2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxo-N-(2-oxo-1,3-dihydroindol-5-yl)acetamide | 948021-18-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxo-N-(2-oxo-1,3-dihydroindol-5-yl)acetamide
• CAS: 948021-18-9
• 化学式: C₂₀H₁₉ClN₄O₃
• 分子量: 398.849
• InChiKey: KWGVEBNVVWUMQT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1-(4-氯苯基)哌嗪 在 4-二甲氨基吡啶 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 2-[4-(4-chlorophenyl)piperazin-1-yl]-2-oxo-N-(2-oxo-1,3-dihydroindol-5-yl)acetamide
  参考文献：
  名称：

  通过支架跳跃和药代动力学特性优化发现NR2B选择性拮抗剂。

  摘要：

  选择性N-甲基-d-天冬氨酸受体亚基2B（NR2B）拮抗剂具有作为止痛药的潜力，并且不会引起与非选择性N-甲基-d-天冬氨酸（NMDA）拮抗剂相关的副作用。使用脚手架跳方法，我们以前确定异恶唑衍生物4作为有效的选择性NR2B拮抗剂。在这项研究中，异恶唑衍生物4的进一步跳跃和对其药代动力学特性的优化导致发现了口服生物利用性化合物6v。在一项大鼠镇痛研究中，6v表现出对神经性疼痛的镇痛作用。

  DOI：

  10.1016/j.bmcl.2019.02.017

文献信息

• NIROGENOUS HETEROCYCLIC DERIVATIVES SUBSTITUTED WITH CYCLIC GROUPS
  申请人：SHIONOGI & CO., LTD.

  公开号：EP1988077A1

  公开（公告）日：2008-11-05

  It was found out that the nitrogen-containing heterocyclic derivative represented by the formula (I) specifically binds to a receptor of NR1/NR2B, and is used as a NR2B receptor antagonist. A compound represented by: wherein Z is N or CR1, A1 is a nitrogen-containing aromatic monocyclic group which is optionally substituted, a nitrogen-containing aromatic fused cyclic group which is optionally substituted etc., A2 is an aromatic hydrocarbon cyclic group or an aromatic heterocyclic group, each optionally having a substituent, R1, R2, Ra, Rb, Rc and Rd are each independently hydrogen, hydroxy, etc., w is 2 or 3, t is 1 or 2, X is -(CR3R4)m-, -CO(CR3R4)n-, -CONR5(CR3R4)n- etc., m is an integer of 1 to 4, n is an integer of 0 to 4, R3 and R4 are each independently hydrogen, halogen, hydroxy etc., and R5 is hydrogen or lower alkyl, or a pharmaceutically acceptable salt, or a solvate thereof.

  研究发现，由式（I）代表的含氮杂环衍生物能与 NR1/NR2B 受体特异性结合，可用作 NR2B 受体拮抗剂。 由式（I）代表的化合物 其中 Z 是 N 或 CR1，A1 是任选被取代的含氮芳香族单环基团、任选被取代的含氮芳香族融合环基团等，A2 是芳香烃环基团或芳香杂环基团，各自任选具有一个取代基，R1、R2、Ra、Rb、Rc 和 Rd 各自独立地是氢、羟基等、w 是 2 或 3，t 是 1 或 2，X 是-(CR3R4)m-、-CO(CR3R4)n-、-CONR5(CR3R4)n- 等，m 是 1 至 4 的整数，n 是 0 至 4 的整数，R3 和 R4 各自独立地是氢、卤素、羟基等，R5 是氢或低级烷基、 或其药学上可接受的盐或溶液。
• NITROGEN-CONTAINING HETEROCYCLE DERIVATIVES SUBSTITUTED WITH CYCLIC GROUP
  申请人：Masui Moriyasu

  公开号：US20090062261A1

  公开（公告）日：2009-03-05

  It was found out that the nitrogen-containing heterocyclic derivative represented by the formula (I) specifically binds to a receptor of NR1/NR2B, and is used as a NR2B receptor antagonist. A compound represented by: wherein Z is N or CR 1 , A 1 is a nitrogen-containing aromatic monocyclic group which is optionally substituted, a nitrogen-containing aromatic fused cyclic group which is optionally substituted etc., A 2 is an aromatic hydrocarbon cyclic group or an aromatic heterocyclic group, each optionally having a substituent, R 1 , R 2 , R a , R b , R c and R d are each independently hydrogen, hydroxy, etc., w is 2 or 3, t is 1 or 2, X is —(CR 3 R 4 )m-, —CO(CR 3 R 4 )n-, —CONR 5 (CR 3 R 4 )n- etc., m is an integer of 1 to 4, n is an integer of 0 to 4, R 3 and R 4 are each independently hydrogen, halogen, hydroxy etc., and R 5 is hydrogen or lower alkyl, or a pharmaceutically acceptable salt, or a solvate thereof.
• US7935706B2
  申请人：——

  公开号：US7935706B2

  公开（公告）日：2011-05-03
• Discovery of NR2B-selective antagonists via scaffold hopping and pharmacokinetic profile optimization
  作者：Kosuke Anan、Moriyasu Masui、Aya Tazawa、Minoru Tomida、Yoshihiro Haga、Masaharu Kume、Shoichi Yamamoto、Shunji Shinohara、Hiroki Tsuji、Shinji Shimada、Shigenori Yagi、Nobuyoshi Hasebe、Hiroyuki Kai

  DOI：10.1016/j.bmcl.2019.02.017

  日期：2019.5

  Selective N-methyl-d-aspartate receptor subunit 2B (NR2B) antagonists show potential as analgesic drugs, and do not cause side effects associated with non-selective N-methyl-d-aspartate (NMDA) antagonists. Using a scaffold-hopping approach, we previously identified isoxazole derivative 4 as a potent selective NR2B antagonist. In this study, further scaffold hopping of isoxazole derivative 4 and optimization

  选择性N-甲基-d-天冬氨酸受体亚基2B（NR2B）拮抗剂具有作为止痛药的潜力，并且不会引起与非选择性N-甲基-d-天冬氨酸（NMDA）拮抗剂相关的副作用。使用脚手架跳方法，我们以前确定异恶唑衍生物4作为有效的选择性NR2B拮抗剂。在这项研究中，异恶唑衍生物4的进一步跳跃和对其药代动力学特性的优化导致发现了口服生物利用性化合物6v。在一项大鼠镇痛研究中，6v表现出对神经性疼痛的镇痛作用。