2-bromo-N-(2,2-diphenylethyl)acetamide | 689271-67-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-bromo-N-(2,2-diphenylethyl)acetamide
• CAS: 689271-67-8
• 化学式: C₁₆H₁₆BrNO
• 分子量: 318.213
• InChiKey: UCTZPWXSZJHGIQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  29.1
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-bromo-N-(2,2-diphenylethyl)acetamide 在 sodium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 乙腈 为溶剂， 生成 trans,trans-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-[(2,2-diphenylethyl)aminocarbonylmethyl]pyrrolidine-3-carboxylic acid
  参考文献：
  名称：

  Design, Synthesis, and Activity of a Series of Pyrrolidine-3-carboxylic Acid-Based, Highly Specific, Orally Active ET_B Antagonists Containing a Diphenylmethylamine Acetamide Side Chain

  摘要：

  The endothelin (ET)-B receptor subtype is expressed on vascular endothelial and smooth muscle cells and mediates both vasodilation and vasoconstriction. On the basis of the pharmacophore of the previously reported ETA-specific antagonist 1, (ABT-627), we are reporting the discovery of a novel series of highly specific, orally active ETB receptor antagonists. Replacing the dibutylaminoacetamide group of 1 with a diphenylmethylaminoacetamide group resulted in antagonist 2 with a complete reversal of receptor specificity. Structure-activity relationship studies revealed that ortho-alkylation of the phenyl rings could further increase ETB affinity and also boost the ETA/ETB activity ratio of the resulting antagonists. A similar antagonism selectivity profile could also be achieved when one of the phenyl rings of the acetamide side chain was replaced with an alkyl group, preferably a tert-butyl group,(10h). Combining these features with modification of the a-aryl group of the pyrrolidine core, we have identified a potent antagonist (9k, A-308165) with over 27 000-fold selectivity favoring the ETB receptor and an acceptable pharmacokinetic profile (F = 24%) in rats.

  DOI：

  10.1021/jm990171i
• 作为产物：
  描述：

  2,2-二苯基乙胺 、 溴乙酰溴 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以74%的产率得到2-bromo-N-(2,2-diphenylethyl)acetamide
  参考文献：
  名称：

  A rotaxane mimic of the photoactive yellow protein chromophore environment: effects of hydrogen bonding and mechanical interlocking on a coumaric amide derivative

  摘要：

  研究表明，[2]轮烷中的氢键能使香豆酰胺发色团的苯酚阴离子稳定近 3 个 pKa 单位；然而，对阴离子紫外光谱偏移的影响很小，而且，考虑到PYP 的光化学特性，尽管存在氢键，阴离子轮烷中的烯烃光异构化仍受到严重抑制。

  DOI：

  10.1039/b618781a

文献信息

• A rotaxane mimic of the photoactive yellow protein chromophore environment: effects of hydrogen bonding and mechanical interlocking on a coumaric amide derivative
  作者：Jos? Bern?、Albert M. Brouwer、Sandro M. Fazio、Natalia Haraszkiewicz、David A. Leigh、Claire M. Lennon (ne? Keaveney)

  DOI：10.1039/b618781a

  日期：——

  Hydrogen bonding in a [2]rotaxane is shown to stabilise the phenolate anion of a coumaric amide chromophore by almost 3 pKa units; however, the effect on the UV spectral shift in the anion is small and, significantly given the photochemistry of PYP, despite the hydrogen bonding olefin photoisomerisation in the anionic rotaxane remains heavily suppressed.

  研究表明，[2]轮烷中的氢键能使香豆酰胺发色团的苯酚阴离子稳定近 3 个 pKa 单位；然而，对阴离子紫外光谱偏移的影响很小，而且，考虑到PYP 的光化学特性，尽管存在氢键，阴离子轮烷中的烯烃光异构化仍受到严重抑制。
• Design, Synthesis, and Activity of a Series of Pyrrolidine-3-carboxylic Acid-Based, Highly Specific, Orally Active ET_B Antagonists Containing a Diphenylmethylamine Acetamide Side Chain
  作者：Gang Liu、Natasha S. Kozmina、Martin Winn、Thomas W. von Geldern、William J. Chiou、Douglas B. Dixon、Bach Nguyen、Kennan C. Marsh、Terry J. Opgenorth

  DOI：10.1021/jm990171i

  日期：1999.9.1

  The endothelin (ET)-B receptor subtype is expressed on vascular endothelial and smooth muscle cells and mediates both vasodilation and vasoconstriction. On the basis of the pharmacophore of the previously reported ETA-specific antagonist 1, (ABT-627), we are reporting the discovery of a novel series of highly specific, orally active ETB receptor antagonists. Replacing the dibutylaminoacetamide group of 1 with a diphenylmethylaminoacetamide group resulted in antagonist 2 with a complete reversal of receptor specificity. Structure-activity relationship studies revealed that ortho-alkylation of the phenyl rings could further increase ETB affinity and also boost the ETA/ETB activity ratio of the resulting antagonists. A similar antagonism selectivity profile could also be achieved when one of the phenyl rings of the acetamide side chain was replaced with an alkyl group, preferably a tert-butyl group,(10h). Combining these features with modification of the a-aryl group of the pyrrolidine core, we have identified a potent antagonist (9k, A-308165) with over 27 000-fold selectivity favoring the ETB receptor and an acceptable pharmacokinetic profile (F = 24%) in rats.