1-(4-bromobenzoyl)-9H-β-carboline-3-carboxylic acid

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: 1-(4-bromobenzoyl)-9H-β-carboline-3-carboxylic acid
• 英文别名: 1-(4-bromobenzoyl)-9H-pyrido[3,4-b]indole-3-carboxylic acid
• 化学式: C₁₉H₁₁BrN₂O₃
• 分子量: 395.212
• InChiKey: LBUUONNXSWCYSF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  83
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(4-bromobenzoyl)-9H-β-carboline-3-carboxylic acid 、 4-羟基苄胺 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以59.8 %的产率得到1-(4-bromobenzoyl)-N-(4-hydroxybenzyl)-9H-pyrido[3,4-b]indole-3-carboxamide
  参考文献：
  名称：

  Marinacarboline 类似物作为多西紫杉醇耐药三阴性乳腺癌 STAT3 通路抑制剂的设计、合成和生物活性

  摘要：

  转移性三阴性乳腺癌 (mTNBC) 是一种致命类型的乳腺癌 (BC)，信号转导和转录激活因子 3 (STAT3) 已成为 mTNBC 的有效靶点。在本研究中，化合物MC0704被发现是一种新型合成 STAT3 通路抑制剂，其潜在的抗肿瘤活性在多西紫杉醇耐药的 TNBC 细胞中使用体外和体内模型得到证实。基于 marinacarboline (MC)，合成了一系列 β-咔啉衍生物，并研究了它们对多西紫杉醇耐药 MDA-MB-231 (MDA-MB-231-DTR) 细胞的抗肿瘤活性。结合抗增殖和 STAT3 抑制活性，MC0704被选为最有前途的 β-咔啉化合物。MC0704在体外有效地阻止了 MDA-MB-231-DTR 细胞的转移潜能，并且MC0704和多西他赛的组合在异种移植小鼠模型中表现出有效的抗肿瘤活性。这些发现表明，MC0704可以作为具有多西紫杉醇耐药性的 TNBC 患者的靶向治疗药物的主要候选药物。

  DOI：

  10.1021/acs.jmedchem.2c01115
• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以60.3 %的产率得到1-(4-bromobenzoyl)-9H-β-carboline-3-carboxylic acid
  参考文献：
  名称：

  Marinacarboline 类似物作为多西紫杉醇耐药三阴性乳腺癌 STAT3 通路抑制剂的设计、合成和生物活性

  摘要：

  转移性三阴性乳腺癌 (mTNBC) 是一种致命类型的乳腺癌 (BC)，信号转导和转录激活因子 3 (STAT3) 已成为 mTNBC 的有效靶点。在本研究中，化合物MC0704被发现是一种新型合成 STAT3 通路抑制剂，其潜在的抗肿瘤活性在多西紫杉醇耐药的 TNBC 细胞中使用体外和体内模型得到证实。基于 marinacarboline (MC)，合成了一系列 β-咔啉衍生物，并研究了它们对多西紫杉醇耐药 MDA-MB-231 (MDA-MB-231-DTR) 细胞的抗肿瘤活性。结合抗增殖和 STAT3 抑制活性，MC0704被选为最有前途的 β-咔啉化合物。MC0704在体外有效地阻止了 MDA-MB-231-DTR 细胞的转移潜能，并且MC0704和多西他赛的组合在异种移植小鼠模型中表现出有效的抗肿瘤活性。这些发现表明，MC0704可以作为具有多西紫杉醇耐药性的 TNBC 患者的靶向治疗药物的主要候选药物。

  DOI：

  10.1021/acs.jmedchem.2c01115

文献信息

• A versatile route to the synthesis of 1-substituted β-carbolines by a single step Pictet–Spengler cyclization
  作者：Mei-Lin Yang、Ping-Chung Kuo、Amooru G. Damu、Ren-Jie Chang、Wen-Fei Chiou、Tian-Shung Wu

