaling assays (cAMP and pERK1/2) allowed us to identify and quantify determinants of biased agonism at the D2R. Substitution on the phenylpiperazine privileged structures (2-methoxy vs 2,3-dichloro) influenced bias when the thienopyridine heterocycle was absent. Upon inclusion of the thienopyridine unit, the substitution pattern (4,6-dimethyl vs 5-chloro-6-methoxy-4-methyl) had a significant effect on bias that overruled the effect of the phenylpiperazine substitution pattern. This latter observation could be reconciled with an extended binding mode for these compounds, whereby the interaction of the heterocycle with a secondary binding pocket may engender bias.

  DOI：

  10.1021/jm500457x

文献信息

• Potent haloperidol derivatives covalently binding to the dopamine D2 receptor
  作者：Tobias Schwalbe、Jonas Kaindl、Harald Hübner、Peter Gmeiner

  DOI：10.1016/j.bmc.2017.06.034

  日期：2017.10

  chemically activated dopamine derivative (FAUC150) designed to covalently bind the L94C mutant of the dopamine D2 receptor. Using FAUC150 as a template, we elaborated the design and synthesis of irreversible analogs of the potent antipsychotic drug haloperidol forming covalent D2R-ligand complexes. The disulfide- and Michael acceptor-functionalized compounds showed significant receptor affinity and an irreversible

  多巴胺D 2受体（D 2 R）是用于治疗包括精神分裂症在内的多种神经系统疾病的常见药物靶标。亚型选择性D 2 R拮抗剂的基于结构的设计需要受体的高分辨率晶体结构和药理学工具，以促进对蛋白质-配体相互作用的更好理解。最近，我们报道了一种化学活化的多巴胺衍生物（FAUC150）的开发，该衍生物旨在共价结合多巴胺D 2受体的L94C突变体。我们以FAUC150为模板，阐述了有效的抗精神病药物氟哌啶醇形成共价D 2的不可逆类似物的设计和合成。R-配体配合物。在放射性配体消耗实验中，二硫键和Michael受体官能化的化合物显示出显着的受体亲和力和不可逆的结合特性。
• Structure–Activity Relationships of Privileged Structures Lead to the Discovery of Novel Biased Ligands at the Dopamine D₂ Receptor
  作者：Monika Szabo、Carmen Klein Herenbrink、Arthur Christopoulos、J. Robert Lane、Ben Capuano

  DOI：10.1021/jm500457x

  日期：2014.6.12

  Biased agonism at GPCRs highlights the potential for the discovery and design of pathway-selective ligands and may confer therapeutic advantages to ligands targeting the dopamine D-2 receptor (D2R). We investigated the determinants of efficacy, affinity, and bias for three privileged structures for the D2R, exploring changes to linker length and incorporation of a heterocyclic unit. Profiling the compounds in two signaling assays (cAMP and pERK1/2) allowed us to identify and quantify determinants of biased agonism at the D2R. Substitution on the phenylpiperazine privileged structures (2-methoxy vs 2,3-dichloro) influenced bias when the thienopyridine heterocycle was absent. Upon inclusion of the thienopyridine unit, the substitution pattern (4,6-dimethyl vs 5-chloro-6-methoxy-4-methyl) had a significant effect on bias that overruled the effect of the phenylpiperazine substitution pattern. This latter observation could be reconciled with an extended binding mode for these compounds, whereby the interaction of the heterocycle with a secondary binding pocket may engender bias.