1,1-dimethylethyl (+)-(S)-1,2,4,5,6,7-hexahydro-5-methyl-2-oxoimidazo<4,5,1-jk><1,4>benzodiazepine-6-carboxylate | 164728-86-3

• 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: 1,1-dimethylethyl (+)-(S)-1,2,4,5,6,7-hexahydro-5-methyl-2-oxoimidazo<4,5,1-jk><1,4>benzodiazepine-6-carboxylate
• 英文别名: (1,1-dimethylethyl) (S)-1,2,4,5,6,7-hexahydro-5-methyl-2-oxoimidazo[4,5,1-jk][1,4]benzodiazepine-6-carboxylate；tert-butyl (11S)-11-methyl-2-oxo-1,3,10-triazatricyclo[6.4.1.04,13]trideca-4,6,8(13)-triene-10-carboxylate
• CAS: 164728-86-3
• 化学式: C₁₆H₂₁N₃O₃
• 分子量: 303.361
• InChiKey: AKNJDFXYOMZYIP-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 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-oxoimidazo<4,5,1-jk><1,4>benzodiazepine-6-carboxylate 在 N-溴代丁二酰亚胺(NBS) 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 34.0h， 生成 (+)-(S)-1,2,4,5,6,7-hexahydro-5-methyl-2-oxoimidazo<4,5,1-jk><1,4>benzodiazepine-8-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
• 作为产物：
  描述：

  4-二甲氨基吡啶 、 二碳酸二叔丁酯 在 potassium carbonate 作用下， 以 甲醇 、 乙腈 为溶剂， 以6.4 parts (57.5%)的产率得到1,1-dimethylethyl (+)-(S)-1,2,4,5,6,7-hexahydro-5-methyl-2-oxoimidazo<4,5,1-jk><1,4>benzodiazepine-6-carboxylate
  参考文献：
  名称：

  Anti-HIV-1 tetrahydroimidazo[1,4]benzodiazepin-2-(thi) ones

  摘要：

  新型四氢咪唑并[1,4]苯二氮杂环己烷-2-(硫)酮具有抗HIV-1活性，含有这些化合物作为活性成分的组合物，以及通过给予这些化合物治疗患有HIV-1感染的受试者的方法。这些化合物具有在式(I)中显示的基本结构：##STR1##

  公开号：

  US05270464A1

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.
• Anti-HIV-1 tetrahydroimidazo[1,4]benzodiazepin-2-(thi) ones
  申请人：Janssen Pharmaceutica N.V.

  公开号：US05270464A1

  公开（公告）日：1993-12-14

  Novel tetrahydroimidazo[1,4]benzodiazepin-2-(thi)ones possessing anti-HIV-1 activity, compositions containing these compounds as active ingredients, and methods of treating subjects suffering from HIV-1 infection by administering these compounds. The compounds have the basic structure shown in Formula (I): ##STR1##

  新型四氢咪唑并[1,4]苯二氮杂环己烷-2-(硫)酮具有抗HIV-1活性，含有这些化合物作为活性成分的组合物，以及通过给予这些化合物治疗患有HIV-1感染的受试者的方法。这些化合物具有在式(I)中显示的基本结构：##STR1##