(2R,3R,4S)-4-Benzo[1,3]dioxol-5-yl-2-(3,4-dimethoxy-phenyl)-1-{2-[(pentane-1-sulfonyl)-propyl-amino]-ethyl}-pyrrolidine-3-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2R,3R,4S)-4-Benzo[1,3]dioxol-5-yl-2-(3,4-dimethoxy-phenyl)-1-{2-[(pentane-1-sulfonyl)-propyl-amino]-ethyl}-pyrrolidine-3-carboxylic acid
• 英文别名: (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-2-(3,4-dimethoxyphenyl)-1-[2-[pentylsulfonyl(propyl)amino]ethyl]pyrrolidine-3-carboxylic acid
• 化学式: C₃₀H₄₂N₂O₈S
• 分子量: 590.738
• InChiKey: UBMFQXBBGUCRBP-ZPJFYFFZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  41
• 可旋转键数：
  15
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  123
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  3,4-二甲氧基苯乙酮 在 Ra-Ni sodium hydroxide 、 氢气 、 sodium hydride 、 sodium cyanoborohydride 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 N,N-二异丙基乙胺 、 sodium iodide 作用下， 以 四氢呋喃 、 乙醇 、 溶剂黄146 、 异丙醇 、 乙腈 为溶剂， 反应 6.5h， 生成 (2R,3R,4S)-4-Benzo[1,3]dioxol-5-yl-2-(3,4-dimethoxy-phenyl)-1-{2-[(pentane-1-sulfonyl)-propyl-amino]-ethyl}-pyrrolidine-3-carboxylic acid
  参考文献：
  名称：

  Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 2. Sulfonamide-Based ET_A/ET_B Mixed Antagonists

  摘要：

  When the N,N-dialkylacetamide side chain of the highly ETA-selective endothelin antagonist ABT-627 (1; [2R,3R,4S]-2-(4-methoxyphenyl)-4-(1,3-benzodioxol-5-yl)-1-[[(N,N-dibutylamino)carbonyl]methyl]pyrrolidine-3-carboxylic acid; A-147627) is replaced by N,S-dialkylsulfonamidoethyl, the resultant analogs retain ETA affinity, but exhibit substantial ETB affinity as well. Structure-activity studies reveal that modifications in the length of the two alkyl groups, and in the substitution on the anisyl ring, are important in optimizing this ''balanced'' antagonist profile. In particular the combination of an N-n-propyl group, an S-alkyl chain between four and six carbons in length, and a fluorine atom ortho to the aromatic OCH3 provides compounds with sub-nanomolar affinities for both receptor subtypes, and with ETA/ETB ratios close to 1. A number of these compounds also exhibit oral bioavailabilities (in rats) in the 30-50% range and have substantial plasma half-lives. The balanced receptor-binding profile of these potent and orally bioavailable compounds complements the ETA selectivity observed with 1.

  DOI：

  10.1021/jm970101g

文献信息

• Therapeutic treatments using centhaquin
  申请人：MIDWESTERN UNIVERSITY

  公开号：US10828368B2

  公开（公告）日：2020-11-10

  Methods of treating hypertension, pain, and resuscitative hemorrhagic shock using an adrenergic agent, like centhaquin, are disclosed. The methods treat mammals, including humans.

  公开了使用肾上腺素能制剂（如仙人掌）治疗高血压、疼痛和抢救失血性休克的方法。这些方法可治疗哺乳动物，包括人类。
• METHOD AND COMPOSITION FOR TREATING DIABETIC KETOACIDOSIS
  申请人：Midwestern University

  公开号：EP2424530B1

  公开（公告）日：2015-12-16
• Method and Composition for Potentiating the Antipyretic Action of a Nonopiod Analgesic
  申请人：Gulati Anil

  公开号：US20080207763A1

  公开（公告）日：2008-08-28

  A composition and method of treating fever, and optionally treating pain, is disclosed. The composition and method utilize a nonopioid analgesic and an endothelin antagonist as active agents to treat fever in mammals, including humans. The composition also is useful in the prevention and treatment of stroke and other cardiovascular disorders, like myocardial infarction.
• Diagnostic Use of Endothelin Etb Receptor Agonists and Eta Receptor Antagonists in Tumor Imaging
  申请人：Gulati Anil

  公开号：US20080260634A1

  公开（公告）日：2008-10-23

  Methods of imaging tumors are disclosed. The methods utilize an endothelin ET B receptor agonist or an endothelin ET A receptor antagonist, in combination with an imaging agent, to detect a tumor in mammals, including humans.
• Method and Composition for Potentiating an Opiate Analgesic
  申请人：Gulati Anil

  公开号：US20100113396A1

  公开（公告）日：2010-05-06

  Composition and methods of treating pain and reducing or reversing tolerance to opiate analgesics are disclosed. The composition and method utilize an opiate analgesic and an endothelin antagonist as active agents to treat pain in mammals, including humans.