Ethyl 3-(1,3-benzodioxol-5-yl)-2-(3-fluoro-4-methoxybenzoyl)-4-nitrobutanoate | 220584-76-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: Ethyl 3-(1,3-benzodioxol-5-yl)-2-(3-fluoro-4-methoxybenzoyl)-4-nitrobutanoate
• CAS: 220584-76-9
• 化学式: C₂₁H₂₀FNO₈
• 分子量: 433.39
• InChiKey: VJXNAXTTZKWLTK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  117
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  Ethyl 3-(1,3-benzodioxol-5-yl)-2-(3-fluoro-4-methoxybenzoyl)-4-nitrobutanoate 在 Ra-Ni 盐酸 、 sodium hydroxide 、 氢气 、 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 、 二氯甲烷 、 溶剂黄146 、 乙腈 为溶剂， 反应 23.5h， 生成 ethyl (2R,3R,4S)-4-(1,3-benzodioxol-5-yl)-1-[2-[3-chloropropylsulfonyl(propyl)amino]ethyl]-2-(3-fluoro-4-methoxyphenyl)pyrrolidine-3-carboxylate
  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
• 作为产物：
  描述：

  3-氟-4-甲氧基苯甲酸 在 potassium tert-butylate 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 Ethyl 3-(1,3-benzodioxol-5-yl)-2-(3-fluoro-4-methoxybenzoyl)-4-nitrobutanoate
  参考文献：
  名称：

  Pyrrolidine-3-carboxylic Acids as Endothelin Antagonists. 5. Highly Selective, Potent, and Orally Active ET_A Antagonists

  摘要：

  The synthesis and structure-activity relationships (SAR) of a series of pyrrolidine-3-carboxylic acids as endothelin antagonists are described. The data shows an increase in selectivity when the methoxy of Atrasentan (ABT-627) is replaced with methyl, and the benzodioxole is replaced with dihydrobenzofuran. Adding a fluorine further increases the binding activity and provides a metabolically stable and orally bioavailable ETA-selective antagonist.

  DOI：

  10.1021/jm010237l