N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]cycloleucine | 256476-34-3

• 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: N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]cycloleucine
• 英文别名: 1-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonylamino]cyclopentane-1-carboxylic acid
• CAS: 256476-34-3
• 化学式: C₁₆H₁₈ClN₅O₄S
• 分子量: 411.869
• InChiKey: FKLXTEJVWZKEGC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  169
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]cycloleucine 、 三氟乙酸 在 甲苯 、 异丙醚 、 乙醚 作用下， 以 甲醇 为溶剂， 以to give N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]cycloleucine trifluoroacetate (12 mg)的产率得到N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]cycloleucine trifluoroacetate
  参考文献：
  名称：

  Isoquinolines

  摘要：

  本文披露了式（I）的异喹啉基脲化合物：##STR1## 其中取代基的定义如本文所述，以及其盐，作为尿激酶抑制剂。

  公开号：

  US06093731A1
• 作为产物：
  描述：

  N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]cycloleucine ethyl ester 在 盐酸 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 生成 N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]cycloleucine
  参考文献：
  名称：

  Composition for the treatment of damaged tissue

  摘要：

  描述了一种用于受损组织，如伤口治疗（例如愈合）的药物。该药物包括包含以下成分的组合物：（a）生长因子；和（b）抑制剂；以及可选的（c）药用载体、稀释剂或赋形剂；其中抑制剂可以抑制至少一种在受损组织，如伤口环境中上调的特定不良蛋白质（例如特定蛋白酶）的作用。

  公开号：

  US20030199440A1

文献信息

• ISOQUINOLINES AS UROKINASE INHIBITORS
  申请人：PFIZER INC.

  公开号：EP1077945B1

  公开（公告）日：2003-01-08
• Selective Urokinase-Type Plasminogen Activator Inhibitors. 4. 1-(7-Sulfonamidoisoquinolinyl)guanidines
  作者：Paul V. Fish、Christopher G. Barber、David G. Brown、Richard Butt、Michael G. Collis、Roger P. Dickinson、Brian T. Henry、Valerie A. Horne、John P. Huggins、Elizabeth King、Margaret O'Gara、Dawn McCleverty、Fraser McIntosh、Christopher Phillips、Robert Webster

  DOI：10.1021/jm061066t

  日期：2007.5.1

  1-isoquinolinylguanidines were previously disclosed as potent and selective inhibitors of urokinase-type plasminogen activator (uPA). Further investigation of this template has revealed that incorporation of a 7-sulfonamide group furnishes a new series of potent and highly selective uPA inhibitors. Potency and selectivity can be achieved with sulfonamides derived from a variety of amines and is further enhanced by the incorporation of sulfonamides derived from amino acids. The binding mode of these 1-isoquinolinylguanidines has been investigated by X-ray cocrystallization studies. uPA inhibitor 26 was selected for further evaluation based on its excellent enzyme potency (Ki 10 nM) and selectivity profile (4000-fold versus tPA and 2700-fold versus plasmin). In vitro, compound 26 is able to inhibit exogenous uPA in human chronic wound fluid (IC50=0.89 microM). In vivo, in a porcine acute excisional wound model, following topical delivery, compound 26 is able to penetrate into pig wounds and inhibit exogenous uPA activity with no adverse effect on wound healing parameters. On the basis of this profile, compound 26 (UK-371,804) was selected as a candidate for further preclinical evaluation for the treatment of chronic dermal ulcers.
• DETERMINING THE MECHANISM OF BETA-AMYLOID PEPTIDE GENERATION
  申请人：Elan Pharmaceuticals, Inc.

  公开号：EP1131634A2

  公开（公告）日：2001-09-12
• COMBINATIONS OF GROWTH FACTORS AND I:UPA OR I:MMP FOR THE TREATMENT OF DAMAGED TISSUE
  申请人：Pfizer Limited

  公开号：EP1242120A2

  公开（公告）日：2002-09-25
• US6093731A
  申请人：——

  公开号：US6093731A

  公开（公告）日：2000-07-25