4-[4-iodophenoxy]thieno[2,3-c]pyridine-2-carboxamide | 251993-33-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[4-iodophenoxy]thieno[2,3-c]pyridine-2-carboxamide
• 英文别名: 4-(4-iodo-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid amide；4-(4-iodophenoxy)thieno[2,3-c]pyridine-2-carboxamide
• CAS: 251993-33-6
• 化学式: C₁₄H₉IN₂O₂S
• 分子量: 396.208
• InChiKey: HCFROZAECGDSEH-UHFFFAOYSA-N

物化性质

• 沸点：
  580.0±50.0 °C(Predicted)
• 密度：
  1.820±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  93.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-[4-iodophenoxy]thieno[2,3-c]pyridine-2-carboxamide 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 、 乙酸乙酯 为溶剂， 反应 6.0h， 生成 4-phenoxythieno[2,3-c]pyridine-2-carboxamide
  参考文献：
  名称：

  [EN] KINASE INHIBITORS AS THERAPEUTIC AGENTS
  [FR] INHIBITEURS DE KINASES EN TANT QU'AGENTS THERAPEUTIQUES

  摘要：

  公开号：

  WO2005110410A3
• 作为产物：
  描述：

  4-(4-iodo-phenoxy)-thieno[2,3-c]pyridine-2-carboxylic acid 在 氨 、 1-羟基苯并三唑一水物 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 4-[4-iodophenoxy]thieno[2,3-c]pyridine-2-carboxamide
  参考文献：
  名称：

  Selective Inhibition of ICAM-1 and E-Selectin Expression in Human Endothelial Cells. 2. Aryl Modifications of 4-(Aryloxy)thieno[2,3-c]pyridines with Fine-Tuning at C-2 Carbamides

  摘要：

  The elevated expression of cell adhesion molecules (CAMs) on the lumenal surface of vascular endothelial cells is a critical early event in the complex inflammatory process. The adhesive interactions of these CAMs that include E-selectin, ICAM-1, and VCAM-1 with their counterreceptors on leukocytes, such as integrins of the alpha (L)beta (2) family, result in migration of the leukocytes to the site of inflammation and cause tissue injury. Pharmaceutical agents that could suppress the induced expression of one or more of these cell adhesion molecules would provide a novel mechanism to attenuate the inflammatory responses associated with chronic inflammatory diseases. A-205804 (1), a potent and selective inhibitor of the induced expression of E-selectin and ICAM-1 over VCAM-1, was further modified with emphasis at the C-4 and C-2 positions to identify a more potent drug candidate with a good pharmacokinetic profile and physical properties. Replacement of the C-4 sulfur linkage in I with an oxygen atom eliminated one of the two major metabolites for this lead molecule. The para-position of the 4-phenoxy group of the thieno[2,3-c]pyridine lead is found to be very critical for a higher in vitro potency and selectivity of E-selectin and ICAM-1 over VCAM-1 expression. This position is presumably close to the solvent-accessible region of the target protein-inhibitor complex. An attempt to install a water-solubilizing group at the para-position of the phenoxy group to increase the aqueous solubility of this lead series through various linkages failed to provide an ideal inhibitor. Only small substituents such as fluorine are tolerated at the meta- and ortho-positions of the 4-phenoxy to retain a good in vitro potency. Bromo, trifluoromethyl, pyrazol-1-yl, and imidazol-1-yl are among the better substituents at the para-position. With fine-tuning at the C-2 position we discovered a series of very potent (IC50 < 5 nM for ICAM-1) and selective (> 200-fold vs VCAM-1) inhibitors with a good pharmacokinetic profile. Demonstrated efficacy in a rat rheumatoid arthritis model and in a mice asthma model with selected compounds is also reported.

  DOI：

  10.1021/jm0101702

文献信息

• Cell adhesion-inhibiting antiinflammatory compounds
  申请人：——

  公开号：US20010020030A1

  公开（公告）日：2001-09-06

  Compounds having Formula I 1 are useful for treating inflammation. Also disclosed are pharmaceutical compositions comprising compounds of Formula I, and methods of inhibiting/treating inflammatory diseases in a mammal.

  具有I1式的化合物对于治疗炎症有用。本文还公开了包含I式化合物的制药组合物，以及在哺乳动物中抑制/治疗炎症性疾病的方法。
• Kinase inhibitors as therapeutic agents
  申请人：Cusack Kevin

  公开号：US20060074102A1

  公开（公告）日：2006-04-06

  A compound or pharmaceutically acceptable salts thereof of Formula (I) wherein the substituents are as defined herein, which are useful as kinase inhibitors.

  式(I)化合物或其药学上可接受的盐，其中取代基如本文所定义，可用作激酶抑制剂。
• Discovery of thieno[2,3-c]pyridines as potent COT inhibitors
  作者：Dawn George、Michael Friedman、Hamish Allen、Maria Argiriadi、Claude Barberis、Agnieszka Bischoff、Anca Clabbers、Kevin Cusack、Richard Dixon、Shannon Fix-Stenzel、Thomas Gordon、Bernd Janssen、Yong Jia、Maria Moskey、Christopher Quinn、Jose-Andres Salmeron、Neil Wishart、Kevin Woller、Zhengtian Yu

  DOI：10.1016/j.bmcl.2008.08.037

  日期：2008.9

  Evaluation of hit chemotypes from high throughput screening identified a novel series of 2,4-disubstituted thieno[2,3-c]pyridines as COT kinase inhibitors. Structural modifications exploring SAR at the 2- and 4-positions resulting in inhibitors with improved enzyme potency and cellular activity are disclosed. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis and Mode of Action of ¹²⁵I- and ³H-Labeled Thieno[2,3-<i>c</i>]pyridine Antagonists of Cell Adhesion Molecule Expression
  作者：Gui-Dong Zhu、Verlyn Schaefer、Steven A. Boyd、Gregory F. Okasinski

  DOI：10.1021/jo016171j

  日期：2002.2.1

  A series of thieno[2,3-c]pyridine antagonists of cell adhesion molecule (CAM) expression, such as A-205804 (1) and A-249377 (2), selectively suppressed the induced expression of E-selectin and ICAM-1 over VCAM-1. In an effort to explore the biological mechanism of action of these inhibitors, we synthesized I-125- and H-3-labeled thieno[2,3-c]pyridines 5 and 6. An isolated diazonium tetrafluoroborate salt efficiently trapped (NaI)-I-125 on very small scale (7.5 mug of (NaI)-I-125), providing the corresponding I-125-labeled thieno[2,3-c]pyridine in modest yield. Preliminary mechanistic investigations using these radiolabeled compounds revealed that, upon incubation with human umbilical vein endothelial cells (HUVECs), these inhibitors of CAM expression translocated to the cell nucleus and were noncovalently associated with macromolecules of molecular weight greater than 650 kDa.
• CELL ADHESION-INHIBITING ANTINFLAMMATORY COMPOUNDS
  申请人：ABBOTT LABORATORIES

  公开号：EP1090009A2

  公开（公告）日：2001-04-11