4-(5-isoquinolylamino)-1-cyclohexanone | 353561-85-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 4-(5-isoquinolylamino)-1-cyclohexanone
• 英文别名: 4-(isoquinolin-5-ylamino)cyclohexanone；4-(isoquinolin-5-ylamino)cyclohexan-1-one
• CAS: 353561-85-0
• 化学式: C₁₅H₁₆N₂O
• 分子量: 240.305
• InChiKey: NWNUEAXOCFIDGL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  42
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  甲胺 、 4-(5-isoquinolylamino)-1-cyclohexanone 在 三乙酰氧基硼氢化钠 作用下， 以 甲醇 为溶剂， 以69%的产率得到4-N-isoquinolin-5-yl-1-N-methylcyclohexane-1,4-diamine
  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-氨基异喹啉 、 1,4-环己二酮单乙二醇缩酮 在 吡啶硼烷 、 溶剂黄146 作用下， 以 甲醇 为溶剂， 反应 21.0h， 以5.80 g的产率得到4-(5-isoquinolylamino)-1-cyclohexanone
  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：Kyowa Hakko Kirin Co., Ltd.

  公开号：EP1256574B1

  公开（公告）日：2012-01-18
• US7217722B2
  申请人：——

  公开号：US7217722B2

  公开（公告）日：2007-05-15
• Design and synthesis of rho kinase inhibitors (III)
  作者：Masayuki Iwakubo、Atsuya Takami、Yuji Okada、Takehisa Kawata、Yoshimichi Tagami、Motoko Sato、Terumi Sugiyama、Kayoko Fukushima、Shinichiro Taya、Mutsuki Amano、Kozo Kaibuchi、Hiroshi Iijima

  DOI：10.1016/j.bmc.2006.10.028

  日期：2007.1

  The structure-activity relationship of Rho kinase inhibitors bearing an isoquinoline scaffold was studied. N-(1-Benzyl-3-pyrrolidyl)-N-(5-isoquinolyl)amine analogues were optimized with respect to their inhibitory potencies for the enzyme and for chemotaxis. The potent analogues were further evaluated by an ex vivo test in which the selected compounds were orally administered to rats, and the Rho kinase inhibitory potency observed in the rat serum was evaluated 3 h after the administration. Compound 23g showed a high level of Rho kinase inhibitory activity in the rat serum and was stable in an in vitro metabolic test using a microsomal cytochrome preparation. The (R)-isomer of 23g displayed a higher level of inhibitory potency than the (S)-isomer in a cell-free kinase assay and in the cell migration assay (IC50ENZ = 25 nM and IC50MCP = 1 mu M). The (R)-isomer successfully inhibited the phosphorylation of MBS (myosin-binding subunit) in cells. (c) 2006 Published by Elsevier Ltd.
• Design and synthesis of Rho kinase inhibitors (I)
  作者：Atsuya Takami、Masayuki Iwakubo、Yuji Okada、Takehisa Kawata、Hideharu Odai、Nobuaki Takahashi、Kazutoshi Shindo、Kaname Kimura、Yoshimichi Tagami、Mika Miyake、Kayoko Fukushima、Masaki Inagaki、Mutsuki Amano、Kozo Kaibuchi、Hiroshi Iijima

  DOI：10.1016/j.bmc.2004.02.025

  日期：2004.5

  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.