N-[1-(4-chlorobenzyl)tetrahydro-1H-3-pyrrolyl]-5-isoquinolylamine | 675133-00-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-[1-(4-chlorobenzyl)tetrahydro-1H-3-pyrrolyl]-5-isoquinolylamine
• 英文别名: N-(1-(4-chlorobenzyl)pyrrolidin-3-yl)isoquinolin-5-amine；N-[1-[(4-chlorophenyl)methyl]pyrrolidin-3-yl]isoquinolin-5-amine
• CAS: 675133-00-3
• 化学式: C₂₀H₂₀ClN₃
• 分子量: 337.852
• InChiKey: UGWBCYQPCXKMGF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  4-氯氯苄 在 三氟乙酸 、 potassium carbonate 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 21.0h， 生成 N-[1-(4-chlorobenzyl)tetrahydro-1H-3-pyrrolyl]-5-isoquinolylamine
  参考文献：
  名称：

  ISOQUINOLINE DERIVATIVES HAVING KINASAE INHIBITORY ACTIVITY AND DRUGS CONTAINING THE SAME

  摘要：

  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。

  公开号：

  EP1550660A1

文献信息

• CYTOSKELETAL ACTIVE RHO KINASE INHIBITOR COMPOUNDS, COMPOSITION AND USE
  申请人：Lampe John W.

  公开号：US20080214614A1

  公开（公告）日：2008-09-04

  The present invention is directed to synthetic cytoskeletal active compounds that are inhibitors of rho-associated protein kinase. The present invention is also directed to pharmaceutical compositions comprising such compounds and a pharmaceutically acceptable carrier. The invention is additionally directed to a method of preventing or treating diseases or conditions associated with cytoskeletal reorganization. In one embodiment of the invention, the method treats increased intraocular pressure, such as primary open-angle glaucoma. The method comprises administering to a subject a therapeutically effective amount of a cytoskeletal active compound of Formula I or Formula II, wherein said amount is effective to influence the actomyosin interactions, for example by leading to cellular relaxation and alterations in cell-substratum adhesions.

  本发明涉及一种合成的细胞骨架活性化合物，其为rho相关蛋白激酶的抑制剂。本发明还涉及包含此类化合物和药用载体的制药组合物。此外，本发明还涉及一种预防或治疗与细胞骨架重组相关的疾病或病症的方法。在本发明的一个实施例中，该方法治疗增加的眼内压，如原发性开角型青光眼。该方法包括向受体施用公式I或公式II的细胞骨架活性化合物的治疗有效量，其中该量能够影响肌动蛋白相互作用，例如通过导致细胞松弛和细胞基质附着的改变。
• 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。
• 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.
• METHOD FOR TREATING PULMONARY DISEASES USING RHO KINASE INHIBITOR COMPOUNDS
  申请人：Navratil Tomas

  公开号：US20090325958A1

  公开（公告）日：2009-12-31

  This invention is directed to methods of preventing or treating diseases or conditions of the lungs associated with excessive cell proliferation, remodeling, inflammation, vasoconstriction, bronchoconstriction, airway hyperreactivity and edema. Particularly, this invention is directed to methods of treating pulmonary diseases such as asthma; chronic obstructive pulmonary disease; respiratory tract illness caused by respiratory syncytial virus; pulmonary arterial hypertension; acute respiratory distress syndrome and ventilator induced lung injury; cystic fibrosis; bronchiectasis; alpha-1-antitrypsin deficiency; rhinitis; rhinosinusitis; primary ciliary dyskinesia; pneumonia; bronchiolitis caused by agents other than respiratory syncytial virus; and interstitial lung disease including lymphangioleiomyomatosis; idiopathic pulmonary fibrosis; obliterative bronchiolitis or bronchiolitis obliterans organizing pneumonia due to lung transplantation or HSCT; nonspecific interstitial pneumonia; cryptogenic organizing pneumonia; acute interstitial pneumonia; respiratory bronchiolitis-associated interstitial lung disease; or pulmonary sarcoidosis. The method comprises administering to a subject an effective amount of a rho kinase inhibitor compound to treat the disease.
• METHOD FOR TREATING INFLAMMATORY DISEASES USING RHO KINASE INHIBITOR COMPOUNDS
  申请人：Fulcher Emilee H.

  公开号：US20090325960A1

  公开（公告）日：2009-12-31

  This invention is directed to methods of preventing or treating diseases or conditions associated with excessive cell proliferation, remodeling, edema and inflammation. Particularly, this invention is directed to methods of treating inflammatory diseases or conditions such as rheumatoid arthritis and inflammatory bowel disease. The method comprises identifying a subject in need of the treatment, and administering to the subject an effective amount of a compound of a novel rho kinase inhibitor compound to treat the disease.