5,11-dihydro-11-ethyl-2-methoxy-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one | 134698-47-8

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 5,11-dihydro-11-ethyl-2-methoxy-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
• 英文别名: Dipyridodiazepinone deriv. 36；2-ethyl-5-methoxy-9-methyl-2,4,9,15-tetrazatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one
• CAS: 134698-47-8
• 化学式: C₁₅H₁₆N₄O₂
• 分子量: 284.318
• InChiKey: BERPEAVNCCSEPP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  58.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5,11-dihydro-11-ethyl-2-methoxy-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one 在 bis-triphenylphosphine-palladium(II) chloride 、 氢溴酸 、 溶剂黄146 、 N,N-二异丙基乙胺 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.08h， 生成 5,11-dihydro-11-ethyl-5-methyl-2-(4-pyrazolyl)-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
  参考文献：
  名称：

  Novel Non-nucleoside Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase. 4. 2-Substituted Dipyridodiazepinones as Potent Inhibitors of Both Wild-Type and Cysteine-181 HIV-1 Reverse Transcriptase Enzymes

  摘要：

  The major cause of viral resistance to the potent human immunodeficiency virus type 1 reverse transcriptase (RT) inhibitor nevirapine is the mutation substituting cysteine for tyrosine-181 in RT (Y181C RT), An evaluation, against Y181C RT, of previously described analogs of nevirapine revealed that the 2-chlorodipyridodiazepinone 16 is an effective inhibitor of this mutant enzyme. The detailed examination of the structure-activity relationship of 2-substituted dipyridodiazepinones presented below shows that combined activity against the wildtype and Y181C enzymes is achieved with aryl substituents at the 2-position of the tricyclic ring system. In addition, the substitution pattern at C-4, N-5, and N-11 of the dipyridodiazepinone ring system optimum for inhibition of both wild-type and Y181C RT is no longer the 4-methyl-11-cyclopropyl substitution preferred against the wild-type enzyme but rather the 5-methyl-11-ethyl (or 11-cyclopropyl) pattern. The more potent 8-substituted dipyridodiazepinones were evaluated against mutant RT enzymes (L100I RT, K103N RT, P236L RT, and E138K RT) that confer resistance to other non-nucleoside RT inhibitors, and compounds 42, 62, and 67, with pyrrolyl, aminophenyl, and aminopyridyl substituents, respectively, at the 2-position, were found to be effective inhibitors of these mutant enzymes also.

  DOI：

  10.1021/jm00024a010
• 作为产物：
  描述：

  5-氨基-2-甲氧基吡啶 在 吡啶 、 溴 、 sodium acetate 、 sodium hydride 、 二甲基亚砜 作用下， 以 二氯甲烷 、 溶剂黄146 、 xylene 为溶剂， 反应 7.16h， 生成 5,11-dihydro-11-ethyl-2-methoxy-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
  参考文献：
  名称：

  Novel Non-nucleoside Inhibitors of Human Immunodeficiency Virus Type 1 (HIV-1) Reverse Transcriptase. 4. 2-Substituted Dipyridodiazepinones as Potent Inhibitors of Both Wild-Type and Cysteine-181 HIV-1 Reverse Transcriptase Enzymes

  摘要：

  The major cause of viral resistance to the potent human immunodeficiency virus type 1 reverse transcriptase (RT) inhibitor nevirapine is the mutation substituting cysteine for tyrosine-181 in RT (Y181C RT), An evaluation, against Y181C RT, of previously described analogs of nevirapine revealed that the 2-chlorodipyridodiazepinone 16 is an effective inhibitor of this mutant enzyme. The detailed examination of the structure-activity relationship of 2-substituted dipyridodiazepinones presented below shows that combined activity against the wildtype and Y181C enzymes is achieved with aryl substituents at the 2-position of the tricyclic ring system. In addition, the substitution pattern at C-4, N-5, and N-11 of the dipyridodiazepinone ring system optimum for inhibition of both wild-type and Y181C RT is no longer the 4-methyl-11-cyclopropyl substitution preferred against the wild-type enzyme but rather the 5-methyl-11-ethyl (or 11-cyclopropyl) pattern. The more potent 8-substituted dipyridodiazepinones were evaluated against mutant RT enzymes (L100I RT, K103N RT, P236L RT, and E138K RT) that confer resistance to other non-nucleoside RT inhibitors, and compounds 42, 62, and 67, with pyrrolyl, aminophenyl, and aminopyridyl substituents, respectively, at the 2-position, were found to be effective inhibitors of these mutant enzymes also.

  DOI：

  10.1021/jm00024a010

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。
• 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：EP0429987B1

  公开（公告）日：1999-03-17
• 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