[1-(4-chlorophenyl)-9H-β-carbolin-3-yl]methanol

• 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-chlorophenyl)-9H-β-carbolin-3-yl]methanol
• 英文别名: [1-(4-chlorophenyl)-9H-pyrido[3,4-b]indol-3-yl]methanol
• 化学式: C₁₈H₁₃ClN₂O
• 分子量: 308.767
• InChiKey: UDRXVRIDWUFWQX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  48.9
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  [1-(4-chlorophenyl)-9H-β-carbolin-3-yl]methanol 在 sodium azide 、 copper(ll) sulfate pentahydrate 、 sodium ascorbate 、 三乙胺 作用下， 以 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 叔丁醇 为溶剂， 反应 21.0h， 生成 3-[[4-[(4-bromophenoxy)methyl]triazol-1-yl]methyl]-1-(4-chlorophenyl)-9H-pyrido[3,4-b]indole
  参考文献：
  名称：

  Design and synthesis of C3-tethered 1,2,3-triazolo-β-carboline derivatives: Anticancer activity, DNA-binding ability, viscosity and molecular modeling studies

  摘要：

  A series of new DNA-interactive C3-tethered 1,2,3-triazolo-beta-carboline derivatives have been synthesized via 'click' reaction and evaluated for their in vitro cytotoxicity as well as DNA binding affinity. Interestingly, these hybrids have displayed potent in vitro cytotoxicity in comparison to Harmine against the HT-29 (colon cancer) and HGC-27 (gastric cancer) cell lines. The compounds 7f, 7k, 7n and 7s appear to be more effective against the HGC-27 cell line, among which compound 7f showed the highest cytotoxicity (5.44 +/- 0.58, IC50 mu M). The compounds 7e and 7f appear to be more active against the HT-29 cell line, among which compound 7f exhibited the highest cytotoxicity (3.67 +/- 0.62, IC50 mu M). To gain more insight into the DNA-binding ability, spectroscopic techniques such as UV-Visible, fluorescence and circular dichroism studies were performed. Viscosity measurements and molecular docking studies substantiate that these compounds indeed bind to DNA via the minor groove. (C) 2015 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2015.11.005
• 作为产物：
  描述：

  L-色氨酸 在 potassium permanganate 、 lithium aluminium tetrahydride 、 potassium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.83h， 生成 [1-(4-chlorophenyl)-9H-β-carbolin-3-yl]methanol
  参考文献：
  名称：

  In（OTf）3辅助合成β-咔啉C-3束缚的咪唑并[1,2- a ]嗪衍生物†

  摘要：

  基于β-咔啉的天然产物和合成衍生物的合成由于其药用特性而成为研究的前沿领域之一。设想3-甲酰基-9 H -β-咔啉是潜在的前体，并为在β-咔啉骨架的C-3位置上构建各种杂环结构提供了新的前景。在这种情况下，已经开发出一种有效的方案，用于合成β-咔啉C-3束缚的咪唑并[1,2- a ]吡啶，咪唑并[1,2- a ]嘧啶和咪唑并[1,2- a ]。吡嗪衍生物通过对Groebke–Blackburn–Bienayme（GBB）反应的探索。本协议提供了几个优点，如操作简便，原子经济性高，结构多样性可观以及纯化步骤容易。

  DOI：

  10.1039/c6nj03210a

文献信息

• Synthesis and <i>in vitro</i> cytotoxicity evaluation of β-carboline-linked 2,4-thiazolidinedione hybrids: potential DNA intercalation and apoptosis-inducing studies
  作者：Ramya Tokala、Sowjanya Thatikonda、Sravani Sana、Phanindranath Regur、Chandraiah Godugu、Nagula Shankaraiah

  DOI：10.1039/c8nj03248c

  日期：——

  19e was found to exhibit promising cytotoxic effects against triple negative breast cancer cell line (MDA-MB-231) with IC50 value of 0.97 ± 0.13 μM. Hence, further mechanistic studies of the apoptosis-inducing effect of 19e were conducted on the MDA-MB-23 cell line. Moreover, characteristic apoptotic features such as membrane blebbing, chromatin condensation, and apoptotic body formation were observed

