N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(cyclopentylmethyl)glycine hydrochloride

• 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]-N-(cyclopentylmethyl)glycine hydrochloride
• 英文别名: 2-[[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]sulfonyl-(cyclopentylmethyl)amino]acetic acid;hydrochloride
• 化学式: C₁₈H₂₂ClN₅O₄S*ClH
• 分子量: 476.384
• InChiKey: BLGALJLRMMYDNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.48
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  160
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  7-溴-1,4-二氯异喹啉 在 盐酸 、 正丁基锂 、 sodium hydride 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙二醇二甲醚 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 50.08h， 生成 N-[(4-chloro-1-guanidino-7-isoquinolinyl)sulphonyl]-N-(cyclopentylmethyl)glycine hydrochloride
  参考文献：
  名称：

  Selective Urokinase-Type Plasminogen Activator Inhibitors. 4. 1-(7-Sulfonamidoisoquinolinyl)guanidines

  摘要：

  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.

  DOI：

  10.1021/jm061066t

文献信息

• Composition for the treatment of damaged tissue
  申请人：Pfizer Inc.

  公开号：US20030199440A1

  公开（公告）日：2003-10-23

  A pharmaceutical for use in damaged tissue, such as wound, treatment (e.g. healing) is described. The pharmaceutical comprising a composition which comprises: (a) a growth factor; and (b) an inhibitor agent; and optionally (c) a pharmaceutically acceptable carrier, diluent or excipient; wherein the inhibitor agent can inhibit the action of at least one specific adverse protein (e.g. a specific protease) that is upregulated in a damaged tissue, such as a wound, environment.

  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。
• Isoquinolines
  申请人：——

  公开号：US06093731A1

  公开（公告）日：2000-07-25

  Isoquinolinylguanidine compounds of formula (I): ##STR1## wherein the substituents are as defined herein, and salts thereof, are disclosed as urokinase inhibitors.

  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。
• ISOQUINOLINES AS UROKINASE INHIBITORS
  申请人：PFIZER INC.

  公开号：EP1077945B1

  公开（公告）日：2003-01-08
• 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