11-ethyl-8-nitro-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one | 135795-56-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 11-ethyl-8-nitro-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
• 英文别名: 5,11-dihydro-11-ethyl-8-nitro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one；5,11-Dihydro-11-ethyl-8-nitro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-on；2-ethyl-13-nitro-2,4,9,15-tetrazatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one
• CAS: 135795-56-1
• 化学式: C₁₃H₁₁N₅O₃
• 分子量: 285.262
• InChiKey: IONMZUZWLQKNOV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  104
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  11-ethyl-8-nitro-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one 在 盐酸 、 硫酸 、 sodium hydride 、 溶剂黄146 、 sodium iodide 、 tin(ll) chloride 、 sodium nitrite 作用下， 反应 3.33h， 生成 5,11-dihydro-11-ethyl-8-iodo-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
  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
• 作为产物：
  描述：

  2-氯-N-[2-(乙胺基)吡啶-3-基]-5-硝基吡啶-3-甲酰胺 在 ethyl acetate n-hexane 作用下， 以 邻二甲苯 为溶剂， 反应 4.0h， 以to give 0.93 g of the title compound的产率得到11-ethyl-8-nitro-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
  参考文献：
  名称：

  5,11-dihyro-6H-dipyrido[3,2-B:2',3'-e][1,3]diazepines and their use in

  摘要：

  本发明涉及一种新型的5,11-二氢-6H-二吡啶[3,2-b; 2',3'-e][1,4]二氮杂环。该化合物可用于预防或治疗HIV感染。

  公开号：

  US05620974A1

文献信息

• 8-arylalkyl- and
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US05705499A1

  公开（公告）日：1998-01-06

  Disclosed are novel 8-arylalkyl-5,11-dihydro-6H-dipyrido\x9b3,2-b:2',3'-e!\x9b1,4!diazepines. These are useful in the treatment of HIV-1 infection.

  公开的是新型的8-芳基烷基-5,11-二氢-6H-二吡啶[3,2-b:2',3'-e]![1,4]二氮杂环。这些化合物在治疗HIV-1感染中是有用的。
• 5,11-dihydro-6H-dipyrido(3,2-B:2',3'-E)(1,4)diazepines and their use in
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US05366972A1

  公开（公告）日：1994-11-22

  Disclosed are novel 5,11-dihydro-6H-dipyrido[3,2-b; 2',3'-e][1,4]diazepines. These are useful in the prevention or treatment of HIV infection.

  本文披露了新型的5,11-二氢-6H-二吡啶并[3,2-b; 2',3'-e][1,4]二氮杂环。这些化合物在预防或治疗HIV感染方面具有用处。
• 5,11-dihyro-6H-dipyrido[3,2-B:2',3'-e][1,3]diazepines and their use in
  申请人：Boehringer Ingelheim Pharmaceuticals, Inc.

  公开号：US05620974A1

  公开（公告）日：1997-04-15

  Disclosed are novel 5,11-dihydro-6H-dipyrido[3,2-b; 2',3'-e][1,4]diazepines. These are useful in the prevention or treatment of HIV infection.

  本发明涉及一种新型的5,11-二氢-6H-二吡啶[3,2-b; 2',3'-e][1,4]二氮杂环。该化合物可用于预防或治疗HIV感染。
• Exploiting the anti-HIV 6-desfluoroquinolones to design multiple ligands
  作者：Luca Sancineto、Nunzio Iraci、Maria Letizia Barreca、Serena Massari、Giuseppe Manfroni、Gianmarco Corazza、Violetta Cecchetti、Alessandro Marcello、Dirk Daelemans、Christophe Pannecouque、Oriana Tabarrini

  DOI：10.1016/j.bmc.2014.07.018

  日期：2014.9

  It is getting clearer that many drugs effective in different therapeutic areas act on multiple rather than single targets. The application of polypharmacology concepts might have numerous advantages especially for disease such as HIV/AIDS, where the rapid emergence of resistance requires a complex combination of more than one drug. In this paper, we have designed three hybrid molecules combining WM5, a quinolone derivative we previously identified as HIV Tat-mediated transcription (TMT) inhibitor, with the tricyclic core of nevirapine and BILR 355BS (BILR) non-nucleoside reverse transcriptase inhibitors (NNRTIs) to investigate whether it could be possible to obtain molecules acting on both transcription steps of the HIV replicative cycle. One among the three designed multiple ligands, reached this goal. Indeed, compound 1 inhibited both TMT and reverse transcriptase (RT) activity. Unexpectedly, while the anti-TMT activity exerted by compound 1 resulted into a selective inhibition of HIV-1 reactivation from latently infected OM10.1 cells, the anti-RT properties shown by all of the synthesized compounds did not translate into an anti-HIV activity in acutely infected cells. Thus, we have herein produced the proof of concept that the design of dual TMT-RT inhibitors is indeed possible, but optimization efforts are needed to obtain more potent derivatives.
• 8-Arylalkyl- and 8-arylheteroalkyl-5, 11-dihydro-6H-dipyrido-[3,2-b:2', 3'-e][1,4]diazepines and their use in the prevention or treatment of HIV infection
  申请人：BOEHRINGER INGELHEIM PHARMACEUTICALS INC.

  公开号：EP0767172B1

  公开（公告）日：2003-03-26