  一系列新的β咔啉噻唑烷二酮的杂交合成并评估在体外针对选定的人癌症细胞系，细胞毒性潜力即，PC-3，A549，MG-63，HCT-15，MDA-MB-231，A431，和PANC-1以及正常的人类细胞系（L-132）。在这个新系列中，发现化合物19e对三阴性乳腺癌细胞系（MDA-MB-231）表现出有希望的细胞毒性作用，IC 50值为0.97±0.13μM。因此，对MDA-MB-23细胞系进行了19e的凋亡诱导作用的进一步机理研究。此外，在19e的作用下，观察到了特征性的凋亡特征，如膜起泡，染色质凝结和凋亡小体形成。使用AO / EB和DAPI染色对MDA-MB-231细胞进行染色。Annexin V-Alexa面粉488 / PI分析证实了明显的早期凋亡诱导作用。值得注意的是，DCFDA分析表明19e诱导了ROS的产生。此外，通过19e的JC-1染色观察到线粒体膜电位塌陷。此外，细胞周期分
• Convenient synthesis of 1-aryl-9H-β-carboline-3-carbaldehydes and their transformation into dihydropyrimidinone derivatives by Biginelli reaction
  作者：Péter Ábrányi-Balogh、András Dancsó、Dávid Frigyes、Balázs Volk、György Keglevich、Mátyás Milen

  DOI：10.1016/j.tet.2014.06.073

  日期：2014.9

  In the present work, a practical synthesis of 1-aryl-β-carboline-3-carbaldehydes as versatile building blocks and their application in Biginelli reaction is reported. The starting material of the four-step synthesis is racemic tryptophan methyl ester. The procedure involves a Pictet–Spengler cyclization, a dehydrogenation, an ester reduction, and an alcohol oxidation step. The β-carboline-3-carbaldehydes

  在目前的工作中，报道了一种实用的1-芳基-β-咔啉-3-甲醛的合成方法，作为通用的结构单元及其在Biginelli反应中的应用。四步合成的起始原料是外消旋色氨酸甲酯。该过程涉及Pictet-Spengler环化，脱氢，酯还原和醇氧化步骤。使用Biginelli反应，将β-咔啉-3-甲醛进一步转化为在位置3上具有药理学意义的二氢嘧啶环的衍生物。
• In(OTf)₃ assisted synthesis of β-carboline C-3 tethered imidazo[1,2-a]azine derivatives
  作者：Nisha Devi、Dharmender Singh、Gurpreet Kaur、Satbir Mor、V. P. R. Kishore Putta、Saibabu Polina、Chandi C. Malakar、Virender Singh

  DOI：10.1039/c6nj03210a

  日期：——

  been developed for the synthesis of β-carboline C-3 tethered imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine, and imidazo[1,2-a]pyrazine derivatives via exploration of the Groebke–Blackburn–Bienayme (GBB) reaction. The present protocol offers several advantages like operational simplicity, high atom economy, appreciable structural diversity and easy purification procedure.

  基于β-咔啉的天然产物和合成衍生物的合成由于其药用特性而成为研究的前沿领域之一。设想3-甲酰基-9 H -β-咔啉是潜在的前体，并为在β-咔啉骨架的C-3位置上构建各种杂环结构提供了新的前景。在这种情况下，已经开发出一种有效的方案，用于合成β-咔啉C-3束缚的咪唑并[1,2- a ]吡啶，咪唑并[1,2- a ]嘧啶和咪唑并[1,2- a ]。吡嗪衍生物通过对Groebke–Blackburn–Bienayme（GBB）反应的探索。本协议提供了几个优点，如操作简便，原子经济性高，结构多样性可观以及纯化步骤容易。
• Design and Synthesis of DNA-Interactive β-Carboline-Oxindole Hybrids as Cytotoxic and Apoptosis-Inducing Agents
  作者：Ramya Tokala、Sowjanya Thatikonda、Usha Sree Vanteddu、Sravani Sana、Chandraiah Godugu、Nagula Shankaraiah

