Dimethyl-(2,4,6-trimethyl-3-nitro-phenyl)-amine | 250650-88-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: Dimethyl-(2,4,6-trimethyl-3-nitro-phenyl)-amine
• 英文别名: N,N,2,4,6-pentamethyl-3-nitroaniline
• CAS: 250650-88-5
• 化学式: C₁₁H₁₆N₂O₂
• 分子量: 208.26
• InChiKey: MGQJAEWPQOROIW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  49.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Dimethyl-(2,4,6-trimethyl-3-nitro-phenyl)-amine 在 palladium on activated charcoal ammonium formate 作用下， 以 甲醇 为溶剂， 生成 2,4,6-trimethyl-3-(N,N-dimethylamino)aniline
  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：

  N,N,2,4,6-五甲基苯胺 在 甲基叔丁基醚 、 硝酸 、 硫酸 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 1.0h， 以84%的产率得到Dimethyl-(2,4,6-trimethyl-3-nitro-phenyl)-amine
  参考文献：
  名称：

  通过硝酸盐单硝化芳族化合物

  摘要：

  带有碱性氮原子的芳族化合物可以转化为相应的硝酸盐。化合物的单硝化反应可以通过将盐的二氯甲烷溶液添加到硫酸中，或将乙酰氯（或三氟乙酸酐）添加到盐的二氯甲烷溶液中来进行。除其他优点外，该协议还提供了最方便，最可靠的方式来防止硝化过度/欠燃，尤其适用于规模放大。

  DOI：

  10.1016/j.tetlet.2007.10.027

文献信息

• Mono-nitration of aromatic compounds via nitrate salts
  申请人：Cedilote Miall

  公开号：US20070255057A1

  公开（公告）日：2007-11-01

  A method of nitrating a compound selected from the group consisting of is provided.

  提供了一种从所选化合物中硝化的方法。
• Mono-nitration of aromatic compounds
  申请人：F. Hoffmann-La Roche AG

  公开号：EP2327677A1

  公开（公告）日：2011-06-01

  A process to produce a compound of the formula is provided.

  一种生产式化合物的工艺 的工艺。
• US7429589B2
  申请人：——

  公开号：US7429589B2

  公开（公告）日：2008-09-30
• [EN] MONO-NITRATION OF AROMATIC COMPOUNDS<br/>[FR] MONO-NITRATION DE COMPOSÉS AROMATIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2007125034A2

  公开（公告）日：2007-11-08

  [EN] A method of nitrating a compound selected from the group consisting of Formulas (AA) (BB) (CC) (DD) wherein Ar is a nitratable aromatic ring, R¹, R², R³, and R⁴ are hydrogen, alkyl or an aromatic groups, G is selected from the group consisting of CR¹R², O, S, SO and SO₂, R is a heterocyclic ring or other groups bearing a basic nitrogen atom 10 and n is an an integer of 1 to 12 is provided.
  [FR] L'invention concerne un procédé de nitration d'un composé choisi parmi le groupe comprenant les formules (AA) (BB) (CC) (DD), dans lesquelles Ar est un anneau aromatique pouvant être nitraté, R¹, R², R³, et R⁴ représentent l'hydrogène, un groupe alkyle ou un groupe aromatique, G est choisi parmi le groupe comprenant CR¹R², O, S, SO et SO₂, R est un anneau hétérocyclique ou d'autres groupes portant un atome d'azote basique et n est un nombre entier compris entre 1 et 12.
• 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.