3-Nitro-2,4,6-trimethyl-benzylchlorid | 30075-64-0

• 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: 3-Nitro-2,4,6-trimethyl-benzylchlorid
• 英文别名: 3-Nitro-2,4,6-trimethylbenzylchlorid；2-(Chloromethyl)-1,3,5-trimethyl-4-nitrobenzene
• CAS: 30075-64-0
• 化学式: C₁₀H₁₂ClNO₂
• 分子量: 213.664
• InChiKey: UVFATBVNKGVKOJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  45.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-Nitro-2,4,6-trimethyl-benzylchlorid 在 sodium hydroxide 、 sodium hydride 、 氯化铵 、 锌 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.75h， 生成 O-(3-amino-2,4,6-trimethylbenzyl)-N,N-dimethylthiocarbamate
  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：

  2,4,6-三甲基氯苄 在 nitronium tetrafluoborate 作用下， 以 二氯甲烷 为溶剂， 反应 8.0h， 生成 3-Nitro-2,4,6-trimethyl-benzylchlorid
  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

• Chloromethylation with Chloromethyl Methyl Ether and 60%-Fuming Sulfuric Acid. A Simple Synthesis of Some Nitropolymethylbenzyl Chlorides and Dihalopolymethylbenzyl Chlorides
  作者：Hitomi Suzuki

  DOI：10.1246/bcsj.43.3299

  日期：1970.10
• US4105681A
  申请人：——

  公开号：US4105681A

  公开（公告）日：1978-08-08
• US4215215A
  申请人：——

  公开号：US4215215A

  公开（公告）日：1980-07-29
• US4224244A
  申请人：——

  公开号：US4224244A

  公开（公告）日：1980-09-23
• US4319048A
  申请人：——

  公开号：US4319048A

  公开（公告）日：1982-03-09