  DOI：10.1002/cmdc.201800402

  日期：2018.9.19

  A new series of (E)‐3‐[(1‐aryl‐9H‐pyrido[3,4‐b]indol‐3‐yl)methylene]indolin‐2‐one hybrids were synthesized and evaluated for their in vitro cytotoxic activity against a panel of selected human cancer cell lines, namely, HCT‐15, HCT‐116, A549, NCI‐H460, and MCF‐7, including HFL. Among the tested compounds, (E)‐1‐benzyl‐5‐bromo‐3‐[1‐(2,5‐dimethoxyphenyl)‐9H‐pyrido[3,4‐b]indol‐3‐yl]methylene}indolin‐2‐one

  合成了一系列新的（E）-3-[（1-芳基-9 H-吡啶基[3,4- b ]吲哚-3-基）亚甲基]吲哚-2-酮杂种并对其体外细胞毒性进行了评估对一组选定的人类癌细胞系，即HCT-15，HCT-116，A549，NCI-H460和MCF-7（包括HFL）具有抗癌活性。在测试的化合物中，（E）-1-苄基-5-溴-3-3-[[1-（2,5-二甲氧基苯基）-9 H-吡啶基[3,4- b ]吲哚-3-基]亚甲基}二氢吲哚-2-酮（10秒）显示针对HCT-15的癌细胞的细胞毒性，其IC 50为1.43±0.26μ值米和GI 50 0.89±0.06μ值米。值得注意的是，使用不同的染色技术（如characterized啶橙/溴化乙锭（AO / EB）和DAPI）对HCT-15细胞系上10 s的凋亡诱导进行了表征。此外，为了了解抗癌作用的机制，进行了多种测定，例如膜联蛋白V-FITC / PI，DCFDA和
• Potent 1,3-disubstituted-9H-pyrido[3,4-b]indoles as new lead compounds in antifilarial chemotherapy1CDRI Communication No. 5795.1
  作者：Sanjay K. Srivastava、Alka Agarwal、Prem M.S. Chauhan、Shiv K. Agarwal、Amiya P. Bhaduri、Som N. Singh、Nigar Fatima、Ranjit K. Chatterjee

  DOI：10.1016/s0968-0896(99)00050-4

  日期：1999.6

  Substituted 9H-pyrido[3,4-b]indoles (beta-carbolines) identified in our laboratory as potential pharmacophore for designing macrofilaricidal agents, have been explored further for identifying the pharmacophore responsible for high order of adulticidal activity. This has led to syntheses and macrofilaricidal evaluations of a number of 1-aryl-9H-pyrido[3,4-b]indole-3-carboxyl derivatives (3-7). The macrofilarical activity was initially evaluated in vivo against Acanthoeilonema viteae. Amongst all the synthesized compounds, only twelve compounds namely 3a, 3c, 3d, 3f, 4c, 4d, 4f, 5a, 6f, 6h, 6i and 7h have exhibited either > 90% micro- or macrofilaricidal activity or sterilization of female worms. These compounds have also been screened against Litomosoides carinii and of these only 3f and 5a have also been found to be active. Finally these two compounds have been evaluated against Brugia malayi. The structure activity relationship (SAR) associated with position-1 and 3 substituents in beta-carbolines have been discussed. It has been observed that the presence of carbomethoxy at position-3 and an aryl substituent at position-1 in beta-carbolines effectively enhance antifilarial activity particularly against A. viteae. Amongst the various compounds screened, methyl 1-(4-methylphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate (4c) has shown highest adulticidal activity and methyl 1-(4-chlorophenyl)1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate (3a) has shown highest microfilaricidal action against A. viteae at 50mg/ kgx5 days (ip). Another derivative of this compound namely 1-(4-chlorophenyl)-3-hydroxymethyl-9H-pyrido[3,4-b]indole (5a) exhibited highest activity against L. carinii at 30 mg/kg x 5 days (ip) and against B. malayi at 50 mg/kg x 5 days (ip) or at 200 mg/ kgx5 days (po). (C) 1999 Elsevier Science Ltd. All rights reserved.