4'-amino-3'-bromo-N-(tert-butyl)[1,1'-biphenyl]-2-sulfonamide | 209917-94-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 4'-amino-3'-bromo-N-(tert-butyl)[1,1'-biphenyl]-2-sulfonamide
• 英文别名: 4-(2'-tert-butylaminosulfonylphenyl)-2-bromoaniline；2-(4-amino-3-bromophenyl)-N-tert-butylbenzenesulfonamide
• CAS: 209917-94-2
• 化学式: C₁₆H₁₉BrN₂O₂S
• 分子量: 383.309
• InChiKey: ZDHKRWNJWMDPDE-UHFFFAOYSA-N

物化性质

• 沸点：
  494.0±55.0 °C(Predicted)
• 密度：
  1.402±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  80.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4'-amino-3'-bromo-N-(tert-butyl)[1,1'-biphenyl]-2-sulfonamide 在 吡啶 、 三甲基铝 、 对甲苯磺酰氯 、 间氯过氧苯甲酸 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 生成 (E)-3-(1-Amino-isoquinolin-7-yl)-2-fluoro-but-2-enoic acid (3-bromo-2'-tert-butylsulfamoyl-biphenyl-4-yl)-amide
  参考文献：
  名称：

  Substituted acrylamides as factor Xa inhibitors: improving bioavailability by P1 modification

  摘要：

  To overcome the low bioavailability of our substituted acrylamide P1 benzamidine factor Xa inhibitors reported previously, neutral and less basic groups were used to replace the benzamidine. As a result, a series of P1 aminoisoquinoline substituted acrylamide Xa inhibitors was identified to be potent, selective, and orally bioavailable. Modification of P4 moiety of these compounds further improved their pharmacokinetic properties. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(02)00304-9
• 作为产物：
  描述：

  2,4-二溴苯胺 、 2-(叔丁基氨基)磺酰基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 生成 4'-amino-3'-bromo-N-(tert-butyl)[1,1'-biphenyl]-2-sulfonamide
  参考文献：
  名称：

  设计，合成和生物学评估有效和选择性的a基双环因子Xa抑制剂。

  摘要：

  血栓性疾病是死亡和发病的主要原因。Xa因子（fXa）在凝血级联反应中的正常稳态和异常血管内血栓形成的调节中起着至关重要的作用。基于分子模型研究，已经设计并合成了一系列新的fXa抑制剂，这些抑制剂在P1位置掺入了酰胺基6，5-稠合的双环部分。结构活性关系（SAR）研究已导致选择性的纳摩尔fXa抑制剂。该系列中最有效的fXa抑制剂（72，SE170）具有有效的抑制常数（K（i）= 0.3 nM），对fXa的选择性是胰蛋白酶的350倍，并且在兔动脉硬化中也显示出良好的体内功效静脉血栓形成模型（ID（50）= 0.14 micromol / kg / h）。完成了与牛胰蛋白酶复合的X射线晶体结构72

  DOI：

  10.1021/jm000113t

文献信息

• Inhibitors of factor Xa
  申请人：——

  公开号：US20020091116A1

  公开（公告）日：2002-07-11

  Novel compounds, their salts and compositions related thereto having activity against mammalian factor Xa are disclosed. The compounds are useful in vitro or in vivo for preventing or treating coagulation disorders.

  揭示了针对哺乳动物因子Xa具有活性的新化合物、它们的盐和相关组合物。这些化合物在体外或体内用于预防或治疗凝血障碍。
• Design, synthesis, and SAR of substituted acrylamides as factor Xa inhibitors
  作者：Yonghong Song、Lane Clizbe、Chhaya Bhakta、Willy Teng、Wenhao Li、Yanhong Wu、Zhaozhong Jon Jia、Penglie Zhang、Lingyan Wang、Brandon Doughan、Ting Su、James Kanter、John Woolfrey、Paul Wong、Brian Huang、Katherine Tran、Uma Sinha、Gary Park、Andrea Reed、John Malinowski、Stan Hollenbach、Robert M. Scarborough、Bing-Yan Zhu

  DOI：10.1016/s0960-894x(02)00199-3

  日期：2002.6

  Substituted acrylamides were used as templates that bridge P1 and P4 binding elements, resulting in a series of potent sub-nanomolar) and selective factor Xa inhibitors. In this template, cis-geometry of P1 and P4 ligands is highly preferred. SAR on the substituting groups, as well as on modification of P1 and P4 moieties is described. Compounds in this series show good in vivo efficacy in animal models. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Design and synthesis of factor Xa inhibitors and their prodrugs
  作者：Yonghong Song、Lane Clizbe、Chhaya Bhakta、Willy Teng、Paul Wong、Brian Huang、Katherine Tran、Uma Sinha、Gary Park、Andrea Reed、Robert M Scarborough、Bing-Yan Zhu

  DOI：10.1016/s0960-894x(02)00921-6

  日期：2003.1

  In addition to our previously reported fluoro acrylamides Xa inhibitors 2 and 3, a series of potent and novel cyclic diimide amidine compounds has been identified. In efforts to improve their oral bioavailability, replacement of the amidine group with methyl amidrazone: gives compounds of moderate potency (14, IC50 = 0.028 muM). In the amidoxime prodrug approach, the amidoxime compounds show good oral bioavailability in rats and dogs. High plasma level of prodrug 26 and significant concentration of active drug 26a were obtained upon oral administration of prodrug 26 in rats. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Design and synthesis of glycolic and mandelic acid derivatives as factor Xa inhibitors
  作者：Ting Su、Yanhong Wu、Brandon Doughan、Kim Kane-Maguire、Charles K Marlowe、James P Kanter、John Woolfrey、Brian Huang、Paul Wong、Uma Sinha、Gary Park、John Malinowski、Stan Hollenbach、Robert M Scarborough、Bing-Yan Zhu

  DOI：10.1016/s0960-894x(01)00447-4

  日期：2001.9

  A series of glycolic and mandelic acid derivatives was synthesized and investigated for their factor Xa inhibitory activity. These analogues are highly potent and selective inhibitors against fXa. In a rabbit deep vein thrombosis model, compound 26 showed significant antithrombotic effects (81% inhibition of thrombus formation) at 1.1 muM plasma concentration following intravenous administration. (C) 2001 Published by Elsevier Science Ltd.
• INHIBITORS OF FACTOR Xa
  申请人：COR THERAPEUTICS, INC.

  公开号：EP1159264A2

  公开（公告）日：2001-12-05