9-甲基咔唑-2-羧酸 | 89374-81-2

• 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
• 中文名称: 9-甲基咔唑-2-羧酸
• 英文名称: 9-methyl-9H-carbazole-2-carboxylic acid
• 英文别名: 9H-Carbazole-2-carboxylic acid, 9-methyl-；9-methylcarbazole-2-carboxylic acid
• CAS: 89374-81-2
• 化学式: C₁₄H₁₁NO₂
• 分子量: 225.247
• InChiKey: WHOPQFBTXKRKGP-UHFFFAOYSA-N

物化性质

• 沸点：
  389.0±24.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  42.2
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  9-甲基咔唑-2-羧酸 在 叠氮磷酸二苯酯 、 三乙胺 、 三氟乙酸 作用下， 以 叔丁醇 、 二氯甲烷 为溶剂， 反应 18.0h， 以39%的产率得到9-methyl-9H-carbazol-2-amine
  参考文献：
  名称：

  Design, synthesis, and evaluation of potent Wnt signaling inhibitors featuring a fused 3-ring system

  摘要：

  The Wnt signaling pathway is a critical developmental pathway which operates through control of cellular functions such as proliferation and differentiation. Aberrant Wnt signaling has been linked to the formation and metastasis of tumors. Porcupine, a member of the membrane -bound O-acyltransferase family of proteins, is an important component of the Wnt pathway. Porcupine catalyzes the palmitoylation of Wnt proteins, a process needed for their secretion and activity. Here we report a novel series of compounds obtained by a scaffold hybridization strategy from a known porcupine inhibitor class. The leading compound 59 demonstrated subnanomolar inhibition of Wnt signaling in a paracrine cellular assay. Compound 59 also showed excellent chemical, plasma and liver microsomal stabilities. Furthermore, compound 59 exhibited good pharmacokinetic profiles with 30% oral bioavailability in rat. Collectively, these results strongly support further optimization of this novel scaffold to develop better Wnt pathway inhibitors. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.11.026
• 作为产物：
  描述：

  1-甲基吲哚-2-甲醛 在 silica gel 氢氧化钾 作用下， 以 乙醇 、 Petroleum ether 、 苯 为溶剂， 反应 21.58h， 生成 9-甲基咔唑-2-羧酸
  参考文献：
  名称：

  Narasimhan, N. S.; Kusurkar, R. S.; Dhavale, D. D., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1983, vol. 22, # 10, p. 1004 - 1010

  摘要：

  DOI：

文献信息

• Carboxylation of Aryl Triflates with CO₂ Merging Palladium and Visible-Light-Photoredox Catalysts
  作者：Samir Kumar Bhunia、Pritha Das、Shantanu Nandi、Ranjan Jana

  DOI：10.1021/acs.orglett.9b01532

  日期：2019.6.21

  visible-light-promoted, highly practical carboxylation of readily accessible aryl triflates at ambient temperature and a balloon pressure of CO2 by the combined use of palladium and photoredox Ir(III) catalysts. Strikingly, the stoichiometric metallic reductant is replaced by a nonmetallic amine reductant providing an environmentally benign carboxylation process. In addition, one-pot synthesis of a carboxylic

  我们在此报告了在环境温度和CO 2的球囊压力下，易于获得的芳基三氟甲磺酸酯在可见光促进下的高度实用的羧化反应钯和光氧化还原Ir（III）催化剂的组合使用。令人惊讶的是，化学计量的金属还原剂被非金属的胺还原剂所替代，从而提供了对环境无害的羧化过程。另外，通过后期羧化反应已经完成了直接从苯酚的一锅法合成羧酸和雌酮的修饰以及药用药物阿达帕林和贝沙罗汀的简明合成。此外，已经在H型密闭容器中证明了平行的脱羧-羧化反应，这对战略领域是一个有趣的概念。光谱和光谱电化学研究表明，电子从Ir（III）/ DIPEA组合中转移，生成了芳基羧酸盐和Pd（0）用于催化转换。
• Ni-Catalyzed Carboxylation of C(sp²)– and C(sp³)–O Bonds with CO₂
  作者：Arkaitz Correa、Thierry León、Ruben Martin

