{[4-(3-bromo-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester | 631903-29-2

• 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-(3-bromo-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[4-(3-bromophenyl)sulfonyl-5-methylsulfanylthiophene-2-carboximidoyl]carbamate
• CAS: 631903-29-2
• 化学式: C₁₇H₁₉BrN₂O₄S₃
• 分子量: 491.451
• InChiKey: AOUMAODPLMTFCM-UHFFFAOYSA-N

物化性质

• 密度：
  1.54±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  161
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  {[4-(3-bromo-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester 在 isopropyl magnesium chloride 、 正丁基锂 、 硼酸三甲酯 作用下， 以 四氢呋喃 、 hexanes 为溶剂， 反应 0.41h， 以95%的产率得到{[4-(3-dihydroxyboranyl-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  [EN] NOVEL THIOPHENE AMIDINES, COMPOSITIONS THEREOF, AND METHODS OF TREATING COMPLEMENT-MEDIATED DISEASES AND CONDITIONS
  [FR] NOUVELLES AMIDINES DE THIOPHENE, COMPOSITIONS DE CES AMIDINES ET PROCEDE POUR TRAITER DES MALADIES ET DES ETATS MEDIES PAR LE COMPLEMENT

  摘要：

  揭示了一种治疗急性或慢性疾病症状的方法，该方法通过补体级联的经典途径介导，包括向需要此类治疗的哺乳动物施用化合物I的治疗有效量或其溶剂化合物、水合物或药用可接受盐；其中规范中定义了R1、R2、R3、R4和R7，Z为SO或SO2，Ar为本规范中定义的芳香族或杂环芳基。

  公开号：

  WO2003099805A1
• 作为产物：
  描述：

  4-(3-Bromo-benzenesulfonyl)-5-methylsulfanyl-thiophene-2-carboxamidine 、 二碳酸二叔丁酯 以 四氢呋喃 为溶剂， 生成 {[4-(3-bromo-benzenesulfonyl)-5-methylsulfanyl-thiophen-2-yl]-imino-methyl}-carbamic acid tert-butyl ester
  参考文献：
  名称：

  Biphenylsulfonyl-thiophene-carboxamidine inhibitors of the complement component C1s

  摘要：

  Complement activation has been implicated in disease states such as hereditary angioedema, ischemia-reperfusion injury, acute respiratory distress syndrome, and acute transplant rejection. Even though the complement cascade provides several protein targets for potential therapeutic intervention only two complement inhibitors have been approved so far for clinical use including anti-C5 antibodies for the treatment of paroxysmal nocturnal hemoglobinuria and purified C1-esterase inhibitor replacement therapy for the control of hereditary angioedema flares. In the present study, optimization of potency and physicochemical properties of a series of thiophene amidine-based C1s inhibitors with potential utility as intravenous agents for the inhibition of the classical pathway of complement is described. (c) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.01.064

文献信息

• Novel thiophene amidines, compositions thereof, and methods of treating complement-mediated diseases and conditions
  申请人：3-Dimensional Pharmaceuticals, Inc.

  公开号：US20040009995A1

  公开（公告）日：2004-01-15

  Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula I 1 or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R 1 , R 2 , R 3 , R 4 and R 7 are defined in the specification, Z is SO or SO 2 , and Ar is an aromatic or heteroaromatic group as defined herein.

  揭示了一种治疗急性或慢性疾病症状的方法，该方法通过补体级联的经典途径介导，包括向需要此类治疗的哺乳动物施用公式I的化合物的治疗有效量或其溶剂化合物、水合物或药用可接受盐；其中在规范中定义了R1、R2、R3、R4和R7，Z为SO或SO2，Ar为本文中定义的芳香族或杂环芳基。
• Conjugated complement cascade inhibitors
  申请人：Subasinghe Nalin

  公开号：US20050004031A1

  公开（公告）日：2005-01-06

  The present invention is directed to conjugated complement cascade inhibitors, and a method of treating a patient using a conjugated complement cascade inhibitor.

  本发明涉及共轭的补体级联抑制剂，以及使用共轭的补体级联抑制剂治疗患者的方法。
• Thiophene amidines, compositions thereof, and methods of treating complement-mediated diseases and conditions
  申请人：3-Dimensional Pharmaceuticals, Inc.

  公开号：US07138530B2

  公开（公告）日：2006-11-21

  Disclosed is a method for treating the symptoms of an acute or chronic disorder mediated by the classical pathway of the complement cascade, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of Formula (I) or a solvate, hydrate or pharmaceutically acceptable salt thereof; wherein R1, R2, R3, R4 and R7 are defined in the specification, Z is SO or SO2, and Ar is an aromatic or heteroaromatic group as defined herein.

  本发明揭示了一种治疗由补体级联反应的经典途径介导的急性或慢性疾病症状的方法，包括向需要此类治疗的哺乳动物施用公式（I）的化合物或其溶剂化物、水合物或药学上可接受的盐的治疗有效量；其中R1、R2、R3、R4和R7在规范中有定义，Z为SO或SO2，Ar为芳香或杂芳基，如规范中所定义。
• Design and synthesis of polyethylene glycol-modified biphenylsulfonyl-thiophene-carboxamidine inhibitors of the complement component C1s
  作者：Nalin L. Subasinghe、Ehab Khalil、Jeremy M. Travins、Farah Ali、Shelley K. Ballentine、Heather R. Hufnagel、Wenxi Pan、Kristi Leonard、Roger F. Bone、Richard M. Soll、Carl S. Crysler、Nisha Ninan、Jennifer Kirkpatrick、Michael X. Kolpak、Karen A. Diloreto、Stephen H. Eisennagel、Norman D. Huebert、Christopher J. Molloy、Bruce E. Tomczuk、Michael D. Gaul

  DOI：10.1016/j.bmcl.2012.06.030

  日期：2012.8

  Complement C1s protease inhibitors have potential utility in the treatment of diseases associated with activation of the classical complement pathway such as humorally mediated graft rejection, ischemia-reperfusion injury (IRI), vascular leak syndrome, and acute respiratory distress syndrome (ARDS). The utility of biphenylsulfonyl-thiophene-carboxamidine small-molecule C1s inhibitors are limited by their poor in vivo pharmacokinetic properties. Pegylation of a potent analog has provided compounds with good potency and good in vivo pharmacokinetic properties. (C) 2012 Elsevier Ltd. All rights reserved.
• NOVEL THIOPHENE AMIDINES, COMPOSITIONS THEREOF, AND METHODS OF TREATING COMPLEMENT-MEDIATED DISEASES AND CONDITIONS
  申请人：3-DIMENSIONAL PHARMACEUTICALS, INC.

  公开号：EP1549632A1

  公开（公告）日：2005-07-06