5-(bromomethyl)-1-SEM-indazole | 187274-94-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡唑类
• 英文名称: 5-(bromomethyl)-1-SEM-indazole
• 英文别名: 2-[[5-(bromomethyl)indazol-1-yl]methoxy]ethyl-trimethylsilane
• CAS: 187274-94-8
• 化学式: C₁₄H₂₁BrN₂OSi
• 分子量: 341.323
• InChiKey: YENPUPAZHBJKAC-UHFFFAOYSA-N

物化性质

• 沸点：
  391.9±32.0 °C(Predicted)
• 密度：
  1.25±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.24
• 重原子数：
  19.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  27.05
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  5-(bromomethyl)-1-SEM-indazole 在 盐酸 、 sodium hydride 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (5S,6S,4R,7R)-1,3-Bis((1H-indazol-5-yl)methyl)-4,7-dibenzyl-5,6-dihydroxy-1,3-diazepin-2-one
  参考文献：
  名称：

  Potent cyclic urea HIV protease inhibitors with benzofused heterocycles as P2/P2′ groups

  摘要：

  A series of benzofused heterocycles was examined to replace the metabolically unstable benzyl alcohol P2/P2' groups of DMP 323 (1). Extremely potent inhibitors of HIV protease (Ki < 0.01 nM) and excellent antiviral activity (IC90 = 8 nM) were found. An X-ray crystal structure of benzimidazolone 5a bound to HIV protease showed H-bonds to Asp30 and a bridging water molecule to Gly48. Copyright (C) 1996 The DuPont Merck Pharmaceutical Company. Published by Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00531-8
• 作为产物：
  描述：

  5-甲基-1H-吲唑 在 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 、 过氧化苯甲酰 作用下， 以 四氯化碳 、 N,N-二甲基甲酰胺 为溶剂， 生成 5-(bromomethyl)-1-SEM-indazole
  参考文献：
  名称：

  Potent cyclic urea HIV protease inhibitors with benzofused heterocycles as P2/P2′ groups

  摘要：

  A series of benzofused heterocycles was examined to replace the metabolically unstable benzyl alcohol P2/P2' groups of DMP 323 (1). Extremely potent inhibitors of HIV protease (Ki < 0.01 nM) and excellent antiviral activity (IC90 = 8 nM) were found. An X-ray crystal structure of benzimidazolone 5a bound to HIV protease showed H-bonds to Asp30 and a bridging water molecule to Gly48. Copyright (C) 1996 The DuPont Merck Pharmaceutical Company. Published by Elsevier Science Ltd

  DOI：

  10.1016/s0960-894x(96)00531-8

文献信息

• Tricyclic ureas: A new class of HIV-1 protease inhibitors
  作者：Wei Han、Jeffrey C. Pelletier、C.Nicholas Hodge

  DOI：10.1016/s0960-894x(98)00659-3

  日期：1998.12

  A new class of tricyclic ureas containing a conformationally constrained proline was designed with the aid of molecular modeling. Efficient stereoselective intermolecular pinacol coupling represented the highlight of the synthesis. These rigid cyclic ureas are active towards HIV-1 protease, with 9 being the most potent compound (Ki = 9 nM) despite interacting with only three side chain binding pockets of HIV protease. (C) 1998 The DuPont Pharmaceuticals Company. Published by Elsevier Science Ltd. All rights reserved.
• Stereospecific Synthesis, Structure−Activity Relationship, and Oral Bioavailability of Tetrahydropyrimidin-2-one HIV Protease Inhibitors
  作者：George V. De Lucca、Jing Liang、Indawati De Lucca

  DOI：10.1021/jm9803626

  日期：1999.1.1

  The use of tetrahydropyrimidinones as an alternate scaffold for designing HIVPR inhibitors has advantages, over the previously disclosed hexahydro-1,3-diazepin-2-ones, of being more unsymmetrical (different P1/P1'), less crystalline, more soluble, and more lipophilic (mono-ol vs diol). They show a better translation of K-i to IC90 for the more polar P2 groups that in general give the more potent enzyme inhibitors. Structure-activity relationship (SAR) studies of the tetrahydropyrimidinones showed that the phenylethyl P1' substituent, the hydroxyl group, and the urea carbonyl are all critical for good activity. However, there was significant flexibility in the possible P2/P2' substituents that could be used. Many analogues that contained identical or different P2/P2' substituents, or only one P2 substituent, were found to have excellent enzyme potency and several had excellent antiviral potency. Several of these compounds were examined for oral bioavailability in the rat or the dog at 10 mg/kg. However, the oral bioavailability of the tetrahydropyrimidinones was, in general, less than the corresponding hexahydro-1,3-diazepin-2-ones. Unfortunately, when all factors are considered, including potency, protein binding, solubility, bioavailability, and resistance profile, the tetrahydropyrimidinones did not offer any advantage over the previously disclosed hexahydro-1,3-diazepin-2-ones series.