9-(trifluoromethoxy)pyrido[2',3':4,5]pyrimido[1,2-α]indole-5,11-dione | 169039-13-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 英文名称: 9-(trifluoromethoxy)pyrido[2',3':4,5]pyrimido[1,2-α]indole-5,11-dione
• 英文别名: 9-(Trifluoromethoxy)pyrido[2',3':4,5]pyrimido[1,2-c]indole-5,11-dione；14-(trifluoromethoxy)-2,4,10-triazatetracyclo[8.7.0.03,8.011,16]heptadeca-1,3(8),4,6,11(16),12,14-heptaene-9,17-dione
• CAS: 169039-13-8
• 化学式: C₁₅H₆F₃N₃O₃
• 分子量: 333.226
• InChiKey: HEADOOAJSIRGQD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  24
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  71.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  9-(trifluoromethoxy)pyrido[2',3':4,5]pyrimido[1,2-α]indole-5,11-dione 在 lithium aluminium tetrahydride 作用下， 以 乙醚 为溶剂， 生成
  参考文献：
  名称：

  Design, Synthesis, and Structure–Activity Relationship Studies of Tryptanthrins As Antitubercular Agents

  摘要：

  The natural product tryptanthrin (la) represents a potential lead for new tuberculosis (TB) drugs since tryptanthrin and its synthetic analogues possess potent in vitro activity against Mycobacterium tuberculosis (Mtb). However, in spite of their in vitro activity, none of these agents have been shown to be efficacious in vivo against animal models of TB. Described herein are syntheses of new tryptanthrin analogues together with a systematic investigation of their in vitro antitubercular activity and ADME properties followed by pharmacokinetic characterization in rodents for the most promising compounds. Those with the best potency and oral bioavailability were progressed to evaluations of efficacy against acute murine TB. The work aimed to prove the concept that this compound class can limit growth of Mtb during infection as well as to establish the SAR for in vitro activity against Mtb and the range of in vitro ADME parameters for this class of natural products. Novel C-11-deoxy (5b) and A-ring-saturated (6) tryptanthrin analogues were discovered that maintained activity against Mtb and showed improved solubility compared to tryptanthrin as well as evidence of oral bioavailability in rodents. However, neither 5b nor 6 demonstrated efficacy against acute murine TB following administration at doses up to 400 mg/kg daily for 4 weeks. Although 5b and 6 failed to inhibit replication or kill Mtb in vivo, they illuminate a path to new structural variations of the tryptanthrin scaffold that may maximize the potential of this class of compounds against TB.

  DOI：

  10.1021/np3007167
• 作为产物：
  描述：

  2-氨基烟酸 、 5-三氟甲氧基吲哚-2,3-二酮 在 氯化亚砜 、 三乙胺 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 反应 5.0h， 以34%的产率得到9-(trifluoromethoxy)pyrido[2',3':4,5]pyrimido[1,2-α]indole-5,11-dione
  参考文献：
  名称：

  氮杂色胺酮类衍生物的合成及在防治植物病原菌细菌、真菌杀菌剂及抗植物病毒制剂的应用

  摘要：

  本发明公开了系列取代的氮杂色胺酮类衍生物，所发明的化合物作为防治植物病原菌细菌、真菌杀菌剂及抗植物病毒制剂的用途，所述衍生物的通式如(I)所示，其中，各取代基的定义详见说明书。该通式所示的化合物对植物病原菌细菌如水稻白叶枯病、真菌如稻瘟病具有较高的杀菌活性和抗植物病毒活性，可用于制备农用特效杀菌剂和抗烟草花叶病毒制剂；

  公开号：

  CN114805353A

文献信息

• Use of tryptanthrin compounds for immune potentiation
  申请人：Chiron Corporation

  公开号：US20040241192A1

  公开（公告）日：2004-12-02

  The invention provides immunostimulatory compositions and methods of administration thereof. Also provided are methods of administering a tryptanthrin compound in an effective amount to enhance the immune response of a subject to an antigen. Also provided are methods of administering an effective amount of a tryptanthrin to stimulate the immune response in a subject for the treatment of cancer. Further provided are methods of administering a tryptanthrin compounds as an immunotherapeutic in the treatment of infectious diseases.

  该发明提供了免疫刺激性组合物及其给药方法。还提供了一种给予色胺酸酸衍生物有效量的方法，以增强受体对抗原的免疫反应。还提供了一种给予有效量色胺酸酸衍生物的方法，以刺激受体的免疫反应，用于治疗癌症。此外，还提供了一种给予色胺酸酸衍生物作为免疫治疗剂治疗传染病的方法。
• USE OF TRYPTANTHRIN COMPOUNDS FOR IMMUNE POTENTIATION
  申请人：VALIANTE Nicholas M.

