3,6-dichloro-9-(oxiran-2-ylmethyl)-9H-carbazole | 65679-71-2

• 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: 3,6-dichloro-9-(oxiran-2-ylmethyl)-9H-carbazole
• 英文别名: 3,6-dichloro-9-(oxiran-2-ylmethyl)carbazole
• CAS: 65679-71-2
• 化学式: C₁₅H₁₁Cl₂NO
• mdl: MFCD00218276
• 分子量: 292.164
• InChiKey: WQKPSQDZHVQBOF-UHFFFAOYSA-N

物化性质

• 熔点：
  143 °C

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  17.5
• 氢给体数：
  0
• 氢受体数：
  1

安全信息

• 危险品标志：
  Xi
• 海关编码：
  2933990090
• 包装等级：
  III
• 危险类别：
  9
• 危险性防范说明：
  P501,P273,P260,P270,P264,P280,P391,P314,P337+P313,P305+P351+P338,P301+P312+P330
• 危险品运输编号：
  3077
• 危险性描述：
  H302,H319,H372,H410

反应信息

• 作为反应物：
  描述：

  3,6-dichloro-9-(oxiran-2-ylmethyl)-9H-carbazole 在 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 1-(3,6-dichloro-9H-carbazol-9-yl)-3-(phenylsulfonyl)propan-2-ol
  参考文献：
  名称：

  Development of Proneurogenic, Neuroprotective Small Molecules

  摘要：

  Degeneration of the hippocampus is associated with Alzheimer's disease and occurs very early in the progression of the disease. Current options for treating the cognitive symptoms associated with Alzheimer's are inadequate, giving urgency to the search for novel therapeutic strategies. Pharmacologic agents that safely enhance hippocampal neurogenesis may provide new therapeutic approaches. We discovered the first synthetic molecule, named P7C3, which protects newborn neurons from apopotic cell death, and thus promotes neurogenesis in mice and rats in the subgranular zone of the hippocampal dentate gyrus, the site of normal neurogenesis in adult mammals. We describe the results of a medicinal chemistry campaign to optimize the potency, toxicity profile, and stability of P7C3. Systematic variation of nearly every position of the lead compound revealed elements conducive toward increases in activity and regions subject to modification. We have discovered compounds that are orally available, nontoxic, stable in mice, rats, and cell culture, and capable of penetrating the blood brain barrier. The most potent compounds are active at nanomolar concentrations. Finally, we have identified derivatives that may facilitate mode-of-action studies through affinity chromatography or photo-cross-linking.

  DOI：

  10.1021/ja108211m
• 作为产物：
  描述：

  咔唑 在 N-氯代丁二酰亚胺 、 potassium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 3,6-dichloro-9-(oxiran-2-ylmethyl)-9H-carbazole
  参考文献：
  名称：

  Potential Antimicrobial Isopropanol-Conjugated Carbazole Azoles as Dual Targeting Inhibitors of Enterococcus faecalis

  摘要：

  A series of isopropanol-bridged carbazole azoles as potential antimicrobial agents were designed and synthesized from commercial carbazoles. Bioassay revealed that 3,6-dichlorocarbazolyl triazole 3f could effectively inhibit the growth of E. faecalis with minimal inhibitory concentration of 2 mu g/mL. The active molecule 3f showed lower propensity to trigger the development of resistance in bacteria than norfloxacin and exerted rapidly bactericidal ability. Compound 3f also exhibited low cytotoxicity to normal mammalian RAW264.7 cells. Further mechanism exploration indicated that conjugate 3f was membrane active against E. faecalis and could form 3f-DNA complex by intercalating into DNA of resistant E. faecalis, which might be responsible for its antimicrobial action. Molecular docking showed an efficient binding of triazole derivative 3f with DNA gyrase enzyme through noncovalent interactions.

