4-phenylbenzo[b]thiophene-2-carboxamidine hydrochloride

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻吩类
• 英文名称: 4-phenylbenzo[b]thiophene-2-carboxamidine hydrochloride
• 英文别名: 4-Phenyl-1-benzothiophene-2-carboximidamide;hydrochloride
• 化学式: C₁₅H₁₂N₂S*ClH
• 分子量: 288.801
• InChiKey: ISRQHYNMNRMYAR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.27
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  78.1
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  在 lithium hexamethyldisilazane 、 甲醇 、 盐酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 生成 4-phenylbenzo[b]thiophene-2-carboxamidine hydrochloride
  参考文献：
  名称：

  Studies of Benzothiophene Template as Potent Factor IXa (FIXa) Inhibitors in Thrombosis

  摘要：

  FIXa is a serine protease enzyme involved in the intrinsic pathway of the coagulation cascade. The upstream intervention of the coagulation cascade in selectively inhibiting FIXa would leave hemostasis Intact via the extrinsic pathway, leading to an optimum combination of efficacy and safety with low incidence of bleeding. We have identified 2-amindinobenzothiophene template as a lead scaffold for FIXa inhibiton based on its homology with urokinase plasminogen activator (uPA). Subsequent SAR work oil the template revealed a number of highly potent FIXa inhibitors, though with moderate selectivity against FXa. X-ray Study with one of the analogues demonstrated active site binding interaction with the induced opening of the S1 beta pocket and a secondary binding at the S2-S4 sites, which is ill direct contrast with the previous finding.

  DOI：

  10.1021/jm901475e

文献信息

• Urokinase inhibitors
  申请人：Eisai Co., Ltd.

  公开号：US05340833A1

  公开（公告）日：1994-08-23

  Disclosed are benzothiophene and thienothiophene derivatives useful for inhibiting urokinase activity.

  揭示了对抑制尿激酶活性有用的苯并噻吩和噻吩噻吩衍生物。
• Benzothiophenes and thienothiophenes and related compounds useful, for example, as urokinase inhibitors
  申请人：Eisai Co., Ltd.

  公开号：EP0568289A2

  公开（公告）日：1993-11-03

  Disclosed are benzothiophene and thienothiophene derivatives useful for inhibiting urokinase activiy. Novel components of the formula : wherein R1 is H, NH2, or a halogen ; each R2-R5, independently, is a H, halogen, hydroxy, amino, nitro or organic group, provided that at least one R2-R5 is an organic group which includes 5 carbons or greater, an organic group which contains a sulfur atom or hydroxy, an unsaturated organic group, or a cyclic organic group ; and each R6 and R7, independently, is H or a straight chain alkyl group of between 1 and 6 carbons of the formula : wherein R1 is H, NH2, or a halogen ; each R2-R5, independently, is a H, halogen, hydroxy, amino, nitro, or organic group, provided that at least one of R2-R5 is a group other than H, OH, NO2, CN, a halogen, an alkyl group of between 1 and 4 carbons, an alkoxy group of between 1 and 4 carbons, a haloalkyl group of between 1 and 4 carbons, a haloalkoxy group of between 1 and 4 carbons, an amino group, an amino group substituted with an alkyl group of between 1 and 4 carbons, a nitrile group, or a carboxamidine group, and further provided that no two adjacent R2-R5 groups together form a methylenedioxy group ; and each R6 and R7, independently, is H or a straight chain alkyl group of between 1 and 6 carbons and of the formula : wherein at least one of X, Y, or Z must be C ; at least one of X, Y, or Z must be O, N, or S ; and, if more than one of X, Y, or Z is O, N, or S, then at least one of those groups is N ; R1 is H, NH2, or a halogen ; each R2, R3, or R5, independently, is a H, halogen, or organic group ; and each R6 and R7, independently, is H or a straight chain alkyl group of between 1 and 6 carbons are described.

  公开了可用于抑制尿激酶活性的苯并噻吩和噻吩衍生物。式中的新成分......： 其中 R1 是 H、NH2 或卤素； 每个 R2-R5 分别是 H、卤素、羟基、氨基、硝基或有机基团、 但至少有一个 R2-R5 是包含 5 个碳原子或更多碳原子的有机基团、包含硫原子或羟基的有机基团、不饱和有机基团或环状有机基团；以及 每个 R6 和 R7 分别是 H 或式 1 至 6 碳原子的直链烷基： 其中 R1 是 H、NH2 或卤素； 每个 R2-R5 独立地为 H、卤素、羟基、氨基、硝基或有机基团、 条件是 R2-R5 中至少有一个是除 H、OH、NO2、CN、卤素、1-4 碳原子的烷基、1-4 碳原子的烷氧基、1-4 碳原子的卤代烷基、1-4 碳原子的卤代烷氧基以外的基团、氨基、被 1 至 4 个碳原子的烷基取代的氨基、腈基或羧酰胺基，且相邻两个 R2-R5 基团均不形成亚甲基二氧基......；且 每个 R6 和 R7 分别是 H 或 1 至 6 个碳原子的直链烷基，其式为......： 其中 X、Y 或 Z 中至少有一个必须是 C；X、Y 或 Z 中至少有一个必须是 O、N 或 S；如果 X、Y 或 Z 中不止一个是 O、N 或 S，则这些基团中至少有一个是 N； R1 是 H、NH2 或卤素； 每个 R2、R3 或 R5 分别是 H、卤素或有机基团；以及 每个 R6 和 R7 独立地为 H 或 1 至 6 个碳原子的直链烷基。
• US5340833A
  申请人：——

  公开号：US5340833A

  公开（公告）日：1994-08-23
• Studies of Benzothiophene Template as Potent Factor IXa (FIXa) Inhibitors in Thrombosis
  作者：Shouming Wang、Richard Beck、Toby Blench、Andrew Burd、Stuart Buxton、Maja Malic、Tenagne Ayele、Shaheda Shaikh、Suresh Chahwala、Chaman Chander、Richard Holland、Sandrine Merette、Lihua Zhao、Michael Blackney、Alexandra Watts

  DOI：10.1021/jm901475e

  日期：2010.2.25

  FIXa is a serine protease enzyme involved in the intrinsic pathway of the coagulation cascade. The upstream intervention of the coagulation cascade in selectively inhibiting FIXa would leave hemostasis Intact via the extrinsic pathway, leading to an optimum combination of efficacy and safety with low incidence of bleeding. We have identified 2-amindinobenzothiophene template as a lead scaffold for FIXa inhibiton based on its homology with urokinase plasminogen activator (uPA). Subsequent SAR work oil the template revealed a number of highly potent FIXa inhibitors, though with moderate selectivity against FXa. X-ray Study with one of the analogues demonstrated active site binding interaction with the induced opening of the S1 beta pocket and a secondary binding at the S2-S4 sites, which is ill direct contrast with the previous finding.