9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester | 1246508-51-9

• 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: 9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl 9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carboxylate
• CAS: 1246508-51-9
• 化学式: C₂₀H₂₉FN₂O₂
• 分子量: 348.461
• InChiKey: LAUIEVJLCXQNSC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  32.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 3-(4-Fluorophenyl)-3,9-diazaspiro[5.5]undecane
  参考文献：
  名称：

  具有Arylated Diazaspiro Alkane核心的高选择性多巴胺D3受体拮抗剂。

  摘要：

  合成了一系列具有重氮杂螺烷核心的有效和选择性D 3受体（D 3 R）类似物。化合物的放射性配体结合11，14，图15A，和图15C显示有利d 3 R有着亲和性（ķ我= 12-25.6 1nM）和分别为d高度选择性3 - [R VS d 3 R（范围从264-〜905倍）。使用我们先前报道的10–20分钟台式C–N交叉偶联方法，可以实现这些新颖的配体体系结构的变化，从而提供了多种芳基化的diazaspiro前体。

  DOI：

  10.1021/acs.jmedchem.7b01248
• 作为产物：
  描述：

  1-氯-4-氟苯 、 叔丁基3,9-二氮杂螺[5.5]十一烷-3-甲酸酯 在 tris-(dibenzylideneacetone)dipalladium(0) 、 sodium t-butanolate 、 2-二环己基磷-2',6'-二异丙氧基-1,1'-联苯 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.33h， 以76%的产率得到9-(4-fluorophenyl)-3,9-diazaspiro[5.5]undecane-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Pd-catalyzed arylation of linear and angular spirodiamine salts under aerobic conditions

  摘要：

  Application of Buchwald-Hartwig catalysis for development of biologically relevant arylspirodiamine compounds is reported. This synthetic methodology requires no inert atmosphere and affords yields up to 93% in just 20 min. Linear and sterically hindered angular spirodiamines in salt and free-base form are coupled with electron-rich and-withdrawing aryl chlorides, demonstrating a broad scope and applicability of this protocol. (C) 2016 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2016.12.063

文献信息

• Substituted Spiro-amide Compounds
  申请人：Schunk Stefan

  公开号：US20100249095A1

  公开（公告）日：2010-09-30

  Substituted spiro-amide compounds corresponding to formula I in which R5 through R8, D, X, Y and Z have defined meanings, processes for preparing such spiro-amide compounds, pharmaceutical compositions containing such compounds, and methods of using such spiro-amide compounds for treating and/or inhibiting disorders or disease states mediated at least in part by the bradykinin 1 receptor.

  将与式I相对应的螺环酰胺化合物替代为R5至R8、D、X、Y和Z具有定义含义的过程，用于制备这种螺环酰胺化合物，含有这种化合物的药物组合物，以及使用这种螺环酰胺化合物治疗和/或抑制至少部分由激肽酶1受体介导的疾病或疾病状态的方法。
• Substituted spiro-amide compounds
  申请人：Schunk Stefan

  公开号：US08455475B2

  公开（公告）日：2013-06-04

  Substituted spiro-amide compounds corresponding to formula I in which R5 through R8, D, X, Y and Z have defined meanings, processes for preparing such spiro-amide compounds, pharmaceutical compositions containing such compounds, and methods of using such spiro-amide compounds for treating and/or inhibiting disorders or disease states mediated at least in part by the bradykinin 1 receptor.

  本发明涉及代表式I的取代螺环酰胺化合物，其中R5到R8、D、X、Y和Z具有定义的含义，制备这种螺环酰胺化合物的方法，包含这种化合物的制药组合物，以及使用这种螺环酰胺化合物治疗和/或抑制至少部分由布雷金肽1受体介导的疾病或疾病状态的方法。
• Substituted Spiro-Amide Compounds
  申请人：Gruenenthal GmbH

  公开号：US20130231327A1

  公开（公告）日：2013-09-05

  Substituted spiro-amide compounds corresponding to formula I in which R 5 through R 8 , D, X, Y and Z have defined meanings, processes for preparing such spiro-amide compounds, pharmaceutical compositions containing such compounds, and methods of using such spiro-amide compounds for treating and/or inhibiting disorders or disease states mediated at least in part by the bradykinin 1 receptor.

  本发明提供了对应于式I的取代螺环酰胺化合物，其中R5至R8、D、X、Y和Z具有定义的含义，制备这种螺环酰胺化合物的过程，含有这种化合物的药物组合物以及使用这种螺环酰胺化合物治疗和/或抑制至少部分由激肽酶1受体介导的疾病或疾病状态的方法。
• Leveraging a Low-Affinity Diazaspiro Orthosteric Fragment to Reduce Dopamine D₃ Receptor (D₃R) Ligand Promiscuity across Highly Conserved Aminergic G-Protein-Coupled Receptors (GPCRs)
  作者：Sean W. Reilly、Aladdin A. Riad、Chia-Ju Hsieh、Kristoffer Sahlholm、Daniel A. Jacome、Suzy Griffin、Michelle Taylor、Chi-Chang Weng、Kuiying Xu、Nathan Kirschner、Robert R. Luedtke、Christopher Parry、Shipra Malhotra、John Karanicolas、Robert H. Mach

  DOI：10.1021/acs.jmedchem.9b00412

  日期：2019.5.23

  Previously, we reported a 3-(2-methoxyphenyl)-9-(3-((4-methyl-5-phenyl-4H-1,2,4-triazol-3-yl)thio)-propyl)-3,9-diazaspiro[5.5]undecane (1) compound with excellent dopamine D-3 receptor (D3R) affinity (D3R K-i = 12.0 nM) and selectivity (D2R/D3R ratio = 905). Herein, we present derivatives of 1 with comparable D3R affinity (32, D3R K-i = 3.2 nM, D2R/D3R ratio = 60) and selectivity (30, D3R K-i = 21.0 nM, D2R/D3R ratio = 934). Fragmentation of 1 revealed orthosteric fragment 5a to express an unusually low D3R affinity (K-i = 2.7 mu M). Compared to piperazine congener 31, which retains a high-affinity orthosteric fragment (5d, D3R K-i = 23.9 nM), 1 was found to be more selective for the D3R among D-1- and D-2-like receptors and exhibited negligible off-target interactions at serotoninergic and adrenergic G-protein-coupled receptors (GPCRs), common off-target sites for piperazine-containing D3R scaffolds. This study provides a unique rationale for implementing weakly potent orthosteric fragments into D3R ligand systems to minimize drug promiscuity at other aminergic GPCR sites.
• SUBSTITUTED SPIRO-AMIDE COMPOUNDS
  申请人：Grünenthal GmbH

  公开号：EP2411381A1

  公开（公告）日：2012-02-01