1,1-dimethylethyl (-)-(S)-1,2,4,5,6,7-hexahydro-5-methyl-2-oxo-8-<(trimethylsilyl)ethynyl>imidazo<4,5,1-jk><1,4>benzodiazepine-6-carboxylate | 164728-90-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 英文名称: 1,1-dimethylethyl (-)-(S)-1,2,4,5,6,7-hexahydro-5-methyl-2-oxo-8-<(trimethylsilyl)ethynyl>imidazo<4,5,1-jk><1,4>benzodiazepine-6-carboxylate
• 英文别名: tert-butyl (11S)-11-methyl-2-oxo-7-(2-trimethylsilylethynyl)-1,3,10-triazatricyclo[6.4.1.04,13]trideca-4(13),5,7-triene-10-carboxylate
• CAS: 164728-90-9
• 化学式: C₂₁H₂₉N₃O₃Si
• 分子量: 399.565
• InChiKey: LORJBFGKOVUULI-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  61.9
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl (-)-(S)-1,2,4,5,6,7-hexahydro-5-methyl-2-oxo-8-<(trimethylsilyl)ethynyl>imidazo<4,5,1-jk><1,4>benzodiazepine-6-carboxylate 在 palladium on activated charcoal 碳酸氢铵 、 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 tert-butyl (11S)-7-ethyl-11-methyl-2-oxo-1,3,10-triazatricyclo[6.4.1.04,13]trideca-4(13),5,7-triene-10-carboxylate
  参考文献：
  名称：

  Synthesis and Anti-HIV-1 Activity of 4,5,6,7-Tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one (TlBO) Derivatives. 4

  摘要：

  In previous papers, we have described the discovery of a new series of compounds, 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-ones, TlBO (1 and 1a), with potent anti-HIV-1 activity and the synthesis of analogues to better define the structure-activity relationships (SAR) in terms of changes in substituents at the N-6 position and variations of the five-membered urea ring as well as the seven-membered diazepine ring. This paper describes the synthesis of TlBO analogues with various substituents on the aromatic ring and their SAR in terms of anti-HIV-1 properties. Substituents on the 8-position furnished the most rewarding results and gave a large improvement in potency versus the parent compound. These included halogen, thiomethyl, and methyl. Analogues like 8-cyano, -methoxy, and -acetylene were equipotent, while 8-amino, -acetylamino, -dimethylamino, and -nitro were inactive (Table 1). Substituents at the 9-position tended to have little effect on activity, and 10-substituents decreaseed activity. The 8-chloro compound 6a with IC50 = 0.0043 mu M is currently under clinical development.

  DOI：

  10.1021/jm00005a006
• 作为产物：
  描述：

  1,1-dimethylethyl (+)-(S)-1,2,4,5,6,7-hexahydro-5-methyl-2-oxoimidazo<4,5,1-jk><1,4>benzodiazepine-6-carboxylate 在 copper(l) iodide 、 四(三苯基膦)钯 、 thallium(III) acetate 、 一氯化碘 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 138.0h， 生成 1,1-dimethylethyl (-)-(S)-1,2,4,5,6,7-hexahydro-5-methyl-2-oxo-8-<(trimethylsilyl)ethynyl>imidazo<4,5,1-jk><1,4>benzodiazepine-6-carboxylate
  参考文献：
  名称：

  Synthesis and Anti-HIV-1 Activity of 4,5,6,7-Tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one (TlBO) Derivatives. 4

  摘要：

  In previous papers, we have described the discovery of a new series of compounds, 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-ones, TlBO (1 and 1a), with potent anti-HIV-1 activity and the synthesis of analogues to better define the structure-activity relationships (SAR) in terms of changes in substituents at the N-6 position and variations of the five-membered urea ring as well as the seven-membered diazepine ring. This paper describes the synthesis of TlBO analogues with various substituents on the aromatic ring and their SAR in terms of anti-HIV-1 properties. Substituents on the 8-position furnished the most rewarding results and gave a large improvement in potency versus the parent compound. These included halogen, thiomethyl, and methyl. Analogues like 8-cyano, -methoxy, and -acetylene were equipotent, while 8-amino, -acetylamino, -dimethylamino, and -nitro were inactive (Table 1). Substituents at the 9-position tended to have little effect on activity, and 10-substituents decreaseed activity. The 8-chloro compound 6a with IC50 = 0.0043 mu M is currently under clinical development.

  DOI：

  10.1021/jm00005a006

文献信息

• Synthesis and Anti-HIV-1 Activity of 4,5,6,7-Tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one (TlBO) Derivatives. 4
  作者：Winston Ho、Michael J. Kukla、Henry J. Breslin、Donald W. Ludovici、Philip P. Grous、Craig J. Diamond、Milton Miranda、James D. Rodgers、Chih Y. Ho

  DOI：10.1021/jm00005a006

  日期：1995.3

  In previous papers, we have described the discovery of a new series of compounds, 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-ones, TlBO (1 and 1a), with potent anti-HIV-1 activity and the synthesis of analogues to better define the structure-activity relationships (SAR) in terms of changes in substituents at the N-6 position and variations of the five-membered urea ring as well as the seven-membered diazepine ring. This paper describes the synthesis of TlBO analogues with various substituents on the aromatic ring and their SAR in terms of anti-HIV-1 properties. Substituents on the 8-position furnished the most rewarding results and gave a large improvement in potency versus the parent compound. These included halogen, thiomethyl, and methyl. Analogues like 8-cyano, -methoxy, and -acetylene were equipotent, while 8-amino, -acetylamino, -dimethylamino, and -nitro were inactive (Table 1). Substituents at the 9-position tended to have little effect on activity, and 10-substituents decreaseed activity. The 8-chloro compound 6a with IC50 = 0.0043 mu M is currently under clinical development.