  DOI：10.1021/ja410883p

  日期：2014.1.22

  an excellent chemoselectivity profile using air-, moisture-insensitive and easy-to-handle nickel precatalysts. Our results render our method a powerful alternative, practicality and novelty aside, to commonly used organic halides as counterparts in carboxylation protocols. Furthermore, this study shows, for the first time, that traceless directing groups allow for the reductive coupling of substrates

  近年来，芳基卤化物和苄基卤化物与 CO2 的羧化取得了重大进展，成为使用化学计量量明确的金属物质的方便替代品。然而，这些过程中的大多数都需要使用自燃和空气敏感试剂，目前的方法主要限于有机卤化物。因此，非常希望发现一种温和的、操作简单的替代羧化反应，该羧化反应在广泛的底物范围内使用容易获得的偶联伙伴发生。在此，我们报告了一种新的协议，该协议涉及 CO2 协同活化的开发和惰性 C(sp(2))-O 和 C(sp(3))-O 键的相当具有挑战性的活化，这些键源自简单且廉价的酒精，这是该领域以前未被认识到的机会。这种前所未有的羧化事件的特点是其简单、温和的反应条件、显着的选择性模式以及使用对空气、水分不敏感且易于处理的镍预催化剂的优异化学选择性曲线。我们的结果使我们的方法成为一种强大的替代方案，实用性和新颖性，可以替代常用的有机卤化物作为羧化方案中的对应物。此外，这项研究首次表明，无痕导向基团允许在没有扩展
• ACYLGUANIDINE DERIVATIVE
  申请人：Kinoyama Isao

  公开号：US20100324017A1

  公开（公告）日：2010-12-23

  An object of the present invention is to provide a novel and excellent agent for treating or preventing dementia, schizophrenia and the like, based on the 5-HT 5A receptor modulating action. It was confirmed that a compound characterized by a structure that a tricyclic hetero ring having a pyrrole ring at the center and guanidine are bonded via a carbonyl group has a potent 5-HT 5A receptor modulating action and an excellent pharmacological action based thereon, and thus, it was found that the compound can be an excellent agent for treating or preventing dementia, schizophrenia, bipolar disorder, or attention deficit hyperactivity disorder, particularly for memory-related functional disorders such as cognitive impairments including dementia and schizophrenia, thereby completing the present invention.

  本发明的目的是提供一种基于5-HT5A受体调节作用的新型优良的治疗或预防痴呆症、精神分裂症等药剂。经证实，一种以三环杂环在中心具有吡咯环，并通过羰基结合了胍的结构特征化合物具有强效的5-HT5A受体调节作用和基于此的优良药理作用，因此，发现该化合物可以成为治疗或预防痴呆症、精神分裂症、躁郁症或注意力缺陷多动障碍等的优良药剂，特别是对于认知障碍包括痴呆症和精神分裂症等的记忆相关功能障碍，从而完成了本发明。
• Design, synthesis of novel benzimidazole derivatives as ENL inhibitors suppressing leukemia cells viability via downregulating the expression of MYC
  作者：Siqi Guo、Tongguan Jia、Xiaoming Xu、Feng Yang、Senhao Xiao、Zeng Hou、Hesong Xu、Shuyuan Ma、Xiao Liu、Cheng Luo、Hualiang Jiang、Hua Chen、Shijie Chen

  DOI：10.1016/j.ejmech.2023.115093

  日期：2023.2

  MOLM-13 cell lines with IC50 values of 4.8 μM and 8.3 μM, respectively, exhibiting ∼7 folds and ∼9 folds more potent inhibition of cell growth than SGC-iMLLT. It could also increase the ENL thermal stability while SGC-iMLLT had no obvious effect on leukemia cells. Moreover, compound 28 could downregulate the expression of target gene MYC either alone or in combination with JQ-1 in cells, which was more effective

