2,4,6-三甲基-3-吡咯烷-1-基苯胺 | 250651-02-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 中文名称: 2,4,6-三甲基-3-吡咯烷-1-基苯胺
• 英文名称: 2,4,6-Trimethyl-3-pyrrolidin-1-yl-phenylamine
• 英文别名: 2,4,6-Trimethyl-3-(pyrrolidin-1-yl)aniline；2,4,6-trimethyl-3-pyrrolidin-1-ylaniline
• CAS: 250651-02-6
• 化学式: C₁₃H₂₀N₂
• 分子量: 204.315
• InChiKey: WZOOMOPBWZWSJN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  29.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2,4,6-三甲基-3-吡咯烷-1-基苯胺 在 盐酸 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 17.0h， 生成 N-(4-chloro-3-methyl-5-isoxazolyl)-2-(3-pyrrolidinyl-2,4, 6-trimethylphenylaminocarbonyl)thiophene-3-sulfonamide
  参考文献：
  名称：

  Endothelin Antagonists:  Substituted Mesitylcarboxamides with High Potency and Selectivity for ET_A Receptors

  摘要：

  We have previously disclosed the discovery of 2,4-disubstituted anilinothiophenesulfonamides with potent ETA-selective endothelin receptor antagonism and the subsequent identification of sitaxsentan (TBC11251, 1) as a clinical development compound (Wu et al. J. Med. Chem. 1997, 40, 1682 and 1690). The orally active 1 has demonstrated efficacy in a phase II clinical trial of congestive heart failure (Givertz ct al. Circulation 1998, 98, Abstr. #3044) and was active in rat models of myocardial infarction (Podesser et al. Circulation. 1998, 98, Abstr. #2896) and acute hypoxia-induced pulmonary hypertension (Chen et al. FASEB J. 1996, 10 (3), A104). We now report that an additional substituent at the 6-position of the anilino ring further increases the potency of this series of compounds. It was also found that a wide range of functionalities at the 3-position of the 2,4,6-trisubstituted ring increased ETA selectivity by similar to 10-fold while maintaining in vitro potency, therefore rendering the compounds amenable to fine-tuning of pharmacological and toxicological profiles with enhanced selectivity. The optimal compound in this series was found to be TBC2576 (7u), which has similar to 10-fold higher ETA binding affinity than 1, high ETA/ETB selectivity, and a serum half-life of 7.3 h in rats, as well as in vivo activity.

  DOI：

  10.1021/jm9900063
• 作为产物：
  描述：

  2,4,6-三甲基苯胺 在 palladium on activated charcoal 硫酸 、 硝酸 、 ammonium formate 、 双(三甲基硅烷基)氨基钾 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 为溶剂， 反应 1.5h， 生成 2,4,6-三甲基-3-吡咯烷-1-基苯胺
  参考文献：
  名称：

  Endothelin Antagonists:  Substituted Mesitylcarboxamides with High Potency and Selectivity for ET_A Receptors

  摘要：

  We have previously disclosed the discovery of 2,4-disubstituted anilinothiophenesulfonamides with potent ETA-selective endothelin receptor antagonism and the subsequent identification of sitaxsentan (TBC11251, 1) as a clinical development compound (Wu et al. J. Med. Chem. 1997, 40, 1682 and 1690). The orally active 1 has demonstrated efficacy in a phase II clinical trial of congestive heart failure (Givertz ct al. Circulation 1998, 98, Abstr. #3044) and was active in rat models of myocardial infarction (Podesser et al. Circulation. 1998, 98, Abstr. #2896) and acute hypoxia-induced pulmonary hypertension (Chen et al. FASEB J. 1996, 10 (3), A104). We now report that an additional substituent at the 6-position of the anilino ring further increases the potency of this series of compounds. It was also found that a wide range of functionalities at the 3-position of the 2,4,6-trisubstituted ring increased ETA selectivity by similar to 10-fold while maintaining in vitro potency, therefore rendering the compounds amenable to fine-tuning of pharmacological and toxicological profiles with enhanced selectivity. The optimal compound in this series was found to be TBC2576 (7u), which has similar to 10-fold higher ETA binding affinity than 1, high ETA/ETB selectivity, and a serum half-life of 7.3 h in rats, as well as in vivo activity.

  DOI：

  10.1021/jm9900063

文献信息

• Phenylenediamine urotensin-II receptor antagonists and CCR-9 antagonists
  申请人：Wu Chengde

  公开号：US20050049286A1

  公开（公告）日：2005-03-03

  The present invention relates to urotensin II receptor antagonists, CCR-9 antagonists, pharmaceutical compositions containing them and their use.

  这项发明涉及尿泉素II受体拮抗剂、CCR-9拮抗剂、含有它们的药物组合物以及它们的用途。
• Phenylenediamine Urotensin-II receptor antagonists and CCR-9 antagonists
  申请人：Encysive Pharmaceuticals, Inc.

  公开号：US07319111B2

  公开（公告）日：2008-01-15

  The present invention relates to urotensin II receptor antagonists, CCR-9 antagonists, pharmaceutical compositions containing them and their use.

  本发明涉及尿泊肽 II 受体拮抗剂、CCR-9 拮抗剂、包含它们的制药组合物及其用途。
• CCR-9 antagonists
  申请人：ENCYSIVE PHARMACEUTICALS, INC.

  公开号：EP2415760A2

  公开（公告）日：2012-02-08

  The present invention relates to CCR-9 antagonists, pharmaceutical compositions containing them and their use.

  本发明涉及 CCR-9 拮抗剂、含有 CCR-9 拮抗剂的药物组合物及其用途。
• EP1610753A2
  申请人：——

  公开号：EP1610753A2

  公开（公告）日：2006-01-04
• EP1610753A4
  申请人：——

  公开号：EP1610753A4

  公开（公告）日：2007-07-04