  DOI：

  10.1021/acsmedchemlett.7b00514

文献信息

• Synthesis and biological evaluation of novel 1,2,4-triazine derivatives bearing carbazole moiety as potent α-glucosidase inhibitors
  作者：Guangcheng Wang、Jing Wang、Dianxiong He、Xin Li、Juan Li、Zhiyun Peng

  DOI：10.1016/j.bmcl.2016.04.071

  日期：2016.6

  A new series of 1,2,4-triazine derivatives bearing carbazole moiety 7a-7p were designed, synthesized, and evaluated for their α-glucosidase inhibitory activity. The majority of the screened compounds displayed potent α-glucosidase inhibitory activity, with IC50 values in the range of 4.27±0.07-47.75±0.25μM as compared to the standard drug acarbose. Among the series, compound 7k represented the most

  设计，合成了一系列新的带有咔唑部分7a-7p的1,2,4-三嗪衍生物，并评估了其对α-葡萄糖苷酶的抑制活性。与标准药物阿卡波糖相比，大多数被筛选的化合物显示出有效的α-葡萄糖苷酶抑制活性，IC50值在4.27±0.07-47.75±0.25μM范围内。在该系列中，化合物7k表现出最强的α-葡萄糖苷酶抑制活性，IC50值为4.27±0.07μM。动力学分析表明，化合物7k是一种非竞争性抑制剂，Ki为4.43μM。此外，通过分子对接证实了化合物7k与α-葡糖苷酶的结合相互作用。这项研究表明，这些带有咔唑部分的1,2,4-三嗪衍生物是一类新型的α-葡萄糖苷酶抑制剂。
• Molecular construction of multitarget neuroprotectors 4.* Synthesis and biological activity of conjugates of carbazoles and tetrahydrocarbazoles
  作者：V. B. Sokolov、A. Yu. Aksinenko、T. V. Goreva、T. A. Epishina、L. G. Dubova、E. S. Dubrovskaya、S. G. Klochkov、P. N. Shevtsov、E. F. Shevtsova、S. O. Bachurin

  DOI：10.1007/s11172-016-1582-x

  日期：2016.9

  Unknown conjugates of carbazoles and tetrahydrocarbazoles were obtained by the alkylation of carbazoles and tetrahydrocarbazoles with 3,6-substituted 9-oxiranylmethylcarbazoles. The influence of synthesized 1-(9Н-carbazol-9-yl)-3-(1,2,3,4-tetrahydro-5Н-pyrido[4,3-b]-indol-5-yl)propan-2-ones on functional characteristics of brain mitochondria has been studied. The potential neuroprotective activity

  咔唑和四氢咔唑的未知共轭物是通过咔唑和四氢咔唑与 3,6-取代的 9-环氧乙烷基甲基咔唑的烷基化获得的。合成1-(9Н-咔唑-9-基)-3-(1,2,3,4-四氢-5Н-吡啶并[4,3-b]-吲哚-5-基)丙-2-的影响对脑线粒体功能特性的研究。已使用谷氨酸毒性模型证明了几种代表性缀合物的潜在神经保护活性。
• Elucidation of antimicrobial activity and mechanism of action by N-substituted carbazole derivatives
  作者：Johannes D. Clausen、Lasse Kjellerup、Karen O'Hanlon Cohrt、John Bondo Hansen、William Dalby-Brown、Anne-Marie L. Winther

  DOI：10.1016/j.bmcl.2017.08.067

  日期：2017.10

  to and inhibits the H+-ATPase within minutes, leading to fungal death after 1–3 h of compound exposure in vitro. The tested compounds are not selective for the fungal H+-ATPase, exhibiting an overlap of inhibitory activity with the mammalian protein family of P-type ATPases; the sarco(endo)plasmic reticulum calcium ATPase (Ca2+-ATPase) and the sodium potassium ATPase (Na+,K+-ATPase). The ion transport

