1-(thiophen-3-yl)-9H-β-carboline | 169827-90-1

• 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-(thiophen-3-yl)-9H-β-carboline
• 英文别名: 1-(thiophen-3-yl)-β-carboline；1-(thiophen-3-yl)-9H-pyrido[3,4-b]indole；1-thiophen-3-yl-9H-pyrido[3,4-b]indole
• CAS: 169827-90-1
• 化学式: C₁₅H₁₀N₂S
• 分子量: 250.324
• InChiKey: AJSHKOWTGJMCFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  56.9
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(thiophen-3-yl)-9H-β-carboline 在 sodium hydride 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 生成 1-(thiophen-3-yl)-9-(3-phenylpropyl)-2-benzyl-β-carbolinium bromide
  参考文献：
  名称：

  Synthesis and structure–activity relationships of N2-alkylated quaternary β-carbolines as novel antitumor agents

  摘要：

  A series of novel N-2-alkylated quaternary beta-carbolines was synthesized by modification of position-1, 2,7 and 9 of beta-carboline nucleus with various alkyl and arylated alkyl substituents, and their cytotoxic activities in vitro and antitumor potencies in mice were evaluated. Compound 3m was found to be the most potent antitumor agent. SARs analysis revealed that (1) the substituents in position-2 and 9 of beta-carboline nucleus played a vital role in modulation of antitumor activity; (2) the benzyl and 3-phenylpropyl substituents in position-2 and 9 of beta-carboline ring were the optimal substituents giving rise to significant antitumor agent. These compounds might be a novel promising class of antitumor agents with clinical development potential. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.031
• 作为产物：
  描述：

  3-噻吩甲醛 在 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 10.0h， 生成 1-(thiophen-3-yl)-9H-β-carboline
  参考文献：
  名称：

  单电子转移产生的超氧离子对N-杂环的脱氢作用

  摘要：

  在许多药物，天然产物和合成材料中都发现了含氮杂芳烃基序。尽管已经报道了几种通过相应的饱和杂环的脱氢合成这些化合物的优美方法，但是其中一些方法因反应时间长，苛刻的条件以及对催化剂的需求而难以获得。这项工作报告了一种新的N-杂环脱氢方法。具体而言，原位生成的O 2 .-充当N杂环底物的氧化剂，这些底物易受氢原子转移机制的氧化。这种方法为通向N-杂芳烃提供了一条通用的绿色路线。

  DOI：

  10.1002/chem.201705202

文献信息

• Dehydrogenation of N-Heterocycles by Superoxide Ion Generated through Single-Electron Transfer
  作者：Yuan-Qiong Huang、Hong-Jian Song、Yu-Xiu Liu、Qing-Min Wang

  DOI：10.1002/chem.201705202

  日期：2018.2.9

  some of the methods are hampered by long reaction times, harsh conditions, and the need for catalysts that are not readily available. This work reports a novel method for dehydrogenation of N‐heterocycles. Specifically, O2.− generated in situ acts as the oxidant for N‐heterocycle substrates that are susceptible to oxidation through a hydrogen atom transfer mechanism. This method provides a general

  在许多药物，天然产物和合成材料中都发现了含氮杂芳烃基序。尽管已经报道了几种通过相应的饱和杂环的脱氢合成这些化合物的优美方法，但是其中一些方法因反应时间长，苛刻的条件以及对催化剂的需求而难以获得。这项工作报告了一种新的N-杂环脱氢方法。具体而言，原位生成的O 2 .-充当N杂环底物的氧化剂，这些底物易受氢原子转移机制的氧化。这种方法为通向N-杂芳烃提供了一条通用的绿色路线。
• ビスβ−カルボリン系化合物、その製造方法、医薬組成物および用途
  申请人：新疆華世丹薬物研究有限責任公司

  公开号：JP2016500080A

  公开（公告）日：2016-01-07

  本発明は、ビスβ−カルボリン系化合物、その製造方法、医薬組成物および用途を開示している。具体的に、前記ビスβ−カルボリン系化合物およびその薬理上許容される塩は一般式Ｉで表され、β−カルボリン中間体とジハロゲン化アルカンの縮合によって製造される。また、本発明は、有効投与量の式Ｉで表されるビスβ−カルボリン系化合物および薬学的に許容され得る担体を含有する医薬組成物、および、このビスβ−カルボリン系化合物の抗腫瘍剤の製造における応用を開示している。かかる腫瘍には、メラノーマ、胃がん、肺がん、乳がん、腎がん、肝がん、口腔扁平上皮癌、子宮頸がん、卵巣がん、膵臓がん、前立腺がん、結腸がんが含まれる。【化１】

