8-Methyl-7-(3-methyl-but-2-enyl)-1-thioxo-1,2,6,7,8,9-hexahydro-2,7,9a-triaza-benzo[cd]azulene-5-carbonitrile | 164728-60-3

• 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: 8-Methyl-7-(3-methyl-but-2-enyl)-1-thioxo-1,2,6,7,8,9-hexahydro-2,7,9a-triaza-benzo[cd]azulene-5-carbonitrile
• 英文别名: (11S)-11-methyl-10-(3-methylbut-2-enyl)-2-sulfanylidene-1,3,10-triazatricyclo[6.4.1.04,13]trideca-4(13),5,7-triene-7-carbonitrile
• CAS: 164728-60-3
• 化学式: C₁₇H₂₀N₄S
• 分子量: 312.439
• InChiKey: MMACPMQCCGUQQX-LBPRGKRZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  74.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-Methyl-7-(3-methyl-but-2-enyl)-1-thioxo-1,2,6,7,8,9-hexahydro-2,7,9a-triaza-benzo[cd]azulene-5-carbonitrile 在 二异丁基氢化铝 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 生成 (-)-(S)-1,2,4,5,6,7-Hexahydro-5-methyl-6-(3-methyl-2-butenyl)-2-thioxoimidazol[4,51-jk][1,4]benzodiazepine-8-carboxaldehyde
  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：

  (+)-(S)-1,2,4,5,6,7-hexahydro-5-methyl-2-oxoimidazo<4,5,1-jk><1,4>benzodiazepine-8-carbonitrile 在 盐酸 、 lutidine 、 sodium carbonate 、 trifluoromethanesulfonic acid anhydride 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.5h， 生成 8-Methyl-7-(3-methyl-but-2-enyl)-1-thioxo-1,2,6,7,8,9-hexahydro-2,7,9a-triaza-benzo[cd]azulene-5-carbonitrile
  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.