5,11-dihydro-11-ethyl-5-methyl-2-(3-pyrrolyl)-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one | 169833-43-6

• 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-5-methyl-2-(3-pyrrolyl)-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
• 英文别名: Dipyridodiazepinone deriv. 42；2-ethyl-9-methyl-5-(1H-pyrrol-3-yl)-2,4,9,15-tetrazatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one
• CAS: 169833-43-6
• 化学式: C₁₈H₁₇N₅O
• 分子量: 319.366
• InChiKey: GNMFKYCBSKMWKN-UHFFFAOYSA-N

物化性质

• 沸点：
  619.5±55.0 °C(Predicted)
• 密度：
  1.277±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  65.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  5,11-dihydro-11-ethyl-5-methyl-2-(3-pyrrolyl)-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one 在 三氯氧磷 作用下， 以 1,1-二氯乙烷 、 N,N-二甲基乙酰胺 为溶剂， 生成 2-(2-Acetylpyrrol-3-yl)-5,11-dihydro-11-ethyl-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one 、 2-(2-acetylpyrrol-4-yl)-5,11-dihydro-11-ethyl-5-methyl-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one
  参考文献：
  名称：

  2-heteroaryl-5,11-dihydro-6H-dipyrido\x9b3,2-B:2',3'-E!\x9b1,4!diazepines and

  摘要：

  治疗HIV-1感染的新化合物。这些是具有以下结构的2-杂环-5,11-二氢-6H-二吡啶\x9b3,2-b:2',3'-e!\x9b1,4!二氮杂环化合物，其中Z为氧、硫、.dbd.NCN或.dbd.NOR.sup.10，Ar为以下结构的基团I、II、III、IV或V。

  公开号：

  US05837704A1
• 作为产物：
  描述：

  5-氨基-2-甲氧基吡啶 在 吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 四丁基氟化铵 、 氢溴酸 、 溴 、 sodium acetate 、 sodium hydride 、 溶剂黄146 、 二甲基亚砜 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 氯仿 、 溶剂黄146 、 xylene 为溶剂， 反应 10.24h， 生成 5,11-dihydro-11-ethyl-5-methyl-2-(3-pyrrolyl)-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

• 2-HETEROARYL-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：EP0745083B1

  公开（公告）日：1998-05-20
• US5837704A
  申请人：——

  公开号：US5837704A

  公开（公告）日：1998-11-17