2-[4-(2-pyrrolidinoethoxy)phenyl]-3-[4-(2-pyrrolidinoethoxy)benzoyl]benzothiophene | 63712-60-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[4-(2-pyrrolidinoethoxy)phenyl]-3-[4-(2-pyrrolidinoethoxy)benzoyl]benzothiophene
• 英文别名: 2-[4-(2-pyrrolidinoethoxy)phenyl]-3-[4-(2-pyrrolidinoethoxy)benzoyl]-benzo[b]thiophene；2-[4-[2-(1-Pyrrolidinyl)ethoxy]phenyl]benzo[b]thiophen-3-yl 4-[2-(1-pyrrolidinyl)ethoxy]phenyl ketone；[4-(2-pyrrolidin-1-ylethoxy)phenyl]-[2-[4-(2-pyrrolidin-1-ylethoxy)phenyl]-1-benzothiophen-3-yl]methanone
• CAS: 63712-60-7
• 化学式: C₃₃H₃₆N₂O₃S
• 分子量: 540.726
• InChiKey: UHKHNEASGWWACL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  39
• 可旋转键数：
  11
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  70.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-[4-(2-pyrrolidinoethoxy)phenyl]-3-[4-(2-pyrrolidinoethoxy)benzoyl]benzothiophene 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 生成 [4-(2-Pyrrolidin-1-yl-ethoxy)-phenyl]-{2-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-benzo[b]thiophen-3-yl}-methanol
  参考文献：
  名称：

  Diamino Benzo[b]thiophene Derivatives as a Novel Class of Active Site Directed Thrombin Inhibitors. 5. Potency, Efficacy, and Pharmacokinetic Properties of Modified C-3 Side Chain Derivatives

  摘要：

  A systematic investigation of the structure-activity relationships of the C-3 side chain of the screening hit la led to the identification of the potent thrombin inhibitors 23c, 28c, and 31c. Their activities (1240, 903, and 1271 x 10(6) L/mol, respectively) represent 2200- and 2900-fold increases in potency over the starting lead la. This activity enhancement was accomplished with an increase of thrombin selectivity. The in vitro anticoagulant profiles of derivatives 28c and 31c were determined, and they compare favorably with the clinical agent H-R-1-[4aS,-8aS]perhydroisoquinolyl-prolyl-arginyl aldehyde (D-Piq-Pro-Arg-H; 32). The more potent members of this series have been studied in an arterial/venous shunt (AV shunt) model of thrombosis and were found to be efficacious in reducing clot formation. However, their efficacy is currently limited by their rapid and extensive distribution following administration.

  DOI：

  10.1021/jm9903388
• 作为产物：
  描述：

  4-(2-吡咯烷-1-基乙氧基)苯甲酸 在 三氯化铝 、 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 7.0h， 生成 2-[4-(2-pyrrolidinoethoxy)phenyl]-3-[4-(2-pyrrolidinoethoxy)benzoyl]benzothiophene
  参考文献：
  名称：

  Diamino Benzo[b]thiophene Derivatives as a Novel Class of Active Site Directed Thrombin Inhibitors. 5. Potency, Efficacy, and Pharmacokinetic Properties of Modified C-3 Side Chain Derivatives

  摘要：

  A systematic investigation of the structure-activity relationships of the C-3 side chain of the screening hit la led to the identification of the potent thrombin inhibitors 23c, 28c, and 31c. Their activities (1240, 903, and 1271 x 10(6) L/mol, respectively) represent 2200- and 2900-fold increases in potency over the starting lead la. This activity enhancement was accomplished with an increase of thrombin selectivity. The in vitro anticoagulant profiles of derivatives 28c and 31c were determined, and they compare favorably with the clinical agent H-R-1-[4aS,-8aS]perhydroisoquinolyl-prolyl-arginyl aldehyde (D-Piq-Pro-Arg-H; 32). The more potent members of this series have been studied in an arterial/venous shunt (AV shunt) model of thrombosis and were found to be efficacious in reducing clot formation. However, their efficacy is currently limited by their rapid and extensive distribution following administration.

  DOI：

  10.1021/jm9903388

文献信息

• Antithrombotic diamines
  申请人：Eli Lilly and Company

  公开号：US06265575B1

  公开（公告）日：2001-07-24

  This application relates to the use as thrombin inhibitors, coagulation inhibitors and thromboembolic disorder agents of diamines of formula I as defined herein. It also provides novel compounds of formula I, processes and intermediates for their preparation, and pharmaceutical formulations comprising the novel compounds of formula I.

  本申请涉及使用式I所定义的二胺作为凝血酶抑制剂、凝血抑制剂和血栓性疾病药物的用途。它还提供了式I的新化合物、其制备的过程和中间体，以及包含式I的新药物制剂。
• ANTITHROMBOTIC DIAMINES
  申请人：ELI LILLY AND COMPANY

  公开号：EP0863755B1

  公开（公告）日：2004-12-15
• US4133814A
  申请人：——

  公开号：US4133814A

  公开（公告）日：1979-01-09
• US6025382A
  申请人：——

  公开号：US6025382A

  公开（公告）日：2000-02-15
• US6251921B1
  申请人：——

  公开号：US6251921B1

  公开（公告）日：2001-06-26