N1-(1-Benzyl-4-piperidyl)-N1-(1H-5-indazolyl)acetamide | 353547-58-7

• 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: N1-(1-Benzyl-4-piperidyl)-N1-(1H-5-indazolyl)acetamide
• 英文别名: N-(1-benzylpiperidin-4-yl)-N-(1H-indazol-5-yl)acetamide
• CAS: 353547-58-7
• 化学式: C₂₁H₂₄N₄O
• 分子量: 348.448
• InChiKey: ORNJYWNEVYQMAV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  52.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N1-(1-Benzyl-4-piperidyl)-N1-(1H-5-indazolyl)acetamide 在 硼烷四氢呋喃络合物 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以75%的产率得到(1-Benzyl-piperidin-4-yl)-ethyl-(1H-indazol-5-yl)-amine
  参考文献：
  名称：

  Design and synthesis of Rho kinase inhibitors (I)

  摘要：

  Several structurally unrelated scaffolds of the Rho kinase inhibitor were designed using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. A docking simulation using the ligand-binding pocket of the Rho kinase model helped to comprehensively understand and to predict the structure-activity relationship of the inhibitors. This understanding was useful for developing new Rho kinase inhibitors of higher potency and selectivity. We identified several potent platforms for developing the Rho kinase inhibitors, namely, pyridine, 1H-indazole, isoquinoline, and phthalimide. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.025
• 作为产物：
  描述：

  5-氨基吲唑 在 吡啶 、 吡啶硼烷 、 溶剂黄146 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 36.0h， 生成 N1-(1-Benzyl-4-piperidyl)-N1-(1H-5-indazolyl)acetamide
  参考文献：
  名称：

  Design and synthesis of Rho kinase inhibitors (I)

  摘要：

  Several structurally unrelated scaffolds of the Rho kinase inhibitor were designed using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. A docking simulation using the ligand-binding pocket of the Rho kinase model helped to comprehensively understand and to predict the structure-activity relationship of the inhibitors. This understanding was useful for developing new Rho kinase inhibitors of higher potency and selectivity. We identified several potent platforms for developing the Rho kinase inhibitors, namely, pyridine, 1H-indazole, isoquinoline, and phthalimide. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.02.025

文献信息

• Nitrogen-containing compounds having kinase inhibitory activity and drugs containing the same
  申请人：——

  公开号：US20040102437A1

  公开（公告）日：2004-05-27

  Compounds having an Rho kinase inhibitory activity. These compounds include the compound of general formula (I): Het-X-Z, pharmaceutically acceptable salts thereof and solvates of the same, wherein Het represents a monocyclic or dicyclic heterocycle group containing at least one nitrogen atom (for example, pyridyl, phthalimido); X represents (i) an —NH—C(═O)—NH-Q1- group, (ii) an —NH—C(═O)-Q2- group, etc. (wherein Q1 and Q2 represent each a bond, alkylene or alkenylene); and Z represents hydrogen, halogeno, a monocyclic, dicyclic ortricyclic carbon cycle or heterocycle, etc. (for example, optionally substituted phenyl).

  具有Rho激酶抑制活性的化合物。这些化合物包括通式（I）的化合物：Het-X-Z，其药学上可接受的盐和溶剂化物，其中Het表示含有至少一个氮原子的单环或双环杂环基团（例如吡啶基，邻苯二甲酰亚胺基）；X表示（i）一个—NH—C(═O)—NH-Q1-基团，（ii）一个—NH—C(═O)-Q2-基团等（其中Q1和Q2分别表示键，烷基或烯基）；Z表示氢，卤素，单环，双环或三环碳环或杂环等（例如可选取代苯基）。
• NITROGEN-CONTAINING COMPOUNDS HAVING KINASE INHIBITORY ACTIVITY AND DRUGS CONTAINING THE SAME
  申请人：KIRIN BEER KABUSHIKI KAISHA

  公开号：EP1256574A1

  公开（公告）日：2002-11-13

  An objective of the present invention is to provide compounds having Rho kinase inhibitory activity. The compounds according to the present invention are those represented by formula (I) or pharmaceutically acceptable salts or solvates thereof:         Het-X-Z     (I) wherein Het represents a monocyclic or bicyclic heterocyclic group containing at least one nitrogen atom, for example, pyridyl or phthalimide; X represents group (i) -NH-C(=O)-NH-Q1-, group (ii) -NH-C(=O)-Q2-, wherein Q1 and Q2 represent a bond, alkylene, or alkenylene, or the like; and Z represents hydrogen, halogen, a monocyclic, bicyclic, or tricyclic carbocyclic group, a heterocyclic group or the like, for example, optionally substituted phenyl.

  本发明的目的是提供具有 Rho 激酶抑制活性的化合物。根据本发明的化合物是式 (I) 所代表的化合物或其药学上可接受的盐或溶液： Het-X-Z (I) 其中 Het 代表含有至少一个氮原子的单环或双环杂环基团，例如吡啶基或邻苯二甲酰亚胺基；X 代表基团(i) -NH-C(=O)-NH-Q1-, 基团(ii) -NH-C(=O)-Q2-, 其中 Q1 和 Q2 代表键、亚烷基或亚烯基或类似物；Z 代表氢、卤素、单环、双环或三环碳环基团、杂环基团或类似基团，例如任选取代的苯基。
• Design and synthesis of Rho kinase inhibitors (II)
  作者：Masayuki Iwakubo、Atsuya Takami、Yuji Okada、Takehisa Kawata、Yoshimichi Tagami、Hiroshi Ohashi、Motoko Sato、Terumi Sugiyama、Kayoko Fukushima、Hiroshi Iijima

  DOI：10.1016/j.bmc.2006.09.052

  日期：2007.1.1

  In a previous study, we identified several structurally unrelated scaffolds of the Rho kinase inhibitor using pharmacophore information obtained from the results of a high-throughput screening and structural information from a homology model of Rho kinase. 1H-Indazole is one of the candidate scaffolds on which a new series of potent Rho kinase inhibitors could be developed. In this study, the detailed structure-activity relationship of 1H-indazole analogues was studied. During this study, we found that the cell-free enzyme inhibitory potential of Rho kinase inhibitors having the 1H-indazole scaffold did not necessarily correlate with their inhibitory potential toward the chemotaxis of cultured cells. The choice of the linker substructure was shown to be an important factor for the 1H-indazole analogues to inhibit the chemotaxis of cells. Optimization of the 1H-indazole inhibitors with respect to the in vitro inhibition of monocyte chemotaxis induced by MCP-1 was carried out. The inhibitory potential was improved both in the cell-free enzyme assay and in the chemotaxis assay. (c) 2006 Elsevier Ltd. All rights reserved.
• US7217722B2
  申请人：——

  公开号：US7217722B2

  公开（公告）日：2007-05-15