4,5,6,7-四氢-5-甲基咪唑并(4,5,1-jk)(1,4)苯并二氮杂卓-2(1H)-酮 | 126233-79-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯二氮卓类
• 中文名称: 4,5,6,7-四氢-5-甲基咪唑并(4,5,1-jk)(1,4)苯并二氮杂卓-2(1H)-酮
• 中文别名: 4(3H)-嘧啶酮,3-甲基-2-(甲硫基)-6-苯基-
• 英文名称: 4,5,6,7-tetrahydro-5-methylimidazo<4,5,1-jk><1,4>benzodiazepin-2(1H)-one
• 英文别名: 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one；4,5,6,7-tetrahydro-5-methylimidazo(4,5,1-jk)[1,4]benzodiazepin-2(1H)-one；4,5,6,7-Tetrahydro-5-methylimidazo(4,5,1-jk)(1,4)benzodiazepin-2(1H)-one；11-methyl-1,3,10-triazatricyclo[6.4.1.04,13]trideca-4,6,8(13)-trien-2-one
• CAS: 126233-79-2
• 化学式: C₁₁H₁₃N₃O
• 分子量: 203.244
• InChiKey: GTNCOIIPIKEYMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  15
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  44.4
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,5,6,7-四氢-5-甲基咪唑并(4,5,1-jk)(1,4)苯并二氮杂卓-2(1H)-酮 、 1-bromo-2,3-dimethyl-2-butene 在 sodium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 22.5h， 以72%的产率得到6-(2,3-Dimethyl-2-buten-1-yl)-4,5,6,7-tetrahydro-5-methylimidazo-(4,5,1-jk)(1,4)-benzodiazepin-2(1H)-one
  参考文献：
  名称：

  Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one (TIBO) derivatives

  摘要：

  A series of 6-substituted 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-ones (9) have been synthesized and tested for their ability to inhibit the replication of the HIV-1 virus in MT-4 cells. Two synthetic methods are described, one of which allows the synthesis of single enantiomers of the final products. A structure-activity study was done within the series of compounds to determine the optimum group for the 6-position substitution and to determine whether the activity was enantiospecific at the 5-position, which was substituted with a methyl group. The best analogue, 9jj, inhibited HIV-1 with an IC50 of 4-mu-M, which is comparable to the activity level of DDI, a 2',3'-dideoxynucleoside-type structure undergoing clinical trials as an anti-AIDS therapy.

  DOI：

  10.1021/jm00106a040
• 作为产物：
  描述：

  2-溴-3-硝基苯甲酸甲酯 在 palladium on activated charcoal 2-羟基吡啶 、 lithium aluminium tetrahydride 、 硫酸 、 氢气 、 sodium carbonate 作用下， 以 四氢呋喃 、 溶剂黄146 、 xylene 、 正丁醇 为溶剂， 42.0 ℃ 、413.69 kPa 条件下， 反应 51.67h， 生成 4,5,6,7-四氢-5-甲基咪唑并(4,5,1-jk)(1,4)苯并二氮杂卓-2(1H)-酮
  参考文献：
  名称：

  Synthesis and anti-HIV-1 activity of 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-one (TIBO) derivatives

  摘要：

  A series of 6-substituted 4,5,6,7-tetrahydro-5-methylimidazo[4,5,1-jk][1,4]benzodiazepin-2(1H)-ones (9) have been synthesized and tested for their ability to inhibit the replication of the HIV-1 virus in MT-4 cells. Two synthetic methods are described, one of which allows the synthesis of single enantiomers of the final products. A structure-activity study was done within the series of compounds to determine the optimum group for the 6-position substitution and to determine whether the activity was enantiospecific at the 5-position, which was substituted with a methyl group. The best analogue, 9jj, inhibited HIV-1 with an IC50 of 4-mu-M, which is comparable to the activity level of DDI, a 2',3'-dideoxynucleoside-type structure undergoing clinical trials as an anti-AIDS therapy.

