ethyl 4-((4-(2-methylbenzamido)naphthalene)-1-sulfonamido)piperidine-1-carboxylate

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: ethyl 4-((4-(2-methylbenzamido)naphthalene)-1-sulfonamido)piperidine-1-carboxylate
• 英文别名: 4-[4-(2-methyl-benzoylamino)-naphthalene-1-sulfonylamino]-piperidine-1-carboxylic acid ethyl ester；CCR8 antagonist 1；ethyl 4-[[4-[(2-methylbenzoyl)amino]naphthalen-1-yl]sulfonylamino]piperidine-1-carboxylate
• 化学式: C₂₆H₂₉N₃O₅S
• 分子量: 495.599
• InChiKey: LGJRRERRFSZFTJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  35
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  113
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  4-溴-1-萘磺酰氯 在 palladium diacetate 、 caesium carbonate 、 三乙胺 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 33.0h， 生成 ethyl 4-((4-(2-methylbenzamido)naphthalene)-1-sulfonamido)piperidine-1-carboxylate
  参考文献：
  名称：

  在溴萘支架上钯催化的交叉偶联反应寻找新型人类 CC 趋化因子受体 8 (CCR8) 拮抗剂

  摘要：

  已知萘磺酰胺支架具有 CCR8 拮抗特性。为了扩展此类化合物的构效关系研究，在溴萘前体上进行了各种钯催化的交叉偶联反应，产生了不同的库。这些化合物在结合和钙动员测定中显示出 CCR8 拮抗特性，IC 50值在 0.2 – 10 µM 范围内。与原始先导化合物相比，活性降低是通过同源分子模型合理化的。

  DOI：

  10.1016/j.bioorg.2020.104560

文献信息

• Palladium-catalyzed cross-coupling reactions on a bromo-naphthalene scaffold in the search for novel human CC chemokine receptor 8 (CCR8) antagonists
  作者：Yenthel Verhaegen、Libao Liu、Tien T. Nguyen、Tom Van Loy、Arnout R.D. Voet、Dominique Schols、Wim Dehaen、Steven De Jonghe

  DOI：10.1016/j.bioorg.2020.104560

  日期：2021.2

  The naphthalene sulfonamide scaffold is known to possess CCR8 antagonistic properties. In order to expand the structure–activity relationship study of this compound class, a variety of palladium-catalyzed cross-coupling reactions was performed on a bromo-naphthalene precursor yielding a diverse library. These compounds displayed CCR8 antagonistic properties in binding and calcium mobilization assays

  已知萘磺酰胺支架具有 CCR8 拮抗特性。为了扩展此类化合物的构效关系研究，在溴萘前体上进行了各种钯催化的交叉偶联反应，产生了不同的库。这些化合物在结合和钙动员测定中显示出 CCR8 拮抗特性，IC 50值在 0.2 – 10 µM 范围内。与原始先导化合物相比，活性降低是通过同源分子模型合理化的。
• Aryl sulfonamides useful as inhibitors of chemokine receptor activity
  申请人：Dai Mingshi

  公开号：US20050085518A1

  公开（公告）日：2005-04-21

  The present invention provides compounds of general formula I: or a pharmaceutically acceptable salt thereof, wherein R 1 , X, Z, R 2 , X., Ar, n, R 3 and R 4 are defined generally and in subsets herein. Compounds of the invention are inhibitors of CCR8 and accordingly are useful for the treatment of a variety of inflammatory and allergic disorders.

  本发明提供一般式I的化合物:或其药学上可接受的盐，其中R1、X、Z、R2、X.、Ar、n、R3和R4在本文中一般和子集中定义。本发明的化合物是CCR8的抑制剂，因此可用于治疗各种炎症和过敏性疾病。
• CCR8 Inhibitors
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20040209948A1

  公开（公告）日：2004-10-21

  Disclosed are CCR8 inhibitors represented by Structural Formulas (I): 1 The variables in Structural Formula (I) are described herein. Also disclosed are methods of treating a subject with a CCR8 mediated condition, especially asthma, by administering one of the disclosed CCR8 inhibitors to the subject.

  本发明涉及由结构式（I）表示的CCR8抑制剂：1结构式（I）中的变量在此文中进行了描述。本发明还涉及通过向受试者给予所披露的CCR8抑制剂之一来治疗CCR8介导的疾病，特别是哮喘的方法。
• CCR8 inhibitors
  申请人：Millennium Pharmaceuticals, Inc.

  公开号：US20040224978A1

  公开（公告）日：2004-11-11

  Disclosed is an inhibitor of CCR8 that is represented by Structural Formula (I): 1 Also disclosed are pharmaceutical compositions comprising a pharmaceutically acceptable carrier or diluent and a CCR8 inhibitor represented by Structural Formula (I). Also disclosed is a method of treating inflammatory disorders in a subject by administering a CCR8 inhibitor to the subject.

  本发明揭示了一种由结构式(I)所代表的CCR8抑制剂：1。还揭示了包含药学上可接受的载体或稀释剂以及由结构式(I)所代表的CCR8抑制剂的药物组合物。同时还揭示了通过向受试者施用CCR8抑制剂来治疗炎症性疾病的方法。
• Design, Synthesis, and Evaluation of Naphthalene-Sulfonamide Antagonists of Human CCR8
  作者：Tracy J. Jenkins、Bing Guan、Mingshi Dai、Gang Li、Thomas E. Lightburn、Shan Huang、B. Scott Freeze、Douglas F. Burdi、Swanee Jacutin-Porte、Robert Bennett、Weirong Chen、Charles Minor、Shomir Ghosh、Christopher Blackburn、Kenneth M. Gigstad、Matthew Jones、Roland Kolbeck、Wei Yin、Sean Smith、Daniel Cardillo、Timothy D. Ocain、Geraldine C. Harriman

  DOI：10.1021/jm061118e

  日期：2007.2.8

  The design, synthesis, and structure-activity relationship development of naphthalene-derived human CCR8 antagonists is described. In vitro binding assay results of these investigations are reported, critical interactions of the antagonists with CCR8 are defined, and preliminary physicochemical and pharmacokinetic data for the naphthalene scaffold are presented.