  含有潜在药物靶标 YEATS 结构域的十一-十九白血病蛋白 (ENL) 已成为赖氨酸乙酰化的阅读器。带有苯并咪唑支架的 SGC-iMLLT 被确定为一种有效的 ENL 抑制剂，但对混合谱系白血病 (MLL) 重排细胞增殖的活性较弱。在本研究中，通过在 SGC-iMLLT 上进行结构优化，设计并合成了一系列化合物。已对所有化合物的 ENL 抑制活性进行了评估。结果表明化合物13 , 23和28是最具潜力的化合物，IC 50值分别为 14.5 ± 3.0 nM、10.7 ± 5.3 nM 和 15.4 ± 2.2 nM，与 SGC-iMLLT 相似。它们可以与ENL蛋白相互作用，增强其体外热稳定性。其中，SGC-iMLLT 中甲基菲啶酮部分取代吲唑的化合物28对 MV4-11 和 MOLM-13 细胞系表现出显着的抑制活性，IC 50值分别为 4.8 μM 和 8.3 μM，表现出 ~7 倍和
• Pd(II)-catalyzed, directing group-aided C-H arylation, alkylation, benzylation and methoxylation of carbazole-3-carboxamides toward C2,C3,C4 functionalized carbazoles
  作者：Ramandeep Kaur、Harcharan Singh、Srinivasarao Arulananda Babu

  DOI：10.1055/a-2056-2363

  日期：——

  We report the Pd(II)-catalyzed, bidentate directing group 8-aminoquinoline or 2-(methylthio)aniline-assisted β-C-H arylation, alkylation, benzylation and methoxylation of carbazole-3-carboxamide, carbazole-2-carboxamide substrates and construction of C2,C3,C4 functionalized carbazole motifs. The Pd(II)-catalyzed β-C-H arylation reaction was attempted using different directing groups such as 8-aminoquinoline, 2-(methylthio)aniline, 4-amino-2,1,3-benzothiadiazole, 4-methoxyquinolin-8-amine and butan-1-amine. Through optimization of reactions, the 8-aminoquinoline and 2-(methylthio)aniline were found to be suitable directing groups and especially, 2-(methylthio)aniline was found to be an efficient directing group in the Pd(II)-catalyzed β-C-H arylation, alkylation, methoxylation of carbazole-3-carboxamide, carbazole-2-carboxamide substrates. An ample number of β-C-H arylated, alkylated, benzylated and methoxylated carbazole-3-carboxamides were synthesized. The structures of representative β-C(2)-H arylated carbazole and β-C(2)-H methoxylated carbazole motifs were unequivocally confirmed by the single-crystal X-ray structure analysis. Given the wide range of applications of carbazoles in chemical, materials sciences and medicinal chemistry and there have been constant efforts for developing new methods and synthesizing functionalized carbazoles. This work contributes to the expansion of the library of the C2,C3,C4 functionalized carbazole motifs through the Pd(II)-catalyzed directing group-aided site-selective β-C-H activation and functionalization of carbazole-3-carboxamides.

  我们报告了钯(II)催化的双臂定向基团 8-氨基喹啉或 2-(甲硫基)苯胺辅助的 β-C-H 芳基化、烷基化、苄基化和甲氧基化咔唑-3-甲酰胺、咔唑-2-甲酰胺底物以及 C2、C3、C4 功能化咔唑基团的构建。尝试使用不同的指导基团，如 8-氨基喹啉、2-（甲硫基）苯胺、4-氨基-2,1,3-苯并噻二唑、4-甲氧基喹啉-8-胺和丁-1-胺，来催化 β-C-H 芳基化反应。通过优化反应，发现 8-氨基喹啉和 2-（甲硫基）苯胺是合适的指导基团，尤其是 2-（甲硫基）苯胺在钯(II)催化的咔唑-3-甲酰胺和咔唑-2-甲酰胺底物的β-C-H 芳基化、烷基化、甲氧基化反应中是一个有效的指导基团。合成了大量 β-C-H 芳基化、烷基化、苄基化和甲氧基化的咔唑-3-甲酰胺。代表性的 β-C(2)-H 芳基化咔唑和 β-C(2)-H 甲氧基化咔唑基团的结构已通过单晶 X 射线结构分析得到明确证实。鉴于咔唑在化学、材料科学和药物化学中的广泛应用，人们一直在努力开发新方法和合成功能化咔唑。这项研究通过 Pd(II)- 催化定向基团辅助的咔唑-3-羧酰胺的位点选择性 β-C-H 活化和功能化，为扩展 C2、C3、C4 功能化咔唑基团库做出了贡献。