  DOI：

  10.1021/jm00106a040

文献信息

• [EN] TRICYCLIC COMPOUNDS TO DEGRADE NEOSUBSTRATES FOR MEDICAL THERAPY<br/>[FR] COMPOSÉS TRICYCLIQUES POUR DÉGRADER DES NÉO-SUBSTRATS POUR UNE THÉRAPIE MÉDICALE
  申请人：C4 THERAPEUTICS INC

  公开号：WO2022081927A1

  公开（公告）日：2022-04-21

  The invention provides tricyclic compounds that degrade neosubstrates for use in the treatment of disorders described herein, including, for example, abnormal cellular proliferation, neurodegenerative diseases, and autoimmune diseases.

  本发明提供了三环化合物，用于治疗本文所述的疾病，包括但不限于异常细胞增殖、神经退行性疾病和自身免疫性疾病，这些化合物可以降解新的底物。
• [EN] TRICYCLIC HETEROBIFUNCTIONAL COMPOUNDS FOR DEGRADATION OF TARGETED PROTEINS<br/>[FR] COMPOSÉS HÉTÉROBIFONCTIONNELS TRICYCLIQUES POUR LA DÉGRADATION DE PROTÉINES CIBLÉES
  申请人：C4 THERAPEUTICS INC

  公开号：WO2022081928A1

  公开（公告）日：2022-04-21

  Heterobifunctional compounds for targeted protein degradation that include a tricyclic cereblon binder linked to an appropriate protein targeting ligand to degrade a targeted disease-mediating protein of interest are provided.

  本发明提供了用于靶向蛋白降解的异双功能化合物，其中包括一个三环Cereblon结合剂，连接到一个适当的蛋白靶向配体，以降解感兴趣的靶向疾病介导蛋白质。
• [EN] SUBSTITUTED BENZIMIDAZOLES AS NON-NUCLEOSIDE INHIBITORS OF REVERSE TRANSCRIPTASE<br/>[FR] BENZIMIDAZOLES SUBSTITUES EN TANT QU'INHIBITEURS NON NUCLEOSIDIQUES DE LA TRANSCRIPTASE INVERSE
  申请人：US HEALTH

  公开号：WO2001014343A1

  公开（公告）日：2001-03-01

  Benzimidazole derivatives substituted in position 2 by a 2,6 difluorophenyl and/or in position 1 by a 2,6-difluorobenzyl group are HIV-1 reverse transcriptase inhibitors useful in treatment of HIV infections.

  2-位置被2,6-二氟苯基和/或1-位置被2,6-二氟苄基取代的苯并咪唑衍生物是HIV-1反转录酶抑制剂，可用于治疗HIV感染。
• Substituted benzimidazoles as non-nucleoside inhibitors of reverse transcriptase
  申请人：——

  公开号：US20030191160A1

  公开（公告）日：2003-10-09

  The present invention provides compositions and methods for the treatment of HIV infection. In particular, the present invention provides non-nucleoside inhibitors of reverse transcriptase (RT), as well as methods to treat HIV infection using these non-nucleoside inhibitors of RT. In preferred embodiments, the present invention provides a novel class of substituted benzimidazoles, effective in the inhibition of human immunodeficiency virus (HIV) RT.

  本发明提供了治疗HIV感染的组合物和方法。特别是，本发明提供了反转录酶（RT）非核苷类抑制剂，以及使用这些非核苷类RT抑制剂治疗HIV感染的方法。在优选实施例中，本发明提供了一类新型的取代苯并咪唑，能够有效抑制人类免疫缺陷病毒（HIV）RT。
• Pfaendler, Hans Rudolf; Weisner, Frank, Heterocycles, 1995, vol. 40, # 2, p. 717 - 728
  作者：Pfaendler, Hans Rudolf、Weisner, Frank

  DOI：——

  日期：——