2-(4,5-Dibromo-2-methoxycarbonylthiophen-3-yl)oxyacetic acid | 864137-66-6

• 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: 2-(4,5-Dibromo-2-methoxycarbonylthiophen-3-yl)oxyacetic acid
• CAS: 864137-66-6
• 化学式: C₈H₆Br₂O₅S
• 分子量: 374.007
• InChiKey: ZODIIMXYOMJACL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  16
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  101
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4,5-Dibromo-2-methoxycarbonylthiophen-3-yl)oxyacetic acid 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 以98%的产率得到4,5-dibromo-3-carboxymethoxy-thiophene-2-carboxylic acid
  参考文献：
  名称：

  Probing acid replacements of thiophene PTP1B inhibitors

  摘要：

  The following account describes our systematic effort to replace one of the carboxylate groups of our diacid thiophene PTP1B inhibitors. Active hits were validated using enzymatic assays before pursuing efforts to improve the potency. Only when the C2 carboxylic acid was replaced with another ionizable functional group was reversible and competitive inhibition retained. Use of a tetrazole ring or 1,2,5-thiadiazolidine-3-one-1,1-dioxide as a carboxylate mimetic led to the discovery of two unique starting series that showed improved permeability (PAMPA) and potency of the order of 300 nM. The SAR from these efforts underscores some of the major challenges in developing small molecule inhibitors for PTP1B. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.043
• 作为产物：
  描述：

  4,5-二溴-3-羟基噻吩-2-羧酸甲酯 在 potassium carbonate 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-(4,5-Dibromo-2-methoxycarbonylthiophen-3-yl)oxyacetic acid
  参考文献：
  名称：

  Probing acid replacements of thiophene PTP1B inhibitors

  摘要：

  The following account describes our systematic effort to replace one of the carboxylate groups of our diacid thiophene PTP1B inhibitors. Active hits were validated using enzymatic assays before pursuing efforts to improve the potency. Only when the C2 carboxylic acid was replaced with another ionizable functional group was reversible and competitive inhibition retained. Use of a tetrazole ring or 1,2,5-thiadiazolidine-3-one-1,1-dioxide as a carboxylate mimetic led to the discovery of two unique starting series that showed improved permeability (PAMPA) and potency of the order of 300 nM. The SAR from these efforts underscores some of the major challenges in developing small molecule inhibitors for PTP1B. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.043

文献信息

• Inhibitors of protein tyrosine phosphatase 1B
  申请人：Lee Jinbo

  公开号：US20050203087A1

  公开（公告）日：2005-09-15

  Protein tyrosine phosphatases (PTPases) such as PTP1B can play a role in regulating a wide variety of cellular responses such as insulin signaling. Substituted thiophene compounds such as, for example, 2-carboxyl, 3-carboxymethoxy, 5-aryl substituted thiophenes, can inhibit PTP1B and thereby induce greater insulin sensitivity. Accordingly, PTP1B inhibition can provide an alternate treatment for PTPase-mediated disorders such as diabetes.

  蛋白酪氨酸磷酸酶（PTPases）如PTP1B可以在调节多种细胞反应中发挥作用，例如胰岛素信号传导。取代噻吩化合物，例如2-羧基、3-羧甲氧基、5-芳基取代的噻吩，可以抑制PTP1B，从而增加胰岛素敏感性。因此，PTP1B抑制可以作为PTPase介导的疾病（如糖尿病）的替代治疗方法。
• US7521473B2
  申请人：——

  公开号：US7521473B2

  公开（公告）日：2009-04-21
• [EN] INHIBITORS OF PROTEIN TYROSINE PHOSPHATASE 1B<br/>[FR] INHIBITEURS DE LA PROTEINE TYROSINE PHOSPHATASE 1B
  申请人：WYETH CORP

  公开号：WO2005081954A2

  公开（公告）日：2005-09-09

  Protein tyrosine phosphatases (PTPases) such as PTP1B can play a role in regulating a wide variety of cellular responses such as insulin signaling. Substituted thiophene compounds such as, for example, 2-carboxyl, 3-carboxymethoxy, 5-aryl substituted thiophenes, can inhibit PTPIB and thereby induce greater insulin sensitivity. Accordingly, PTP1B inhibition can provide an alternate treatment for PTPase-mediated disorders such as diabetes.
• Probing acid replacements of thiophene PTP1B inhibitors
  作者：Zhao-Kui Wan、Bruce Follows、Steve Kirincich、Douglas Wilson、Eva Binnun、Weixin Xu、Diane Joseph-McCarthy、Junjun Wu、Michael Smith、Yan-Ling Zhang、May Tam、David Erbe、Steve Tam、Eddine Saiah、Jinbo Lee

  DOI：10.1016/j.bmcl.2007.02.043

  日期：2007.5

  The following account describes our systematic effort to replace one of the carboxylate groups of our diacid thiophene PTP1B inhibitors. Active hits were validated using enzymatic assays before pursuing efforts to improve the potency. Only when the C2 carboxylic acid was replaced with another ionizable functional group was reversible and competitive inhibition retained. Use of a tetrazole ring or 1,2,5-thiadiazolidine-3-one-1,1-dioxide as a carboxylate mimetic led to the discovery of two unique starting series that showed improved permeability (PAMPA) and potency of the order of 300 nM. The SAR from these efforts underscores some of the major challenges in developing small molecule inhibitors for PTP1B. (c) 2007 Elsevier Ltd. All rights reserved.