  属于咔唑系列的化合物已被鉴定为有效的真菌质膜质子三磷酸腺苷酶 (H + -ATPase) 抑制剂，具有广谱抗真菌活性。咔唑化合物抑制必需真菌 H + -ATP 酶的三磷酸腺苷 (ATP) 水解活性，从而功能性地抑制质子的排出和细胞外酸化，这些过程负责维持高质膜电位。该化合物类在几分钟内结合并抑制 H + -ATP 酶，在体外暴露化合物 1-3 小时后导致真菌死亡。测试的化合物对真菌 H + -ATP 酶没有选择性，表现出与哺乳动物 P 型 ATP 酶蛋白家族重叠的抑制活性；肌（内）质网钙 ATP 酶（Ca 2+ -ATP 酶）和钠钾 ATP 酶（Na + ,K + -ATP 酶）。P 型 ATP 酶中的离子转运通过 ATP 转化为二磷酸腺苷 (ADP) 和磷酸盐来激发，因此咔唑衍生物介导的一般抑制机制可能会阻断活性位点。然而，生化研究表明，增加 ATP 浓度不会改变咔唑的抑制活性，表明它们
• Discovery of Inhibitors of MicroRNA-21 Processing Using Small Molecule Microarrays
  作者：Colleen M. Connelly、Robert E. Boer、Michelle H. Moon、Peter Gareiss、John S. Schneekloth

  DOI：10.1021/acschembio.6b00945

  日期：2017.2.17

  identification of small molecules that bind to and perturb the function of microRNAs is an attractive approach for the treatment for microRNA-associated pathologies. However, there are only a few small molecules known to interact directly with microRNAs. Here, we report the use of a small molecule microarray (SMM) screening approach to identify low molecular weight compounds that directly bind to a pre-miR-21

  识别与microRNA结合并扰乱其功能的小分子是治疗microRNA相关疾病的一种有吸引力的方法。但是，只有很少的小分子可以直接与microRNA相互作用。在这里，我们报告使用小分子微阵列（SMM）筛选方法来鉴定直接结合pre-miR-21发夹的低分子量化合物。使用此方法鉴定的化合物对RNA表现出良好的亲和力（范围为0.8-2.0μM），并且不由聚阳离子支架组成。几种具有最高亲和力的化合物会抑制Dicer介导的加工，而在线探针实验表明，该化合物与Dicer部位近端的发夹顶端环结合。
• Molecular design of multitarget neuroprotectors 2. Synthesis and bioactivity of carbazole—γ-carboline conjugates
  作者：V. B. Sokolov、A. Yu. Aksinenko、T. V. Goreva、T. A. Epishina、V. V. Grigor´ev、A. V. Gabrel´yan、D. V. Vinogradova、L. G. Dubova、P. N. Shevtsov、E. F. Shevtsova、S. O. Bachurin

  DOI：10.1007/s11172-016-1460-6

  日期：2016.5

  Earlier unknown conjugates of carbazoles and γ-carbolines were obtained by the reaction of 3,6-substituted 9-oxiranylmethylcarbazoles and 2,8-substituted 2,3,4,5-tetrahydro-1H-pyrido-[4,3]indoles. The effects of synthesized 1-(9H-carbazol-9-yl)-3-(1,2,3,4-tetrahydro-5H-pyrido-[4,3-b]indol-5-yl)propan-2-ones and their hydrochlorides on neuronal NMDA receptors, polymerization of tubulin to form microtubules, and functional characteristics of rat liver mitochondria were studied.

  以前未知的氮杂环类和γ-咔啉的结合物是通过3,6-取代的9-氧杂基甲基咔唑与2,8-取代的2,3,4,5-四氢-1H-吡啶[4,3]吲哚的反应获得的。研究了合成的1-(9H-咔唑-9-基)-3-(1,2,3,4-四氢-5H-吡啶-[4,3-b]吲哚-5-基)丙-2-酮及其盐酸盐对神经元NMDA受体、微管形成中微管蛋白的聚合以及大鼠肝线粒体功能特性的影响。