tert-butyl 2-amino-4-(propan-2-yl)thiophene-3-carboxylate | 207743-70-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩类
• 英文名称: tert-butyl 2-amino-4-(propan-2-yl)thiophene-3-carboxylate
• 英文别名: tert-butyl 2-amino-4-isopropylthiophene-3-carboxylate；tert-butyl 2-amino-4-propan-2-ylthiophene-3-carboxylate
• CAS: 207743-70-2
• 化学式: C₁₂H₁₉NO₂S
• 分子量: 241.354
• InChiKey: ZRHHZVCYOOCZFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  80.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  tert-butyl 2-amino-4-(propan-2-yl)thiophene-3-carboxylate 在 三氟乙酸 、 三氟乙酸酐 作用下， 以 乙醇 为溶剂， 反应 2.0h， 生成 2-Ethoxy-5-isopropyl-thieno[2,3-d][1,3]oxazin-4-one
  参考文献：
  名称：

  Novel Thieno[2,3-d][1,3]oxazin-4-ones as Inhibitors of Human Leukocyte Elastase

  摘要：

  A series of thieno[2,3-d][1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase. New synthetic routes to 2-alkoxy-, 2-alkylthio-, and 2-sec-amino-substituted derivatives are reported. This study demonstrates the versatility of 2-aminothiophenes prepared by Gewald reaction as a synthetic entry to serine protease-inhibiting, fused 1,3-oxazin-4-ones. Introduction of ethoxy, n-propoxy, and ethylthio groups at C-2 delivered the most potent inhibitors of this series with K-i values lower than 11 nM. Kinetic studies and product analyses revealed the formation of acyl-enzymes as a result of the attack of the active site serine at the carbon C-4 and subsequent deacylation. This mode of action is similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. Replacement of the benzene ring in benzoxazinones by a (substituted) thiophene led to improved hydrolytic stability and retained inhibitory potency.

  DOI：

  10.1021/jm9708341
• 作为产物：
  描述：

  在 sulfur 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.25h， 以53%的产率得到tert-butyl 2-amino-4-(propan-2-yl)thiophene-3-carboxylate
  参考文献：
  名称：

  Novel Thieno[2,3-d][1,3]oxazin-4-ones as Inhibitors of Human Leukocyte Elastase

  摘要：

  A series of thieno[2,3-d][1,3]oxazin-4-ones was synthesized and evaluated in vitro for inhibitory activity toward human leukocyte elastase. New synthetic routes to 2-alkoxy-, 2-alkylthio-, and 2-sec-amino-substituted derivatives are reported. This study demonstrates the versatility of 2-aminothiophenes prepared by Gewald reaction as a synthetic entry to serine protease-inhibiting, fused 1,3-oxazin-4-ones. Introduction of ethoxy, n-propoxy, and ethylthio groups at C-2 delivered the most potent inhibitors of this series with K-i values lower than 11 nM. Kinetic studies and product analyses revealed the formation of acyl-enzymes as a result of the attack of the active site serine at the carbon C-4 and subsequent deacylation. This mode of action is similar to the inhibition of serine proteases by 4H-3,1-benzoxazin-4-ones. Replacement of the benzene ring in benzoxazinones by a (substituted) thiophene led to improved hydrolytic stability and retained inhibitory potency.

  DOI：

  10.1021/jm9708341

文献信息

• PLASMINOGEN ACTIVATOR INHIBITOR-1 INHIBITOR
  申请人：Miyata Toshio

  公开号：US20090124620A1

  公开（公告）日：2009-05-14

  The present invention relates to an inhibitor of plasminogen activator inhibitor-1. The present invention further relates to a pharmaceutical composition that has an inhibitory action on PAI-1 activity and is useful in the prevention and treatment of various diseases whose onset is associated with PAI-1 activity. Furthermore, the present invention relates to a novel compound having PAI-1 inhibitory activity represented by the following general formula (I), and a salt thereof. Each symbol is defined as those in the specification.

  本发明涉及一种抑制纤溶酶原激活物抑制剂-1的抑制剂。本发明进一步涉及一种对PAI-1活性具有抑制作用的药物组合物，可用于预防和治疗与PAI-1活性相关的各种疾病的发生。此外，本发明涉及一种具有PAI-1抑制活性的新化合物，其由以下一般式（I）表示，并且其盐。每个符号的定义如规范中所述。
• Structure-Activity Relationships of New 2-Acylamino-3-thiophenecarboxylic Acid Dimers as Plasminogen Activator Inhibitor-1 Inhibitors
  作者：Nagahisa Yamaoka、Yasuhiko Kawano、Yuko Izuhara、Toshio Miyata、Kanji Meguro

  DOI：10.1248/cpb.58.615

  日期：——

  Small molecule inhibitors of plasminogen activator inhibitor (PAI)-1 have been reported to date but their clinical effects still remain unknown. The present study was undertaken to investigate the structure–activity relationships (SAR) of newly synthesized 2-acylamino-3-thiophenecarboxylic acid dimers based upon a core structure of TM5001 (1) and TM5007 (2) that we have previously identified as orally effective PAI-1 inhibitors. In general, compounds possessing bulky or/and hydrophobic substituents (e.g. phenyl, isobutyl group) on the both thiophene rings showed potent PAI-1 inhibitory activities irrespective of the positions of the substitution. The mono-carboxyl derivative (10) exhibited PAI-1 inhibition comparable to the corresponding dicarboxyl compound (9f).

  迄今为止，纤溶酶原激活物抑制剂（PAI）-1 的小分子抑制剂已有报道，但其临床效果仍然未知。本研究以 TM5001 (1) 和 TM5007 (2) 的核心结构为基础，研究了新合成的 2-酰氨基-3-噻吩羧酸二聚体的结构-活性关系（SAR）。一般来说，在两个噻吩环上都具有笨重或/和疏水取代基（如苯基、异丁基）的化合物，无论取代基的位置如何，都具有很强的 PAI-1 抑制活性。单羧基衍生物（10）对 PAI-1 的抑制作用与相应的二羧基化合物（9f）相当。
• THIOPHENS AND THEIR USE AS ANTI-TUMOR AGENTS
  申请人：Compass Pharmaceuticals LLC

  公开号：EP1802634A2

  公开（公告）日：2007-07-04
• Thiophens and Their Use as Anti-Tumor Agents
  申请人：Ward John

  公开号：US20090143411A1

  公开（公告）日：2009-06-04

  The present invention provides novel compounds and pharmaceutical compositions thereof, as well as methods for using the compounds and pharmaceutical compositions for treating tumors. Examples of specific tumor types that the compounds may be used to treat include, but are not limited to sarcomas, melanomas, neuroblastomas, carcinomas (including but not limited to lung, renal cell, ovarian, liver, bladder, and pancreatic carcinomas), and mesotheliomas.
• US7951806B2
  申请人：——

  公开号：US7951806B2

  公开（公告）日：2011-05-31