N,N-dimethyl-2-hydroxy-2-(4-benzyloxy)phenylthioacetamide | 193965-54-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: N,N-dimethyl-2-hydroxy-2-(4-benzyloxy)phenylthioacetamide
• 英文别名: α-(4-benzyloxyphenyl)-α-hydroxy-N,N-dimethylthioacetamide；alpha-(4-Benzyloxyphenyl)-alpha-hydroxy-N,N-dimethyl-thioacetamide；2-hydroxy-N,N-dimethyl-2-(4-phenylmethoxyphenyl)ethanethioamide
• CAS: 193965-54-7
• 化学式: C₁₇H₁₉NO₂S
• 分子量: 301.409
• InChiKey: UQYCQNOWECYYPH-UHFFFAOYSA-N

物化性质

• 沸点：
  456.9±55.0 °C(Predicted)
• 密度：
  1.203±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  64.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N,N-dimethyl-2-hydroxy-2-(4-benzyloxy)phenylthioacetamide 在 正丁基锂 、 甲烷磺酸 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 氯苯 为溶剂， 反应 10.75h， 生成 6-Benzyloxy-2-[6-[2-(1-pyrrolidinyl)ethoxy]pyrid-3-yl]benzo[b]thiophen-3-yl 3-Methoxy-4-[(1-pyrrolidinyl)methyl]phenyl Ketone
  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-苄氧基苯甲醛 、 N,N-二甲基硫代甲酰胺 在 正丁基锂 、 二异丙胺 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 以20.0 g (66.5 mmol, 46%)的产率得到N,N-dimethyl-2-hydroxy-2-(4-benzyloxy)phenylthioacetamide
  参考文献：
  名称：

  Antithrombotic agents

  摘要：

  这个应用涉及到公式I的新化合物（及其药用盐），如本文所定义，用于它们的制备的过程和中间体，包含公式I的新化合物的药物配方，以及将公式I的化合物用作凝血酶抑制剂。

  公开号：

  US06284756B1

文献信息

• Antithrombotic agents
  申请人：Eli Lilly And Company

  公开号：US06350774B1

  公开（公告）日：2002-02-26

  This application relates to novel compounds of formula (I) (and their pharmaceutically acceptable salts), as defined herein, processes and intermediates for their preparation, pharmaceutical formulations comprising the novel compounds of formula (I), and the use of the compounds of formula (I) as thrombin inhibitors.

  这项申请涉及到式(I)的新化合物（及其药用可接受的盐），如本文所定义，用于它们的制备的工艺和中间体，包括式(I)的新化合物的药物配方，以及将式(I)的化合物用作凝血酶抑制剂。
• Thrombin inhibitors
  申请人：Eli Lilly and Company

  公开号：US06391901B1

  公开（公告）日：2002-05-21

  This application relates to novel compounds of formula I (and their pharmaceutically acceptable salts), as defined herein, processes and intermediates for their preparation, pharmaceutical formulations comprising the novel compounds of formula I, and the use of defined compounds of formula I as thrombin inhibitors.

  这项申请涉及到式I的新化合物（及其药学上可接受的盐），如本文所定义，用于它们的制备的过程和中间体，包含式I的新化合物的药物配方，以及将式I的特定化合物用作凝血酶抑制剂。
• Antithrombotic Agents
  申请人：Eli Lilly and Company

  公开号：US06271227B1

  公开（公告）日：2001-08-07

  This application relates to novel compounds of formula (I) (and their pharmaceutically acceptable salts), as defined herein, processes and intermediates for their preparation, pharmaceutical formulations comprising the novel compounds of formula (I), and the use of the compounds of formula (I) as thrombin inhibitors.

  本申请涉及公式(I)的新化合物（以及其药学上可接受的盐），如此处所定义，用于其制备的过程和中间体，含有公式(I)新化合物的制药配方，以及化合物(I)作为凝血酶抑制剂的用途。
• [EN] ANTITHROMBOTIC DIAMINES<br/>[FR] DIAMINES ANTITHROMBOTIQUES
  申请人：ELI LILLY AND COMPANY

  公开号：WO1997025033A1

  公开（公告）日：1997-07-17

  (EN) 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).(FR) La présente invention concerne l'utilisation, comme inhibiteurs de thrombine, inhibiteurs de coagulation et agents destinés aux désordres de la thromboembolie, de diamines de formule I telle qu'elle est définie dans la description. L'invention concerne aussi des composés nouveaux de formule I, des procédés et des produits intermédiaires pour leur préparation, et des formulations pharmaceutiques comprenant les composés nouveaux de formule I.

  该应用涉及使用公式（I）所定义的二胺作为凝血酶抑制剂、凝血抑制剂和血栓栓塞疾病药物的用途。它还提供了公式（I）的新化合物、其制备过程和中间体，以及包含公式（I）的新药物配方。
• Dibasic benzo[b]thiophene derivatives as a novel class of active site directed thrombin inhibitors: 4. SAR studies on the conformationally restricted C3-side chain of hydroxybenzo[b]thiophenes
  作者：Kumiko Takeuchi、Todd J. Kohn、Daniel J. Sall、Michael L. Denney、Jefferson R. McCowan、Gerry F. Smith、Donetta S. Gifford-Moore

  DOI：10.1016/s0960-894x(99)00076-1

  日期：1999.3

  A novel series of benzo[b]thiophene diamine thrombin inhibitors with a conformationally restricted C3-side chain 3 was investigated. The constrained C3-side chain by a cyclohexyl ring contributed to not only an additive but also a synergistic effect on the thrombin inhibitory activity. The SAR studies resulted in the discovery of a potent thrombin inhibitor 27 that was over 750-fold more potent than the initial lead compound 1. (C) 1999 Elsevier Science Ltd. All rights reserved.