1-chloro-8-methoxy-5H-pyrido<4,3-b>indole | 111380-56-4

• 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: 1-chloro-8-methoxy-5H-pyrido<4,3-b>indole
• 英文别名: 4-chloro-6-methoxy-γ-carboline；1-chloro-8-methoxy-5H-pyrido[4,3-b]indole
• CAS: 111380-56-4
• 化学式: C₁₂H₉ClN₂O
• 分子量: 232.669
• InChiKey: ZAXFXUUEPGQAHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  37.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-chloro-8-methoxy-5H-pyrido<4,3-b>indole 在 N-溴代丁二酰亚胺(NBS) 、 lithium aluminium tetrahydride 、 三溴化硼 作用下， 以 四氢呋喃 为溶剂， 生成 9-Bromo-5H-pyrido[4,3-b]indol-8-ol
  参考文献：
  名称：

  Structure-activity relationship of bromoeudistomin D, a powerful Ca2+ releaser in skeletal muscle sarcoplasmic reticulum

  摘要：

  Bromoeudistomin D and 9-methyl-7-bromoeudistomin D which have a beta-carboline skeleton are powerful Ca2+ releasers from skeletal muscle sarcoplasmic reticulum exhibiting caffeine-like properties. We examined the effects of bromoeudistomin D analogues on Ca(2+)-induced Ca2+ release from skeletal muscle sarcoplasmic reticulum. Among bromoeudistomin D analogues, the Ca(2+)-releasing activities of carboline derivatives were higher than those of carbazole derivatives, suggesting that a carboline skeleton is significantly important for the manifestation of Ca(2+)-releasing activity and Ca2+ sensitivity of Ca(2+)-induced Ca2+ release. On the contrary, the analogues which have a carbazole skeleton and bromine at C-6 inhibit both Ca(2+)- and caffeine-induced Ca2+ release. 9-Methyl-substitution of the analogue elevated its Ca(2+)-releasing activity. Moreover, there is a close correlation between the enhancement of [3H]ryanodine binding to sarcoplasmic reticulum by the analogues and the activation of Ca2+ release by them. Bromoudistomin D analogues may provide valuable information about the structure-function relationship of the ryanodine receptor/Ca2+ release channels in skeletal muscle sarcoplasmic reticulum.

  DOI：

  10.1016/0922-4106(95)90040-3
• 作为产物：
  描述：

  4-肼基-2-吡啶酮 在 palladium on activated charcoal 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 25.75h， 生成 1-chloro-8-methoxy-5H-pyrido<4,3-b>indole
  参考文献：
  名称：

  1-Amino-substituted 4-methyl-5H-pyrido[4,3-b]indoles (.gamma.-carbolines) as tricyclic analogs of ellipticines: a new class of antineoplastic agents

  摘要：

  A series of 1-amino-substituted 4-methyl-5H-pyrido[4,3-b]indoles that are structurally related to ellipticines by deletion of a ring have been synthesized in order to evaluate their DNA affinity, their in vitro cytotoxicity on L1210 cultured cells, and their in vivo antitumor activity. Among 24 derivatives that have been prepared and studied for the structure-activity relationship in this new class of antineoplastic agents, those that have a NH(CH2)3N(R)2 side chain (R = CH3 or C2H5) at their 1-position, a 4-methyl group, and an 8-OH substituent, either with a 5-NH or with a 5-NCH3 group, show the most potent cytotoxicities on L1210 cultured cells and in vivo antitumor properties in P388 and L1210 leukemia systems. In vivo antineoplastic activity of the most potent products was confirmed in P388 and L1210 leukemia systems. In vivo antineoplastic activity of the most potent products was confirmed on other mouse experimental tumors from the standard NCI screening:B16 melanoma and C38 adenocarcinoma.

  DOI：

  10.1021/jm00397a023

文献信息

• Structure-Based Design of γ-Carboline Analogues as Potent and Specific BET Bromodomain Inhibitors
  作者：Xu Ran、Yujun Zhao、Liu Liu、Longchuan Bai、Chao-Yie Yang、Bing Zhou、Jennifer L. Meagher、Krishnapriya Chinnaswamy、Jeanne A. Stuckey、Shaomeng Wang

  DOI：10.1021/acs.jmedchem.5b00613

  日期：2015.6.25

  Small-molecule inhibitors of bromodomain and extra terminal proteins (BET), including BRD2, BRD3, and BRD4 proteins have therapeutic potential for the treatment of human cancers and other diseases and conditions. In this paper, we report the design, synthesis, and evaluation of γ-carboline-containing compounds as a new class of small-molecule BET inhibitors. The most potent inhibitor (compound 18, RX-37)

  溴结构域和额外末端蛋白（BET）的小分子抑制剂，包括BRD2，BRD3和BRD4蛋白，具有治疗人类癌症以及其他疾病和状况的治疗潜力。在本文中，我们报告了作为一种新型小分子BET抑制剂的含γ-咔啉化合物的设计，合成和评估。从这项研究中获得的最有效的抑制剂（化合物18，RX-37）与BET溴结构域蛋白（BRD2，BRD3和BRD4）结合，其K i值为3.2–24.7 nM，与其他非BET含溴结构域的蛋白相比，具有较高的选择性蛋白质。化合物18有力和选择性地抑制人急性白血病细胞系中含有重排的混合谱系白血病1基因的细胞生长。我们确定了以1.4Å分辨率与BRD4 BD2配合使用的18的共晶体结构，这为该化合物的高结合亲和力及其进一步的基于结构的优化提供了坚实的结构基础。化合物18代表用于开发用于治疗人类癌症和其他病症的新型疗法的有前途的先导化合物。
• [EN] BET BROMODOMAIN INHIBITORS AND THERAPEUTIC METHODS USING THE SAME<br/>[FR] INHIBITEURS DE BROMODOMAINES BET ET MÉTHODES THÉRAPEUTIQUES LES UTILISANT
  申请人：UNIV MICHIGAN

  公开号：WO2014164596A1

  公开（公告）日：2014-10-09

  Inhibitors of BET bromodomains and compositions containing the same are disclosed. Methods of using the BET bromodomain inhibitors in the treatment of diseases and conditions wherein inhibition of BET bromodomain provides a benefit, like cancers, also are disclosed.

  本文披露了BET bromodomain抑制剂及含有它们的组合物。还披露了使用BET bromodomain抑制剂治疗疾病和状况的方法，其中BET bromodomain的抑制提供益处，如癌症等疾病。
• BET bromodomain inhibitors and therapeutic methods using the same
  申请人：THE REGENTS OF THE UNIVERSITY OF MICHIGAN

  公开号：US10391175B2

  公开（公告）日：2019-08-27

  Inhibitors of BET bromodomains and compositions containing the same are disclosed. Methods of using the BET bromodomain inhibitors in the treatment of diseases and conditions wherein inhibition of BET bromodomain provides a benefit, like cancers, also are disclosed.

  本研究公开了 BET 溴基链抑制剂和含有这些抑制剂的组合物。此外，还公开了将 BET 溴基链抑制剂用于治疗 BET 溴基链抑制可带来益处的疾病和病症（如癌症）的方法。
• US2014/256706
  申请人：——

  公开号：——

  公开（公告）日：——
• BISAGNI, EMILE;NGUYEN, CHI HUNG;PIERRE, ALAIN;PEPIN, ODILE;COINTET, PAUL +, J. MED. CHEM., 31,(1988) N 2, 398-405
  作者：BISAGNI, EMILE、NGUYEN, CHI HUNG、PIERRE, ALAIN、PEPIN, ODILE、COINTET, PAUL +

  DOI：——

  日期：——