ethyl 2-[(2-fluorophenyl)amino]-1,3-thiazole-4-carboxylate | 1366234-05-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: ethyl 2-[(2-fluorophenyl)amino]-1,3-thiazole-4-carboxylate
• 英文别名: ethyl 2-((2-fluorophenyl)amino)thiazole-4-carboxylate；Ethyl 2-[(2-fluorophenyl)amino]-1,3-thiazole-4-carboxylate；ethyl 2-(2-fluoroanilino)-1,3-thiazole-4-carboxylate
• CAS: 1366234-05-0
• 化学式: C₁₂H₁₁FN₂O₂S
• mdl: MFCD22578257
• 分子量: 266.296
• InChiKey: MUUPMPAQDGALQX-UHFFFAOYSA-N

物化性质

• 沸点：
  374.4±48.0 °C(Predicted)
• 密度：
  1.353±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  79.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 2-[(2-fluorophenyl)amino]-1,3-thiazole-4-carboxylate 在 sodium hydroxide 、 盐酸 作用下， 以 乙醇 、 水 为溶剂， 生成 2-[(2-fluorophenyl)amino]-1,3-thiazole-4-carboxylic acid
  参考文献：
  名称：

  [EN] COMPOUNDS
  [FR] COMPOSÉS

  摘要：

  化合物，含有它们的制药组合物，以及它们用于治疗由TRPC3和/或TRPC6离子通道介导的疾病的用途。

  公开号：

  WO2012037351A1
• 作为产物：
  描述：

  3-溴丙酮酸乙酯 、 1-(2-氟苯基)-2-硫脲 以 乙醇 为溶剂， 生成 ethyl 2-[(2-fluorophenyl)amino]-1,3-thiazole-4-carboxylate
  参考文献：
  名称：

  [EN] COMPOUNDS
  [FR] COMPOSÉS

  摘要：

  化合物，含有它们的制药组合物，以及它们用于治疗由TRPC3和/或TRPC6离子通道介导的疾病的用途。

  公开号：

  WO2012037351A1

文献信息

• Ethyl 2-((4-Chlorophenyl)amino)thiazole-4-carboxylate and Derivatives Are Potent Inducers of Oct3/4
  作者：Xinlai Cheng、Hiroki Yoshida、Dena Raoofi、Sawsan Saleh、Hamed Alborzinia、Frank Wenke、Axel Göhring、Stefanie Reuter、Nancy Mah、Heiko Fuchs、Miguel A. Andrade-Navarro、James Adjaye、Sheraz Gul、Jochen Utikal、Ralf Mrowka、Stefan Wölfl

  DOI：10.1021/acs.jmedchem.5b00226

  日期：2015.8.13

  The octamer-binding transcription factor 4 (Oct3/4) is a master gene in the transcriptional regulatory network of pluripotent cells. Repression of Oct3/4 in embryonic stem cells (ESCs) is associated with cell differentiation and loss of pluripotency, whereas forced overexpression in cooperation with other transcriptional factors, such as Nanog, Sox2, and Lin28, can reprogram somatic cells back into pluripotent cells, termed induced pluripotent stem cells (iPSCs). However, random integration and potential tumorigenic transformation caused by viral transduction limit the clinical application of iPSCs. By performing a cell-based high throughput screening (HTS) campaign, we identified several potential small molecules as inducers of Oct3/4 expression. Here we report a lead structure ethyl 2-((4-chlorophenyl)amino)- thiazole-4-carboxylate, termed O4I2, showing high activity in enforcing Oct3/4 expression. On the basis of chemical expansion, we further identified derivatives having increased activities toward Oct3/4 induction. Thus, O4I2 and its derivatives should provide a new class of small molecules suitable for iPSC generation.
• The discovery of potent blockers of the canonical transient receptor channels, TRPC3 and TRPC6, based on an anilino-thiazole pharmacophore
  作者：David G. Washburn、Dennis A. Holt、Jason Dodson、Jeff J. McAtee、Lamont R. Terrell、Linda Barton、Sharada Manns、Anna Waszkiewicz、Christina Pritchard、Dan J. Gillie、Dwight M. Morrow、Elizabeth A. Davenport、Irina M. Lozinskaya、Jeffrey Guss、Jonathan B. Basilla、Lorena Kallal Negron、Michael Klein、Robert N. Willette、Rusty E. Fries、Timothy C. Jensen、Xiaoping Xu、Christine G. Schnackenberg、Joseph P. Marino

  DOI：10.1016/j.bmcl.2013.06.047

  日期：2013.9

  Lead optimization of piperidine amide HTS hits, based on an anilino-thiazole core, led to the identification of analogs which displayed low nanomolar blocking activity at the canonical transient receptor channels 3 and 6 (TRPC3 & 6) based on FLIPR (carbachol stimulated) and electrophysiology (OAG stimulated) assays. In addition, the anilino-thiazole amides displayed good selectivity over other TRP channels (TRPA1, TRPV1, and TRPV4), as well as against cardiac ion channels (CaV1.2, hERG, and NaV1.5). The high oxidation potential of the aliphatic piperidine and aniline groups, as well as the lability of the thiazole amide group contributed to the high clearance observed for this class of compounds. Conversion of an isoquinoline amide to a naphthyridine amide markedly reduced clearance for the bicyclic piperidines, and improved oral bioavailability for this compound series, however TRPC3 and TRPC6 blocking activity was reduced substantially. Although the most potent anilino-thiazole amides ultimately lacked oral exposure in rodents and were not suitable for chronic dosing, analogs such as 14-19, 22, and 23 are potentially valuable in vitro tool compounds for investigating the role of TRPC3 and TRPC6 in cardiovascular disease. Published by Elsevier Ltd.