11-cyclopropyl-5,11-dihydro-4-formyl-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepin-6-one | 162255-74-5

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 11-cyclopropyl-5,11-dihydro-4-formyl-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepin-6-one
• 英文别名: 11-Cyclopropyl-5,11-dihydro-4-formyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one；11-Cyclopropyl-6,11-dihydro-6-oxo-5H-dipyrido[3,2-b:2',3'-e][1,4]diazepine-4-carboxaldehyde；2-cyclopropyl-10-oxo-2,4,9,15-tetrazatricyclo[9.4.0.03,8]pentadeca-1(11),3,5,7,12,14-hexaene-7-carbaldehyde
• CAS: 162255-74-5
• 化学式: C₁₅H₁₂N₄O₂
• 分子量: 280.286
• InChiKey: IMROVCLQVRIPAB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  75.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  11-cyclopropyl-5,11-dihydro-4-formyl-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepin-6-one 在 palladium on activated charcoal 氢气 、 sodium hydride 作用下， 以 乙醇 为溶剂， 反应 0.25h， 生成 3-(5-Cyclopropyl-11-oxo-10,11-dihydro-5H-4,5,6,10-tetraaza-dibenzo[a,d]cyclohepten-9-yl)-propionic acid ethyl ester
  参考文献：
  名称：

  Novel Non-nucleoside Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase. 5. 4-Substituted and 2,4-Disubstituted Analogs of Nevirapine

  摘要：

  Molecular modeling analysis of the recently published X-ray crystal structure of nevirapine bound to wild type human immunodeficiency virus type 1 reverse transcriptase (WT-PT) indicated the presence of a lipophilic cavity proximal to the 4-position of the inhibitor. A series of 4-substituted derivatives of nevirapine were thus synthesized to assess structure-activity relationships (SARs) and to see if increased binding to this region might translate into greater activity against mutant RTs. The results show that compounds with an appropriately spaced aryl ring appended to the 4-position of the dipyridodiazepinone ring system show good activity against WT-RT. Furthermore certain derivatives appear to inhibit the Y181C mutant RT. Attempts to combine these results with the recent discovery that 2-substituents enhance activity against the Y181C mutant led to a few compounds with moderate activity against both enzymes. The SAR of these two positions, however, could not be combined in a simple fashion.

  DOI：

  10.1021/jm00024a011
• 作为产物：
  描述：

  11-环丙基-5,11-二氢-4-(羟基甲基)-6H-二吡啶并[3,2-b:2',3'-e][1,4]二氮杂卓-6-酮 在 manganese(IV) oxide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 3.0h， 以60%的产率得到11-cyclopropyl-5,11-dihydro-4-formyl-6H-dipyrido<3,2-b:2',3'-e><1,4>diazepin-6-one
  参考文献：
  名称：

  奈韦拉平及其主要代谢产物的合成

  摘要：

  在工艺优化过程中开发了几种合成方法，用于大规模合成奈韦拉平（1），这是一种HIV-1逆转录酶的非核苷抑制剂。推定的主要代谢物11-环丙基-5,11-二氢-4-羟甲基-6 H- [3,2- b：2'，3'- e ] [1,4]二氮杂6-1-6（2）和氧化2成相应的醛3，中有描述。

  DOI：

  10.1002/jhet.5570320144

文献信息

• 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。
• US5366972A
  申请人：——

  公开号：US5366972A

  公开（公告）日：1994-11-22
• US5620974A
  申请人：——

  公开号：US5620974A

  公开（公告）日：1997-04-15
• Novel Non-nucleoside Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase. 5. 4-Substituted and 2,4-Disubstituted Analogs of Nevirapine
  作者：Terence A. Kelly、John R. Proudfoot、Daniel W. McNeil、Usha R. Patel、Eva David、Karl D. Hargrave、Peter M. Grob、Mario Cardozo、Atul Agarwal、Julian Adams

  DOI：10.1021/jm00024a011

  日期：1995.11

  Molecular modeling analysis of the recently published X-ray crystal structure of nevirapine bound to wild type human immunodeficiency virus type 1 reverse transcriptase (WT-PT) indicated the presence of a lipophilic cavity proximal to the 4-position of the inhibitor. A series of 4-substituted derivatives of nevirapine were thus synthesized to assess structure-activity relationships (SARs) and to see if increased binding to this region might translate into greater activity against mutant RTs. The results show that compounds with an appropriately spaced aryl ring appended to the 4-position of the dipyridodiazepinone ring system show good activity against WT-RT. Furthermore certain derivatives appear to inhibit the Y181C mutant RT. Attempts to combine these results with the recent discovery that 2-substituents enhance activity against the Y181C mutant led to a few compounds with moderate activity against both enzymes. The SAR of these two positions, however, could not be combined in a simple fashion.