  公开号：US20120244182A1

  公开（公告）日：2012-09-27

  The invention provides immunostimulatory compositions and methods of administration thereof. Also provided are methods of administering a tryptanthrin compound in an effective amount to enhance the immune response of a subject to an antigen. Also provided are methods of administering an effective amount of a tryptanthrin to stimulate the immune response in a subject for the treatment of cancer. Further provided are methods of administering a tryptanthrin compounds as an immunotherapeutic in the treatment of infectious diseases.

  本发明提供了免疫刺激组合物及其给药方法。还提供了一种给予吲哚丹宁化合物有效量的方法，以增强受体对抗原的免疫反应。还提供了一种给予有效量的吲哚丹宁化合物的方法，以刺激受体对癌症的免疫反应。此外，还提供了将吲哚丹宁化合物作为免疫治疗剂治疗传染病的方法。
• NITROGEN HETEROCYCLIC TRYPTAMINE KETONE DERIVATIVE AND APPLICATION AS IDO1 AND/OR TDO INHIBITOR
  申请人：Peking University

  公开号：EP3421472A1

  公开（公告）日：2019-01-02

  This invention discloses the use of aza-tryptanthrin derivatives as an IDO1 and/or TDO inhibitors, and the derivatives are represented by the general Formula (I). The compounds represented by the Formula (I) have inhibitory effects on indoleamine-2,3-dioxygenase 1 (IDO1) and/or tryptophan-2,3-dioxygenase (TDO), and can be used for treating diseases having the pathological features of IDO1 and/or TDO-mediated tryptophan metabolism, including but not limited to tumors, autoimmune disease, infectious diseases, Alzheimer's disease, depression, anxiety.

  本发明公开了氮杂色蒽衍生物作为IDO1和/或TDO抑制剂的用途，其衍生物由通式（I）表示。由式（I）表示的化合物对吲哚胺-2,3-二氧合酶1（IDO1）和/或色氨酸-2,3-二氧合酶（TDO）具有抑制作用，可用于治疗具有IDO1和/或TDO介导的色氨酸代谢病理特征的疾病，包括但不限于肿瘤、自身免疫性疾病、传染性疾病、阿尔茨海默病、抑郁症、焦虑症等。
• Use of aza-tryptanthrin derivatives as inhibitors of IDO1 and/or TDO
  申请人：Peking University

  公开号：US10669273B2

  公开（公告）日：2020-06-02

  This invention discloses the use of aza-tryptanthrin derivatives as an IDO1 and/or TDO inhibitors, and the derivatives are represented by the general Formula (I). The compounds represented by the Formula (I) have inhibitory effects on indoleamine-2,3-dioxygenase 1 (IDO1) and/or tryptophan-2,3-dioxygenase (TDO), and can be used for treating diseases having the pathological features of IDO1 and/or TDO-mediated tryptophan metabolism, including but not limited to tumors, autoimmune disease, infectious diseases, Alzheimer's disease, depression, anxiety.

  本发明公开了氮杂色蒽衍生物作为IDO1和/或TDO抑制剂的用途，其衍生物由通式（I）表示。由式（I）表示的化合物对吲哚胺-2,3-二氧合酶1（IDO1）和/或色氨酸-2,3-二氧合酶（TDO）具有抑制作用，可用于治疗具有IDO1和/或TDO介导的色氨酸代谢病理特征的疾病，包括但不限于肿瘤、自身免疫性疾病、传染性疾病、阿尔茨海默病、抑郁症、焦虑症等。
• [EN] NITROGEN HETEROCYCLIC TRYPTAMINE KETONE DERIVATIVE AND APPLICATION AS IDO1 AND/OR TDO INHIBITOR<br/>[FR] DÉRIVÉ HÉTÉROCYCLIQUE AZOTÉ TRYPTAMINE CÉTONE ET SON APPLICATION COMME INHIBITEUR D'IDO1 ET/OU TDO<br/>[ZH] 氮杂色胺酮衍生物作为IDO1和/或TDO抑制剂的用途
  申请人：UNIV BEIJING

  公开号：WO2017173973A1

  公开（公告）日：2017-10-12

  本文公开了氮杂色胺酮衍生物作为IDO1和/或TDO抑制剂的用途，所述的衍生物如通式(I)所示。该通式(I)所示的化合物对吲哚胺-2,3-双加氧酶1(IDO1)和/或色氨酸-2,3-双加氧酶(TDO)具有抑制作用，可用于治疗具有IDO1和/或TDO介导的色氨酸代谢的病理学特征的疾病，包括但不限于肿瘤、自身免疫性疾病、感染性疾病、阿尔茨海默病、抑郁症、焦虑症。