12-cyclohexyl-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylic acid methyl ester | 863578-84-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 12-cyclohexyl-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylic acid methyl ester
• 英文别名: methyl 12-cyclohexyl-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylate；methyl 13-cyclohexyl-6,7-dihydroindolo[1,2-d][1,4]benzoxazepine-10-carboxylate
• CAS: 863578-84-1
• 化学式: C₂₄H₂₅NO₃
• 分子量: 375.467
• InChiKey: CCEJTDIOVNWADG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  40.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  12-cyclohexyl-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylic acid methyl ester 在 水 、 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.17h， 生成
  参考文献：
  名称：

  Syntheses and initial evaluation of a series of indolo-fused heterocyclic inhibitors of the polymerase enzyme (NS5B) of the hepatitis C virus

  摘要：

  Herein, we present initial SAR studies on a series of bridged 2-arylindole-based NS5B inhibitors. The introduction of bridging elements between the indole N1 and the ortho-position of the 2-aryl moiety resulted in conformationally constrained heterocycles that possess multiple additional vectors for further exploration. The binding mode and pharmacokinetic (PK) properties of select examples, including: 13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[2,1-d][1,4]benzodiazepine-10-carboxylic acid (7) (IC50 = 0.07 mu M, % F = 18), are reported. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.067
• 作为产物：
  描述：

  2-(4,4,5,5-四甲基-1,3,2-二杂氧戊硼烷-2-基)苯酚 在 四(三苯基膦)钯 、 sodium hydride 、 sodium carbonate 、 lithium chloride 作用下， 以 四氢呋喃 、 乙醇 、 甲苯 为溶剂， 生成 12-cyclohexyl-6,7-dihydro-5-oxa-7a-azadibenzo[a,e]azulene-9-carboxylic acid methyl ester
  参考文献：
  名称：

  Syntheses and initial evaluation of a series of indolo-fused heterocyclic inhibitors of the polymerase enzyme (NS5B) of the hepatitis C virus

  摘要：

  Herein, we present initial SAR studies on a series of bridged 2-arylindole-based NS5B inhibitors. The introduction of bridging elements between the indole N1 and the ortho-position of the 2-aryl moiety resulted in conformationally constrained heterocycles that possess multiple additional vectors for further exploration. The binding mode and pharmacokinetic (PK) properties of select examples, including: 13-cyclohexyl-6-oxo-6,7-dihydro-5H-indolo[2,1-d][1,4]benzodiazepine-10-carboxylic acid (7) (IC50 = 0.07 mu M, % F = 18), are reported. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.067

文献信息

• Inhibitors of HCV replication
  申请人：Hudyma W. Thomas

  公开号：US20060046983A1

  公开（公告）日：2006-03-02

  Indole compounds of Formula I are described. The compounds have activity against hepatitis C virus (HCV) and are useful in treating those infected with HCV. Different forms and compositions comprising the compounds are also described as well as methods of preparing the compounds.

  化合物I的吲哚类化合物已被描述。这些化合物对丙型肝炎病毒（HCV）具有活性，并可用于治疗感染HCV的人。还描述了包含这些化合物的不同形式和组成，以及制备这些化合物的方法。
• Discovery of Conformationally Constrained Tetracyclic Compounds as Potent Hepatitis C Virus NS5B RNA Polymerase Inhibitors
  作者：Kazutaka Ikegashira、Takahiro Oka、Shintaro Hirashima、Satoru Noji、Hiroshi Yamanaka、Yoshinori Hara、Tsuyoshi Adachi、Jun-Ichiro Tsuruha、Satoki Doi、Yasunori Hase、Toru Noguchi、Izuru Ando、Naoki Ogura、Satoru Ikeda、Hiromasa Hashimoto

  DOI：10.1021/jm0610245

  日期：2006.11.30

  We report a new series of hepatitis C virus NS5B RNA polymerase inhibitors containing a conformationally constrained tetracyclic scaffold. SAR studies led to the identification of 6,7-dihydro-5H-benzo[5,6][1,4]diazepino[7,1-a]indoles (19 and 20) bearing a basic pendent group with high biochemical and cellular potencies. These compounds displayed a very small shift in cellular potency when the replicon

  我们报告了一系列新的丙型肝炎病毒 NS5B RNA 聚合酶抑制剂，其中包含构象受限的四环支架。SAR 研究导致鉴定 6,7-二氢-5H-苯并[5,6][1,4]二氮杂[7,1-a]吲哚（19 和 20）具有高生化和细胞效力。当在人血清白蛋白存在下进行复制子测定时，这些化合物在细胞效力方面表现出非常小的变化。
• Tetracyclic fused heterocyclic compound and use thereof as HCV polymerase inhibitor
  申请人：Oka Takahiro

  公开号：US20070049593A1

  公开（公告）日：2007-03-01

  The present invention relates to a tetracyclic fused heterocyclic compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and a therapeutic agent for hepatitis C containing this compound. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.

  本发明涉及一种四环融合杂环化合物，其化学式为[I]，其中每个符号的定义如规范中所述，或其药学上可接受的盐，以及一种丙型肝炎病毒（HCV）聚合酶抑制剂和治疗丙型肝炎的药物，本发明的化合物表现出基于HCV聚合酶抑制活性的抗HCV活性，因此可用作预防或治疗丙型肝炎的药物。
• TETRACYCLIC FUSED HETEROCYCLIC COMPOUND AND USE THEREOF AS HCV POLYMERASE INHIBITOR
  申请人：Oka Takahiro

  公开号：US20120070409A1

  公开（公告）日：2012-03-22

  The present invention relates to a tetracyclic fused heterocyclic compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and a therapeutic agent for hepatitis C containing this compound. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.

  本发明涉及一种四环融合杂环化合物，其表示为以下公式[I]，其中每个符号如规范中所定义，或其药学上可接受的盐，以及一种丙型肝炎病毒（HCV）聚合酶抑制剂和治疗丙型肝炎的药物，本发明的化合物基于HCV聚合酶抑制活性显示出抗HCV活性，可用作预防或治疗丙型肝炎的药物。
• Fused heterotetracyclic compounds and use thereof as hcv polymerase inhibitor
  申请人：Japan Tobacco, Inc.

  公开号：EP2206715A1

  公开（公告）日：2010-07-14

  The present invention relates to a tetracyclic fused heterocyclic compound represented by the following formula [I] wherein each symbol is as defined in the specification, or a pharmaceutically acceptable a salt thereof, and a hepatitis C virus (HCV) polymerase inhibitor and a therapeutic agent for hepatitis C containing this compound. The compound of the present invention shows an anti-HCV activity based on the HCV polymerase inhibitory activity, and useful as an agent for the prophylaxis or treatment of hepatitis C.

  本发明涉及由下式[I]表示的四环融合杂环化合物 其中各符号如说明书中所定义，或其药学上可接受的盐，以及含有该化合物的丙型肝炎病毒（HCV）聚合酶抑制剂和丙型肝炎治疗剂。本发明的化合物具有基于 HCV 聚合酶抑制活性的抗 HCV 活性，可用作丙型肝炎的预防或治疗剂。