11-ethyl-5-methyl-8-(2-propenyl)-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one | 380378-91-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 11-ethyl-5-methyl-8-(2-propenyl)-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-5-methyl-8-(2-propenyl)-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one；5,11-dihydro-11-ethyl-5-methyl-8-(2-propenyl)-6H-dipyrido[3,2-b:2'.3'-e][1.4]diazepin-6-one；2-ethyl-9-methyl-13-prop-2-enyl-2,4,9,15-tetrazatricyclo[9.4.0.03,8]pentadeca-1(11),3(8),4,6,12,14-hexaen-10-one
• CAS: 380378-91-6
• 化学式: C₁₇H₁₈N₄O
• 分子量: 294.356
• InChiKey: HIQAUQBHQITJKB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  49.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  11-ethyl-5-methyl-8-(2-propenyl)-5,11-dihydro-6H-dipyrido[3,2-b:2',3'-e][1,4]diazepin-6-one 在 臭氧 、 sodium tetrahydroborate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 1.25h， 以72%的产率得到11-乙基-8-(2-羟基乙基)-5-甲基-5,11-二氢-6H-二吡啶并[3,2-B:2',3'-E][1,4]二氮杂卓-6-酮
  参考文献：
  名称：

  Novel 8-Substituted Dipyridodiazepinone Inhibitors with a Broad-Spectrum of Activity against HIV-1 Strains Resistant to Non-nucleoside Reverse Transcriptase Inhibitors

  摘要：

  A series of novel 8-substituted dipyridodiazepinone-based inhibitors were investigated for their antiviral activity against wild type human immunodeficiency virus (HIV-1) and the clinically prevalent K103N/Y181C mutant virus. Our efforts have resulted in a series of benzoic acid analogues that are potent inhibitors of HIV-1 replication against a panel of HIV-1 strains resistant to non-nucleoside reverse transcriptase inhibitors (NNRTIS). Furthermore, the combination of good antiviral potency, a broad spectrum of activity, and an excellent pharmacokinetic profile provides strong justification for the further development of compound 7 as a potential treatment for wild type and NNRTI-resistant HIV-1 infection.

  DOI：

  10.1021/jm050255t
• 作为产物：
  描述：

  2-氯-3-硝基吡啶 在 盐酸 、 bis-triphenylphosphine-palladium(II) chloride 、 2,6-二叔丁基-4-甲基苯酚 、 硫酸 、 sodium hydride 、 溶剂黄146 、 N,N-二异丙基乙胺 、 sodium iodide 、 tin(ll) chloride 、 sodium nitrite 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 xylene 为溶剂， 反应 17.33h， 生成 11-ethyl-5-methyl-8-(2-propenyl)-5,11-dihydro-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

文献信息

• Non-nucleoside reverse transcriptase inhibitors
  申请人：Boehringer Ingelheim (Canada) Ltd.

  公开号：US20040106791A1

  公开（公告）日：2004-06-03

  Compounds represented by formula I: 1 wherein R 1 is H, halogen, (C 1-4 )alkyl, O(C 1-4 )alkyl, and haloalkyl; R 2 is H or (C 1-4 )alkyl; R 3 is H or (C 1-4 )alkyl; R 4 is (C 1-4 )alkyl, (C 1-4 )alkyl(C 3-7 )cycloalkyl, or (C 3-7 )cycloalkyl; and Q is a fused phenyl-5 or 6-membered saturated heterocycle having one to two heteroatoms selected from O and N, said Q being optionally substituted with hydroxy, or (C 1-4 )alkyl which in turn maybe optionally substituted with pyridinyl-N-oxide or C(O)OR wherein R is H or (C 1-4 )alkyl; or a salt thereof. The compounds have inhibitory activity against Wild Type, and single and double mutants strains, of HIV.

  化合物的化学式表示为I： 其中R1为H、卤素、(C1-4)烷基、O(C1-4)烷基和卤代烷基；R2为H或(C1-4)烷基；R3为H或(C1-4)烷基；R4为(C1-4)烷基、(C1-4)烷基(C3-7)环烷基或(C3-7)环烷基；Q为融合的带有一个到两个来自O和N的杂原子的饱和的含有5个或6个成员的苯基杂环，所述Q可以选择地用羟基或(C1-4)烷基取代，而(C1-4)烷基可以选择地用吡啶-N-氧化物或C(O)OR取代，其中R为H或(C1-4)烷基；或其盐。这些化合物对HIV的野生型、单突变体和双突变体菌株具有抑制活性。
• [EN] DIPYRIDODIAZEPINONES AS REVERSE TRANSCRIPTASE INHIBITORS<br/>[FR] DIPYRIDODIAZEPINONES EN TANT QU'INHIBITEURS DE LA TRANSCRIPTASE INVERSE
  申请人：BOEHRINGER INGELHEIM INT

  公开号：WO2003080612A1

  公开（公告）日：2003-10-02

  Disclosed are compounds of formula I:whereinR2 is H, halogen, (C1-4)alkyl, O(C1-4)alkyl, NH(C1-4alkyl) or N(C1-4alkyl)2;R4 is H or CH3;R5 is H or CH3;R12 is H, halogen, (C1-4)alkyl, CF3, or NO2; R13 is H, (C1-4)alkyl, halogen, OH, or NH2, with the proviso that R12 and R13 are not both H; andR14 is COOR14a wherein R14a is H or (C1-6)alkyl; or R14 is (C2-4)alkenyl-COOR14a wherein R14a is as defined herein; or R14 is (C1-4)alkyl-COOR14a wherein R14a is as defined above;or a salt or a prodrug thereof, useful as inhibitors of HIV reverse transcriptase.

  本发明涉及式I的化合物：其中R2为H、卤素、(C1-4)烷基、O(C1-4)烷基、NH(C1-4)烷基或N(C1-4)2；R4为H或CH3；R5为H或CH3；R12为H、卤素、(C1-4)烷基、CF3或NO2；R13为H、(C1-4)烷基、卤素、OH或NH2，但R12和R13不能同时为H；R14为COOR14a，其中R14a为H或(C1-6)烷基；或R14为(C2-4)烯基-COOR14a，其中R14a如上所定义；或R14为(C1-4)烷基-COOR14a，其中R14a如上所定义；或其盐或前药，作为HIV逆转录酶抑制剂。
• NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS
  申请人：BOEHRINGER INGELHEIM (CANADA) LTD.

  公开号：EP1294720B1

  公开（公告）日：2006-04-05
• DIPYRIDODIAZEPINONES AS REVERSE TRANSCRIPTASE INHIBITORS
  申请人：Boehringer Ingelheim International GmbH

  公开号：EP1495024B1

  公开（公告）日：2009-01-28
• US6420359B1
  申请人：——

  公开号：US6420359B1

  公开（公告）日：2002-07-16