(4-Bromophen-1-yl)(1-methylethylidene)amine | 40938-44-1

• 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: (4-Bromophen-1-yl)(1-methylethylidene)amine
• 英文别名: p-Brom-N-(1-methylethyliden)benzamin；N-Isopropyliden-4-bromanilin；N-(4-bromophenyl)propan-2-imine
• CAS: 40938-44-1
• 化学式: C₉H₁₀BrN
• 分子量: 212.089
• InChiKey: JOZHBQVUTXCRMF-UHFFFAOYSA-N

物化性质

• 沸点：
  76-80 °C(Press: 3 Torr)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  12.4
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  (4-Bromophen-1-yl)(1-methylethylidene)amine 在 sodium tetrahydroborate 、 氨 、 水 作用下， 以 乙醇 为溶剂， 反应 2.17h， 生成 4-溴-N-异丙基苯胺
  参考文献：
  名称：

  Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold

  摘要：

  Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. We reasoned that an intermediate level of flexibility will provide high selectivity for FXa considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. We studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate 23 was identified, synthesized, and found to inhibit FXa with a K-i of 28 mu M. Optimization of derivative 23 resulted in the design of a potent dicarboxamide 47, which displayed a K-i of 135 nM. Dicarboxamide 47 displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 mu M and 20.2 mu M, respectively, which are comparable to those of clinically relevant agents. Dicarboxamide 47 is expected to serve as an excellent lead for further anticoagulant discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2012.06.032
• 作为产物：
  描述：

  α-(p-bromophenylamino)isobutyronitrile 以52%的产率得到(4-Bromophen-1-yl)(1-methylethylidene)amine
  参考文献：
  名称：

  Prosyanik, A. V.; Kol'tsov, N. Yu.; Romanchenko, V. A., Journal of Organic Chemistry USSR (English Translation), 1986, vol. 22, # 7, p. 1330 - 1337

  摘要：

  DOI：

文献信息

• <i>N</i>-Alkylideneanilines. III. Behavior of<i>N</i>-Isopropylideneanilines in Methanol-d₄
  作者：Hiizu Iwamura、Michiko Tsuchimoto、Shigeo Nishimura

  DOI：10.1246/bcsj.47.193

  日期：1974.1

  formation of acetone dimethyl acetal take place as revealed by NMR spectra of the solutions. The H–D exchange reaction is favored by electron-releasing ring substituents and yet is considerably slower than the rates of the E–Z isomerization of the corresponding imines. The carbinolamine ethers are formed when the substituents are strongly electronegative. Formation of acetone dimethyl acetal occurs additionally

  当 N-异亚丙基苯胺溶解在甲醇-d4 中时，溶液的 NMR 光谱揭示了三种类型的反应，即异亚丙基部分中的质子交换、甲醇胺醚的形成和苯胺的释放以及丙酮二甲基乙缩醛的形成。H-D 交换反应有利于释放电子的环取代基，但比相应亚胺的 E-Z 异构化速率要慢得多。当取代基具有强电负性时，会形成甲醇胺醚。丙酮二甲基乙缩醛的形成另外与带有卤素原子作为环取代基的亚胺一起发生。提出了竞争反应机制。
• Cabelkova-Taguchi, Lubomira M.; Warkentin, John, Canadian Journal of Chemistry, 1981, vol. 59, p. 100 - 105
  作者：Cabelkova-Taguchi, Lubomira M.、Warkentin, John

  DOI：——

  日期：——
• An Efficient Synthesis of Aromatic Acetonyl Imines
  作者：Joel Morris、Donn G. Wishka

  DOI：10.1021/jo00113a057

  日期：1995.4
• PROSYANIK A. V.; KOLTSOV N. YU.; ROMANCHENKO V. A., ZH. ORGAN. XIMII, 22,(1986) N 7, 1474-1482
  作者：PROSYANIK A. V.、 KOLTSOV N. YU.、 ROMANCHENKO V. A.

  DOI：——

  日期：——
• Potent direct inhibitors of factor Xa based on the tetrahydroisoquinoline scaffold
  作者：Rami A. Al-Horani、Akul Y. Mehta、Umesh R. Desai

  DOI：10.1016/j.ejmech.2012.06.032

  日期：2012.8

  Direct inhibition of coagulation factor Xa (FXa) carries significant promise for developing effective and safe anticoagulants. Although a large number of FXa inhibitors have been studied, each can be classified as either possessing a highly flexible or a rigid core scaffold. We reasoned that an intermediate level of flexibility will provide high selectivity for FXa considering that its active site is less constrained in comparison to thrombin and more constrained as compared to trypsin. We studied several core scaffolds including 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid for direct FXa inhibition. Using a genetic algorithm-based docking and scoring approach, a promising candidate 23 was identified, synthesized, and found to inhibit FXa with a K-i of 28 mu M. Optimization of derivative 23 resulted in the design of a potent dicarboxamide 47, which displayed a K-i of 135 nM. Dicarboxamide 47 displayed at least 1852-fold selectivity for FXa inhibition over other coagulation enzymes and doubled PT and aPTT of human plasma at 17.1 mu M and 20.2 mu M, respectively, which are comparable to those of clinically relevant agents. Dicarboxamide 47 is expected to serve as an excellent lead for further anticoagulant discovery. (C) 2012 Elsevier Masson SAS. All rights reserved.