trans,trans-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-(N-[2,3-dimethylphenyl]acetamido)-pyrrolidino-3-carboxylic acid

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: trans,trans-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-(N-[2,3-dimethylphenyl]acetamido)-pyrrolidino-3-carboxylic acid
• 英文别名: (2R,3R,4S)-4-Benzo[1,3]dioxol-5-yl-1-[(2,3-dimethyl-phenylcarbamoyl)-methyl]-2-(4-methoxy-phenyl)-pyrrolidine-3-carboxylic acid；(2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-(2,3-dimethylanilino)-2-oxoethyl]-2-(4-methoxyphenyl)pyrrolidine-3-carboxylic acid
• 化学式: C₂₉H₃₀N₂O₆
• 分子量: 502.567
• InChiKey: UHXUKJPNFOYGKB-OFEZKSIWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  37
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  97.3
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2,3-二甲基苯胺 在 sodium hydroxide 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 1.5h， 生成 trans,trans-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-(N-[2,3-dimethylphenyl]acetamido)-pyrrolidino-3-carboxylic acid
  参考文献：
  名称：

  Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 4. Side Chain Conformational Restriction Leads to ET_B Selectivity

  摘要：

  When the dialkylacetamide side chain of the ETA-selective antagonist ABT-627 is replaced with a 2,6-dialkylacetanilide, the resultant analogues show a complete reversal of receptor selectivity, preferring ETB over ETA. By optimizing the aniline substitution pattern, as well as the alkoxy group on the 2-aryl substituent, it is possible to prepare antagonists with subnanomolar affinity for ETB and with selectivities in excess of 4000-fold. A number of these compounds also show promising pharmacokinetic profiles; a useful balance of properties is found in A-192621 (38). Pharmacology studies with A-192621 serve to reveal the role of the ETB receptor in modulating blood pressure; the observed hypertensive response to persistent ETB blockade is consistent with previous postulates and indicates that ETB-selective antagonists may not be suitable as agents for long-term systemic therapy.

  DOI：

  10.1021/jm990170q