2-cyano-5-(3-thiophen-3-yl)methyloxybenzaldehyde | 210109-99-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-cyano-5-(3-thiophen-3-yl)methyloxybenzaldehyde
• 英文别名: 2-Formyl-4-(thiophen-3-ylmethoxy)benzonitrile
• CAS: 210109-99-2
• 化学式: C₁₃H₉NO₂S
• 分子量: 243.286
• InChiKey: SHZMESHGMPESOL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  78.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-cyano-5-(3-thiophen-3-yl)methyloxybenzaldehyde 在 dimethyl sulfide borane 、 乙酸酐 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.33h， 生成 (Z)-2-phenyl-3-[2-cyano-5-(3-thiophen-3-yl)methyloxyphenyl]propenol
  参考文献：
  名称：

  Selective Endothelin A Receptor Antagonists. 4. Discovery and Structure−Activity Relationships of Stilbene Acid and Alcohol Derivatives

  摘要：

  This publication describes the synthesis and optimization of a novel series of stilbene endothelin antagonists. Analysis of the SAR established for previous papers in this series prompted the design and synthesis of (Z)-4-phenyl-5-(3-benzyloxyphenyl)pent-4-enoic acid 3 which was found to be a moderately active inhibitor of the binding of [I-125]ET-1 to ETA receptors with an IC50 Of 6 mu M. More interestingly, the intermediate compound (E)-2-phenyl-3-(3-enzyloxyphenyl)-propenoic acid 5 was equiactive with 3. Optimization of 5 resulted in the preparation of (E)2-phenyl-3-(2-cyano-5-(thien-3-ylmethoxy))phenylpropenoic acid 18 (RPR111723) which had an IC50 in the binding assay of 80 nM on the ETA receptor and a pK(B) of 6.5 in the functional assay, measured on rat aortic strips. Reduction of the acid group of 5 gave the first nonacidic ETA antagonist in our series, (E)-2-phenyl-3-(3-benzyloxyphenoxy)prop2-enol 6 with an IC50 Of 20 mu M. Optimization of 6 resulted in the preparation of 2-(2-methylphenyl)-3-(2-cyano-5-(thien-3-ylmethyl)phenyl)prop-2-enol 33 with an IC50 Of 300 nM on the ETA receptor.

  DOI：

  10.1021/jm970847e
• 作为产物：
  描述：

  2-溴-5-羟基苯甲醛 在 potassium tert-butylate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.75h， 生成 2-cyano-5-(3-thiophen-3-yl)methyloxybenzaldehyde
  参考文献：
  名称：

  Selective Endothelin A Receptor Antagonists. 4. Discovery and Structure−Activity Relationships of Stilbene Acid and Alcohol Derivatives

  摘要：

  This publication describes the synthesis and optimization of a novel series of stilbene endothelin antagonists. Analysis of the SAR established for previous papers in this series prompted the design and synthesis of (Z)-4-phenyl-5-(3-benzyloxyphenyl)pent-4-enoic acid 3 which was found to be a moderately active inhibitor of the binding of [I-125]ET-1 to ETA receptors with an IC50 Of 6 mu M. More interestingly, the intermediate compound (E)-2-phenyl-3-(3-enzyloxyphenyl)-propenoic acid 5 was equiactive with 3. Optimization of 5 resulted in the preparation of (E)2-phenyl-3-(2-cyano-5-(thien-3-ylmethoxy))phenylpropenoic acid 18 (RPR111723) which had an IC50 in the binding assay of 80 nM on the ETA receptor and a pK(B) of 6.5 in the functional assay, measured on rat aortic strips. Reduction of the acid group of 5 gave the first nonacidic ETA antagonist in our series, (E)-2-phenyl-3-(3-benzyloxyphenoxy)prop2-enol 6 with an IC50 Of 20 mu M. Optimization of 6 resulted in the preparation of 2-(2-methylphenyl)-3-(2-cyano-5-(thien-3-ylmethyl)phenyl)prop-2-enol 33 with an IC50 Of 300 nM on the ETA receptor.

  DOI：

  10.1021/jm970847e

文献信息

• Selective Endothelin A Receptor Antagonists. 4. Discovery and Structure−Activity Relationships of Stilbene Acid and Alcohol Derivatives
  作者：Peter C. Astles、Thomas J. Brown、Frank Halley、Caroline M. Handscombe、Neil V. Harris、Clive McCarthy、Iain M. McLay、Peter Lockey、Tahir Majid、Barry Porter、Alan G. Roach、Christopher Smith、Roger Walsh

  DOI：10.1021/jm970847e

  日期：1998.7.1

  This publication describes the synthesis and optimization of a novel series of stilbene endothelin antagonists. Analysis of the SAR established for previous papers in this series prompted the design and synthesis of (Z)-4-phenyl-5-(3-benzyloxyphenyl)pent-4-enoic acid 3 which was found to be a moderately active inhibitor of the binding of [I-125]ET-1 to ETA receptors with an IC50 Of 6 mu M. More interestingly, the intermediate compound (E)-2-phenyl-3-(3-enzyloxyphenyl)-propenoic acid 5 was equiactive with 3. Optimization of 5 resulted in the preparation of (E)2-phenyl-3-(2-cyano-5-(thien-3-ylmethoxy))phenylpropenoic acid 18 (RPR111723) which had an IC50 in the binding assay of 80 nM on the ETA receptor and a pK(B) of 6.5 in the functional assay, measured on rat aortic strips. Reduction of the acid group of 5 gave the first nonacidic ETA antagonist in our series, (E)-2-phenyl-3-(3-benzyloxyphenoxy)prop2-enol 6 with an IC50 Of 20 mu M. Optimization of 6 resulted in the preparation of 2-(2-methylphenyl)-3-(2-cyano-5-(thien-3-ylmethyl)phenyl)prop-2-enol 33 with an IC50 Of 300 nM on the ETA receptor.