1,4-二氯-7-异喹啉磺酰氯 | 223671-80-5

• 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
• 中文名称: 1,4-二氯-7-异喹啉磺酰氯
• 英文名称: 1,4-dichloro-7-isoquinolinesulfonyl chloride
• 英文别名: 1,4-dichloro-7-isoquinolinesulphonyl chloride；7-chlorosulphonyl-1,4-dichloroisoquinoline；1,4-Dichloroisoquinoline-7-sulfonyl chloride
• CAS: 223671-80-5
• 化学式: C₉H₄Cl₃NO₂S
• 分子量: 296.561
• InChiKey: UVTOICZCRRXFKE-UHFFFAOYSA-N

物化性质

• 熔点：
  97-99°C
• 溶解度：
  可溶于氯仿、二甲基亚砜

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  55.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 包装等级：
  II
• 危险类别：
  6.1,8
• 危险性防范说明：
  P260,P264,P270,P271,P280,P301+P330+P331,P302+P352,P303+P361+P353,P304+P340,P305+P351+P338,P310,P403+P233,P405,P501
• 危险品运输编号：
  2928
• 危险性描述：
  H301,H311,H314,H331
• 储存条件：
  | 温度 | 存储条件 | | --- | --- | | 2-8°C | 惰性气体 |

反应信息

• 作为反应物：
  描述：

  1,4-二氯-7-异喹啉磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 17.0h， 生成 Cyclic deriv. 32
  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-1,4-二氯异喹啉 在 正丁基锂 、 磺酰氯 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 为溶剂， 反应 4.58h， 生成 1,4-二氯-7-异喹啉磺酰氯
  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

• 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)的化合物及其药用盐，其中R1和R2中的一个是H，另一个是NHC(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
  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.

  公开了式(I)的异喹啉基胍化合物：##STR1##其中取代基如本文所定义，并公开了其盐，作为尿激酶抑制剂。
• 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。
• [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：EP1077945B1

  公开（公告）日：2003-01-08