[3-(2-{5-Chloro-2-ethyl-9-methyl-10-oxo-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3(8),4,6,11,13-hexaen-13-yl}ethyl)phenyl]urea

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: [3-(2-{5-Chloro-2-ethyl-9-methyl-10-oxo-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3(8),4,6,11,13-hexaen-13-yl}ethyl)phenyl]urea
• 英文别名: [3-[2-(5-chloro-2-ethyl-9-methyl-10-oxo-2,4,9,15-tetrazatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-13-yl)ethyl]phenyl]urea
• 化学式: C₂₃H₂₃ClN₆O₂
• 分子量: 450.928
• InChiKey: RMKJJNGAUVCDBG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2,6-二氯-3-硝基吡啶 在 platinum(IV) oxide 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 2,6-二叔丁基-4-甲基苯酚 、 硫酸 、 氢气 、 sodium hydride 、 溶剂黄146 、 三乙胺 、 N,N-二异丙基乙胺 、 sodium iodide 、 tin(ll) chloride 、 sodium nitrite 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-二甲基甲酰胺 、 xylene 为溶剂， 125.0 ℃ 、1.03 MPa 条件下， 反应 63.33h， 生成 [3-(2-{5-Chloro-2-ethyl-9-methyl-10-oxo-2,4,9,15-tetraazatricyclo[9.4.0.0^{3,8}]pentadeca-1(15),3(8),4,6,11,13-hexaen-13-yl}ethyl)phenyl]urea
  参考文献：
  名称：

  Novel Nonnucleoside Inhibitors of HIV-1 Reverse Transcriptase. 7. 8-Arylethyldipyridodiazepinones as Potent Broad-Spectrum Inhibitors of Wild-Type and Mutant Enzymes

  摘要：

  Like other nonnucleoside inhibitors of HIV-1 reverse transcriptase, the dipyridodiazepinone nevirapine (Viramune, 1) selects for drug resistant variants of HIV-1, both in cell culture and in patients. In particular, the mutation of residue 181 from tyrosine to cysteine (Y181C) is associated with resistance to most reported nonnucleoside inhibitors. Introduction of an arylethyl substituent at the 8-position of the tricyclic dipyridodiazepinone skeleton confers enhanced potency against Y181C RT. Several analogues of this series display good broad spectrum potency against a panel of mutant enzymes.

  DOI：

  10.1021/jm9707028

文献信息

• US5705499A
  申请人：——

  公开号：US5705499A

  公开（公告）日：1998-01-06
• Novel Nonnucleoside Inhibitors of HIV-1 Reverse Transcriptase. 7. 8-Arylethyldipyridodiazepinones as Potent Broad-Spectrum Inhibitors of Wild-Type and Mutant Enzymes
  作者：Janice M. Klunder、MaryAnn Hoermann、Charles L. Cywin、Eva David、Janice R. Brickwood、Racheline Schwartz、Kevin J. Barringer、Daniel Pauletti、Cheng-Kon Shih、David A. Erickson、Christopher L. Sorge、David P. Joseph、Susan E. Hattox、Julian Adams、Peter M. Grob

  DOI：10.1021/jm9707028

  日期：1998.7.1

  Like other nonnucleoside inhibitors of HIV-1 reverse transcriptase, the dipyridodiazepinone nevirapine (Viramune, 1) selects for drug resistant variants of HIV-1, both in cell culture and in patients. In particular, the mutation of residue 181 from tyrosine to cysteine (Y181C) is associated with resistance to most reported nonnucleoside inhibitors. Introduction of an arylethyl substituent at the 8-position of the tricyclic dipyridodiazepinone skeleton confers enhanced potency against Y181C RT. Several analogues of this series display good broad spectrum potency against a panel of mutant enzymes.