dimethyl 2-[(Z)-3-[2-cyano-5-(thiophen-3-ylmethoxy)phenyl]-2-phenylprop-2-enyl]propanedioate | 1027081-49-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: dimethyl 2-[(Z)-3-[2-cyano-5-(thiophen-3-ylmethoxy)phenyl]-2-phenylprop-2-enyl]propanedioate
• CAS: 1027081-49-7
• 化学式: C₂₆H₂₃NO₅S
• 分子量: 461.538
• InChiKey: BWUMFOAPZYQKQM-UUYOSTAYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  114
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  dimethyl 2-[(Z)-3-[2-cyano-5-(thiophen-3-ylmethoxy)phenyl]-2-phenylprop-2-enyl]propanedioate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 5.17h， 生成 (Z)-4-phenyl-5-[2-cyano-5-(thiophen-3-ylmethoxy)phenyl]penten-4-oic acid
  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-cyano-5-(3-thiophen-3-yl)methyloxybenzaldehyde 在 四溴化碳 、 dimethyl sulfide borane 、 sodium methylate 、 乙酸酐 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 8.58h， 生成 dimethyl 2-[(Z)-3-[2-cyano-5-(thiophen-3-ylmethoxy)phenyl]-2-phenylprop-2-enyl]propanedioate
  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