(+)-(S)-4,5,6,7-Tetrahydro-8-fluoro-5-methyl-6-(3-methyl-2-butenyl)imidazo<4,5,1-jk><1,4>benzodiazepine-2(1H)-thione | 137332-55-9

• 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: (+)-(S)-4,5,6,7-Tetrahydro-8-fluoro-5-methyl-6-(3-methyl-2-butenyl)imidazo<4,5,1-jk><1,4>benzodiazepine-2(1H)-thione
• 英文别名: (+)-(S)-8-fluoro-4,5,6,7-tetrahydro-5-methyl-6-(3-methyl-2-butenyl)imidazo-[4,5,1-jk] [1,4]benzodiazepin-2(1H)-thione；(+)-(S)-4,5,6,7-Tetrahydro-8-fluoro-5-methyl-6-(3-methyl-2-butenyl)imidazo(4,5,1-jk)[1,4]benzodiazepine-2(1H)-thione；(+)-(S)-4,5,6,7-Tetrahydro-8-fluoro-5-methyl-6-(3-methyl-2-butenyl)imidazo(4,5,1-jk)(1,4)benzodiazepine-2-(1H)-thione；(11S)-7-fluoro-11-methyl-10-(3-methylbut-2-enyl)-1,3,10-triazatricyclo[6.4.1.04,13]trideca-4(13),5,7-triene-2-thione
• CAS: 137332-55-9
• 化学式: C₁₆H₂₀FN₃S
• 分子量: 305.419
• InChiKey: BWXJQEVUMJWLQI-NSHDSACASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  50.6
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  (+)-(S)-6-Fluoro-3-methyl-9-nitro-2,3,4,5-tetrahydro-1H-<1,4>benzodiazepine 在 镍 sodium carbonate 、 一水合肼 、 potassium iodide 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.0h， 生成 (+)-(S)-4,5,6,7-Tetrahydro-8-fluoro-5-methyl-6-(3-methyl-2-butenyl)imidazo<4,5,1-jk><1,4>benzodiazepine-2(1H)-thione
  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

• Regioselectivity in intramolecular nucleophilic aromatic substitution. Synthesis of the potent anti HIV-I 8-halo TIBO analogs
  作者：Kathlyn A. Parker、Craig A. Coburn

  DOI：10.1021/jo00027a019

  日期：1992.1

  Regioselective intramolecular nucleophilic substitution of 2,6-dihalo-3-nitrobenzyl diamines 2b and 2c gave benzodiazepines 3. These intermediates are useful in the preparation of the 8-halo TIBO derivatives 1, inhibitors of HIV-I replication in cell culture.
• US5463049A
  申请人：——

  公开号：US5463049A

  公开（公告）日：1995-10-31
• US5543570A
  申请人：——

  公开号：US5543570A

  公开（公告）日：1996-08-06
• US5599982A
  申请人：——

  公开号：US5599982A

  公开（公告）日：1997-02-04
• 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.