乙酸-(2,4,6-三甲基-3-硝基-苯基酯) | 115231-65-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚酯
• 中文名称: 乙酸-(2,4,6-三甲基-3-硝基-苯基酯)
• 英文名称: 3-Nitro-2,4,6-trimethylphenylacetat
• 英文别名: acetic acid-(2,4,6-trimethyl-3-nitro-phenyl ester)；Essigsaeure-(2,4,6-trimethyl-3-nitro-phenylester)；(2,4,6-Trimethyl-3-nitrophenyl) acetate
• CAS: 115231-65-7
• 化学式: C₁₁H₁₃NO₄
• 分子量: 223.229
• InChiKey: RSWKGTZWXOVVET-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  72.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  乙酸-(2,4,6-三甲基-3-硝基-苯基酯) 在 双(三甲基硅烷基)氨基钾 、 铁粉 、 溶剂黄146 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 3.75h， 生成 ethyl N-[(3-{[N'-(4-chloro-3-methyl-5-isoxazolyl)-N'-(methoxymethyl)amino]sulfonyl}-2-thienyl)carbonyl]-N-(3-acetoxy-2,4,6-trimethylphenyl)carbamate
  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：

  2,4,6-三甲酚 在 硫酸 、 硝酸 、 溶剂黄146 、 三乙胺 作用下， 反应 1.0h， 生成 乙酸-(2,4,6-三甲基-3-硝基-苯基酯)
  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

• Preparation of Quinol Imide Acetates. VI. Scope and Limitations
  作者：Roger Adams、Leslie M. Werbel

  DOI：10.1021/ja01554a052

  日期：1958.11
• FISCHER A.; SEYAN S. S., CAN. J. CHEM., 1978, 56, NO 10, 1348-1357
  作者：FISCHER A.、 SEYAN S. S.

  DOI：——

  日期：——
• Endothelin Antagonists:  Substituted Mesitylcarboxamides with High Potency and Selectivity for ET_A Receptors
  作者：Chengde Wu、E. Radford Decker、Natalie Blok、Huong Bui、Qi Chen、B. Raju、Andree R. Bourgoyne、Vippra Knowles、Ronald J. Biediger、Robert V. Market、Shuqun Lin、Brian Dupré、Timothy P. Kogan、George W. Holland、Tommy A. Brock、Richard A. F. Dixon

  DOI：10.1021/jm9900063

  日期：1999.11.1

  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.