  This invention discloses bis β-carboline compounds, their manufacturing method, pharmaceutical compositions, and applications. Specifically, the bis β-carboline compounds and their pharmaceutically acceptable salts are represented by general formula I, and are produced by condensation of β-carboline intermediates and dihaloalkanes. Furthermore, the invention discloses pharmaceutical compositions containing the bis β-carboline compounds represented by formula I in effective dosages and pharmaceutically acceptable carriers, as well as applications in the manufacturing of antitumor agents using these bis β-carboline compounds. Such tumors include melanoma, gastric cancer, lung cancer, breast cancer, kidney cancer, liver cancer, oral squamous cell carcinoma, cervical cancer, ovarian cancer, pancreatic cancer, prostate cancer, and colon cancer.【Chemical formula 1】
• Synthesis of β-carbolines via a silver-mediated oxidation of tetrahydro-β-carbolines
  作者：Sierra D. Durham、Brianna Sierra、Maximillian J. Gomez、Jennifer K. Tran、Marc O. Anderson、Nick A. Whittington-Davis、Scott Eagon

  DOI：10.1016/j.tetlet.2017.05.098

  日期：2017.7

  The oxidation of tetrahydro-β-carbolines to β-carbolines using silver carbonate was developed as an alternative to current methods. The oxidation is extremely mild and provides the products in modest to good yields after purification. A number of functional groups are tolerated by this methodology, including reduction-sensitive groups which are often cleaved with other methods. Though the mechanism

  作为目前方法的替代方法，开发了使用碳酸银将四氢-β-咔啉氧化为β-咔啉的方法。氧化非常温和，纯化后产物收率适中，收率良好。该方法容许许多官能团，包括通常用其他方法裂解的还原敏感性基团。尽管尚未完全理解其机理，但反应在开放的烧瓶中进行，对光或湿气不敏感，并为不易通过其他方法制备的化合物提供了可行的合成途径。
• BIS-B-CARBOLINE COMPOUND AND PREPARATION METHOD, PHARMACEUTICAL COMPOSITION AND USE THEREOF
  申请人：XINJIANG HUASHIDAN PHAR MACEUTICAL RESEARCH CO., LTD

  公开号：US20160039845A1

  公开（公告）日：2016-02-11

  Disclosed in the present invention are a bis-β-carboline compound and a preparation method, a pharmaceutical composition and the use thereof. In particular, the bis-β-carboline compound and a pharmaceutical salt thereof are described as general formula I, and the bis-β-carboline compound is prepared through the condensation of β-carboline intermediate and dihaloalkane. Also disclosed in the present invention are a pharmaceutical composition comprising an effective dose of the bis-β-carboline compound as shown in formula I and a pharmaceutically acceptable carrier, and the use of the bis-β-carboline compound in preparing drugs resistant to tumours such as melanoma, stomach cancer, lung cancer, breast cancer, kidney cancer, liver cancer, oral epidermoid carcinoma, cervical cancer, ovarian cancer, pancreatic cancer, prostate cancer, and colon cancer.

  本发明公开了一种双β-咔唑化合物及其制备方法、药物组合物及其用途。其中，描述了双β-咔唑化合物及其药物盐的一般式I，双β-咔唑化合物是通过β-咔唑中间体和二卤代烷的缩合反应制备而成。本发明还公开了一种药物组合物，包括一定剂量的公式I所示的双β-咔唑化合物和药学上可接受的载体，并且公开了将双β-咔唑化合物用于制备对肿瘤具有抗药性的药物，如黑色素瘤、胃癌、肺癌、乳腺癌、肾癌、肝癌、口腔表皮癌、宫颈癌、卵巢癌、胰腺癌、前列腺癌和结肠癌。
• Discovery of 1-(Hetero)aryl-β-carboline Derivatives as IDO1/TDO Dual Inhibitors with Antidepressant Activity
  作者：Yu Zhang、Yingchun Li、Xiang Chen、Xuan Chen、Chao Chen、Li Wang、Xu Dong、Guoli Wang、Ruxin Gu、Fei Li、Feng Han、Dongyin Chen

  DOI：10.1021/acs.jmedchem.2c00677

  日期：2022.8.25

  bioinformatics analysis demonstrated that indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) are potential targets for the development of antidepressants. A series of 1-(hetero)aryl-β-carboline derivatives were designed, synthesized, and evaluated as novel IDO1/TDO dual inhibitors. Among them, compound 28 displayed potent inhibition of both IDO1 (IC50 = 3.53 μM) and TDO (IC50 = 1

  抑郁症是全球疾病和残疾负担的主要原因。色氨酸降解的犬尿氨酸途径异常与抑郁症的发病机制密切相关。综合生物信息学分析表明，吲哚胺 2,3-双加氧酶 1 (IDO1) 和色氨酸 2,3-双加氧酶 (TDO) 是开发抗抑郁药的潜在目标。一系列 1-（杂）芳基-β-咔啉衍生物被设计、合成并评估为新型 IDO1/TDO 双重抑制剂。其中，化合物28对 IDO1 (IC 50 = 3.53 μM) 和 TDO (IC 50 = 1.15 μM) 均表现出有效的抑制作用，并具有可接受的安全性和药代动力学特性。化合物28还挽救了脂多糖诱导的小鼠抑郁样行为。进一步的研究表明，28种可能具有独特的抗抑郁机制，包括抑制小胶质细胞活化、降低 IDO1 表达以及降低小鼠大脑中的促炎细胞因子和犬尿氨酸水平。总体而言，这项工作为开发IDO1/TDO双重抑制剂治疗炎症性抑郁症提供了实用指导。