methyl 7-bromo-4-(4-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxylate | 313216-28-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 7-bromo-4-(4-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxylate
• CAS: 313216-28-3
• 化学式: C₁₅H₉BrClNO₃S
• 分子量: 398.664
• InChiKey: FITZHZXNBKNMQE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  76.7
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl 7-bromo-4-(4-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxylate 在 吡啶 、 copper(I) sulfate 、 氢氟酸 、 氨 、 sodium nitrite 作用下， 以 水 为溶剂， 反应 1.0h， 生成 4-(4-Chlorophenoxy)-7-fluorothieno[2,3-c]pyridine-2-carboxamide
  参考文献：
  名称：

  Development of a Potent, Specific CDK8 Kinase Inhibitor Which Phenocopies CDK8/19 Knockout Cells

  摘要：

  Beginning with promiscuous COT inhibitors, which were found to inhibit CDK8, a series of 6-aza-benzothiophene containing compounds were developed into potent, selective CDK8 inhibitors. When cocrystallized with CDK8 and cyclin C, these compounds exhibit an unusual binding mode, making a single hydrogen bond to the hinge residue A100, a second to K252, and a key cation-pi interaction with R356. Structure-based drug design resulted in tool compounds 13 and 32, which are highly potent, kinase selective, permeable compounds with a free fraction >2% and no measurable efflux. Despite these attractive properties, these compounds exhibit weak antiproliferative activity in the HCT-116 colon cancer cell line. Further examination of the activity of 32 in this cell line revealed that the compound reduced phosphorylation of the known CDK8 substrate STAT1 in a manner identical to a CDK8 knockout clone, illustrating the complex effects of inhibition of CDK8 kinase activity in proliferation in these cells.

  DOI：

  10.1021/acsmedchemlett.5b00278
• 作为产物：
  描述：

  methyl 4-(4-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxylate 在 间氯过氧苯甲酸 、 三溴氧磷 作用下， 以 二氯甲烷 为溶剂， 反应 32.0h， 生成 methyl 7-bromo-4-(4-chlorophenoxy)thieno[2,3-c]pyridine-2-carboxylate
  参考文献：
  名称：

  Development of a Potent, Specific CDK8 Kinase Inhibitor Which Phenocopies CDK8/19 Knockout Cells

  摘要：

  Beginning with promiscuous COT inhibitors, which were found to inhibit CDK8, a series of 6-aza-benzothiophene containing compounds were developed into potent, selective CDK8 inhibitors. When cocrystallized with CDK8 and cyclin C, these compounds exhibit an unusual binding mode, making a single hydrogen bond to the hinge residue A100, a second to K252, and a key cation-pi interaction with R356. Structure-based drug design resulted in tool compounds 13 and 32, which are highly potent, kinase selective, permeable compounds with a free fraction >2% and no measurable efflux. Despite these attractive properties, these compounds exhibit weak antiproliferative activity in the HCT-116 colon cancer cell line. Further examination of the activity of 32 in this cell line revealed that the compound reduced phosphorylation of the known CDK8 substrate STAT1 in a manner identical to a CDK8 knockout clone, illustrating the complex effects of inhibition of CDK8 kinase activity in proliferation in these cells.

  DOI：

  10.1021/acsmedchemlett.5b00278

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。
• A facile and general synthesis of 2,4‐Di‐ and 2,4,7‐trisubstituted thieno[2,3‐<i>c</i>]pyridines
  作者：Gui‐Dong Zhu、Indrani W. Gunawardana、Steven A. Boyd、Laura M. Melcher

  DOI：10.1002/jhet.5570450106

  日期：2008.1

  Abstractmagnified imageTreatment of 3,5‐dibromo‐ or 3,5‐dichloro‐pyridine‐4‐carboxaldehyde 2 with one equivalent of methyl thioglycolate, followed by exposure to base, provided 4‐bromo‐ or 4‐chloro‐thieno[2,3‐c]pyridine‐2‐carboxylate 4 in good yields. Oxidation of the thieno[2,3‐c]pyridine scaffold such as 7 with mCPBA, followed by treatment with POBr3, introduced a bromine exclusively at the 7‐position of the heterocycle. The 4‐ or 7‐bromide of the thienopyridines readily underwent Suzuki, Stille coupling, and Buchwald amination reactions, to afford 4‐ or 7‐substituted analogs 6 or 11. The 2‐carboxylate of 4b or 12 was smoothly removed through saponification and decarboxylation to furnish 15 or 16. Deprotonation of the thienopyridine at C‐2 position, followed by trapping with trimethyltin chloride, afforded a 2‐stannyl analog, which was readily converted to other C‐2 derivatives via Stille reaction.
• CELL ADHESION-INHIBITING ANTINFLAMMATORY COMPOUNDS
  申请人：ABBOTT LABORATORIES

  公开号：EP1090009A2

  公开（公告）日：2001-04-11
• US6232320B1
  申请人：——

  公开号：US6232320B1

  公开（公告）日：2001-05-15
• US6579882B2
  申请人：——

  公开号：US6579882B2

  公开（公告）日：2003-06-17