  DOI：10.1016/j.tet.2006.08.081

  日期：2006.11

  A one-step conversion of L-tryptophan and activated aldehydes (1,2-dicarbonyl compounds) directly to 1-substituted beta-carbolines without formation of the tetrahydro derivatives under modified Pictet-Spengler conditions was described. Moreover, a practical application for the synthesis of a natural 1-substituted beta-carboline, luzongerine A, isolated from Illigera luzonensis was also successfully carried out utilizing this protocol. The effects of synthetic compounds 11 and 11a on nitric oxide (NO) production in LPS/IFN-gamma stimulated RAW 264.7 macrophage cells were evaluated in vitro. They displayed significant dose-dependent inhibition of inducible nitric oxide synthase (iNOS). (c) 2006 Elsevier Ltd. All rights reserved.
• Synthesis, in vitro anti-inflammatory and cytotoxic evaluation, and mechanism of action studies of 1-benzoyl-β-carboline and 1-benzoyl-3-carboxy-β-carboline derivatives
  作者：Mei-Lin Yang、Ping-Chung Kuo、Tsong-Long Hwang、Wen-Fei Chiou、Keduo Qian、Chin-Yu Lai、Kuo-Hsiung Lee、Tian-Shung Wu

  DOI：10.1016/j.bmc.2011.01.034

  日期：2011.3

  In the present study, various 1-substituted and 1,3-disubstituted beta-carboline derivatives were synthesized by a modified single-step Pictet-Spengler reaction. The compounds were examined for cytotoxicity and anti-inflammatory activity, as measured by the inhibition of prostaglandin E-2 (PGE(2)) production and nitric oxide (NO) production. While only two compounds (28 and 31) showed marginal cytotoxicity against four human cancer cell lines, most of the tested compounds exhibited potent inhibitory activity of both NO and PGE(2) production. Moreover, compounds 6 and 16 significantly reduced the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX2), suggesting that beta-carboline analogs can inhibit NO and PGE(2) production at the translational level. In addition, several of the beta-carboline derivatives (1, 2, 48, 11, 13, 22, 25, 27, 31, and 41-43) displayed significant inhibitory activity of superoxide anion (O-2(center dot-)) generation or elastase release compared to the reference compound, with 6 being the most potent. N-Formyl-L-methionyl-phenylalanine (FMLP)-induced phosphorylation of c-Jun N-terminal kinase (JNK) and protein kinase B (AKT) were also inhibited by 6, suggesting that it suppresses human neutrophil functions by inhibiting the activation of JNK and AKT signaling pathways. Therefore, the synthetic 1-benzoyl-3-carboxy beta-carboline analogs may have great potential to be developed as anti-inflammatory agents. (C) 2011 Elsevier Ltd. All rights reserved.
• Design, Synthesis, and Biological Activity of Marinacarboline Analogues as STAT3 Pathway Inhibitors for Docetaxel-Resistant Triple-Negative Breast Cancer
  作者：Woong Sub Byun、Hyewon Lim、Junhwa Hong、Eun Seo Bae、Seok Beom Lee、Younggwan Kim、Jeeyeon Lee、Sang Kook Lee、Suckchang Hong

  DOI：10.1021/acs.jmedchem.2c01115

  日期：2023.2.23

  triple-negative breast cancer (mTNBC) is a fatal type of breast cancer (BC), and signal transducer and activator of transcription 3 (STAT3) has emerged as an effective target for mTNBC. In the present study, compound MC0704 was found to be a novel synthetic STAT3 pathway inhibitor, and its potential antitumor activity was demonstrated using in vitro and in vivo models in docetaxel-resistant TNBC cells. Based

  转移性三阴性乳腺癌 (mTNBC) 是一种致命类型的乳腺癌 (BC)，信号转导和转录激活因子 3 (STAT3) 已成为 mTNBC 的有效靶点。在本研究中，化合物MC0704被发现是一种新型合成 STAT3 通路抑制剂，其潜在的抗肿瘤活性在多西紫杉醇耐药的 TNBC 细胞中使用体外和体内模型得到证实。基于 marinacarboline (MC)，合成了一系列 β-咔啉衍生物，并研究了它们对多西紫杉醇耐药 MDA-MB-231 (MDA-MB-231-DTR) 细胞的抗肿瘤活性。结合抗增殖和 STAT3 抑制活性，MC0704被选为最有前途的 β-咔啉化合物。MC0704在体外有效地阻止了 MDA-MB-231-DTR 细胞的转移潜能，并且MC0704和多西他赛的组合在异种移植小鼠模型中表现出有效的抗肿瘤活性。这些发现表明，MC0704可以作为具有多西紫杉醇耐药性的 TNBC 患者的靶向治疗药物的主要候选药物。