N-[1-(3-chlorobenzyl)-3-piperidyl]-5-isoquinolylamine | 675133-19-4

• 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: N-[1-(3-chlorobenzyl)-3-piperidyl]-5-isoquinolylamine
• 英文别名: N-(1-(3-chlorobenzyl)piperidin-3-yl)isoquinolin-5-amine；N-[1-[(3-chlorophenyl)methyl]piperidin-3-yl]isoquinolin-5-amine
• CAS: 675133-19-4
• 化学式: C₂₁H₂₂ClN₃
• 分子量: 351.879
• InChiKey: RBWIABZDNXFVEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  28.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  N-BOC-3-羟基哌啶 在 trioxide-trimethylamine 、 三乙酰氧基硼氢化钠 、 溶剂黄146 、 sodium sulfate 、 三乙胺 、 三氟乙酸 作用下， 以 氯仿 、 二甲基亚砜 为溶剂， 反应 36.0h， 生成 N-[1-(3-chlorobenzyl)-3-piperidyl]-5-isoquinolylamine
  参考文献：
  名称：

  Design and synthesis of rho kinase inhibitors (III)

  摘要：

  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.

  DOI：

  10.1016/j.bmc.2006.10.028

文献信息

• ISOQUINOLINE DERIVATIVES HAVING KINASAE INHIBITORY ACTIVITY AND DRUGS CONTAINING THE SAME
  申请人：KIRIN BEER KABUSHIKI KAISHA

  公开号：EP1550660A1

  公开（公告）日：2005-07-06

  An objective of the present invention is to provide compounds having Rho kinase inhibitory activity and useful for the treatment of diseases mediated by Rho kinase. The compounds according to the present invention are those represented by formula (I) or pharmaceutically acceptable salts or solvates thereof: wherein Q represents phenyl, pyridyl, pyrrolyl, thienyl, or furyl; these groups are optionally substituted by one or two halogens or alkyl, nitro, or amino groups; and p is 2 or 3.

  本发明的一个目标是提供具有Rho激酶抑制活性并用于治疗由Rho激酶介导的疾病的化合物。根据本发明的化合物是由以下式（I）表示的，或者其药学上可接受的盐或溶剂：其中Q代表苯基、吡啶基、吡咯基、噻吩基或呋喃基；这些基团可以选择地被一个或两个卤素或烷基、硝基或氨基取代；而p为2或3。
• Isoquinoline derivatives having kinasae inhibitory activity and drugs containing the same
  申请人：Iwakubo Masayuki

  公开号：US20060167043A1

  公开（公告）日：2006-07-27

  An objective of the present invention is to provide compounds having Rho kinase inhibitory activity and useful for the treatment of diseases mediated by Rho kinase. The compounds according to the present invention are those represented by formula (I) or pharmaceutically acceptable salts or solvates thereof: wherein Q represents phenyl, pyridyl, pyrrolyl, thienyl, or furyl; these groups are optionally substituted by one or two halogens or alkyl, nitro, or amino groups; and p is 2 or 3.

  本发明的目的是提供具有 Rho 激酶抑制活性并可用于治疗由 Rho 激酶介导的疾病的化合物。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： 其中 Q 代表苯基、吡啶基、吡咯基、噻吩基或呋喃基；这些基团任选被一个或两个卤素或烷基、硝基或氨基取代；且 p 为 2 或 3。
• US7615564B2
  申请人：——

  公开号：US7615564B2

  公开（公告）日：2009-11-10
• 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.