1-chloro-N-phenyl-7-isoquinolinesulphonamide | 223671-79-2

• 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: 1-chloro-N-phenyl-7-isoquinolinesulphonamide
• 英文别名: 1-Chloro-7-phenylsulphamoylisoquinoline；1-chloro-N-phenylisoquinoline-7-sulfonamide
• CAS: 223671-79-2
• 化学式: C₁₅H₁₁ClN₂O₂S
• 分子量: 318.784
• InChiKey: MNNBTDOCTQRBJQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  盐酸胍 、 1-chloro-N-phenyl-7-isoquinolinesulphonamide 在 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 反应 24.5h， 生成 1-guanidino-7-phenylsulphamoylisoquinoline
  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
• 作为产物：
  描述：

  7-溴-1-羟基异喹啉 在 正丁基锂 、 三乙胺 、 三氯氧磷 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 6.58h， 生成 1-chloro-N-phenyl-7-isoquinolinesulphonamide
  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

• [EN] ISOQUINOLINES AS UROKINASE INHIBITORS<br/>[FR] ISOQUINOLINES EN TANT QU'INHIBITEURS DE L'UROKINASE
  申请人：PFIZER LIMITED

  公开号：WO1999020608A1

  公开（公告）日：1999-04-29

  (EN) Compounds of formula (I) and pharmaceutically acceptable salts thereof, wherein one of R1 and R2 is H and the other is N=C(NH2)2 or NHC(=NH)NH2, and the other substituents are as defined herein, are urokinase (uPA) inhibitors.(FR) L'invention concerne des composés de formule (I) et leurs sels pharmaceutiquement acceptables, dans laquelle l'un des R1 et R2 représente H et l'autre représente N=C(NH2)2 ou NHC(=NH)NH2 et les autres substituants sont tels que définis. Les composés sont des inhibiteurs d'urokinase (uPA).

  化合物的式（I）及其药学上可接受的盐，其中R1和R2中的一个是H，另一个是N=C（NH2）2或NHC（=NH）NH2，其他取代基如本文所定义，是尿激酶（uPA）抑制剂。
• Isoquinolines as urokinase inhibitors
  申请人：Pfizer Inc.

  公开号：US06248738B1

  公开（公告）日：2001-06-19

  Compounds of formula (I): and pharmaceutically acceptable salts thereof, wherein one of R1 and R2 is H and the other is N═C(NH2)2 or NHC(═NH)NH2, and the other substituents are as defined herein, are urokinase (uPA) inhibitors.

  式(I)的化合物及其药学上可接受的盐，其中R1和R2中的一个是H，另一个是N═C(NH2)2或NHC(═NH)NH2，其他取代基如本文所定义，是尿激酶（uPA）抑制剂。
• ISOQUINOLINES AS UROKINASE INHIBITORS
  申请人：Pfizer Limited

  公开号：EP1023268A1

  公开（公告）日：2000-08-02
• US6248738B1
  申请人：——

  公开号：US6248738B1

  公开（公告）日：2001-06-19