1-[4-(N,N-dimethylamino)phenyl]-β-carboline-3-carboxylic acid methyl ester | 1085709-13-2

• 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-(N,N-dimethylamino)phenyl]-β-carboline-3-carboxylic acid methyl ester
• 英文别名: methyl 1-(4-dimethylamino)-9H-pyrido[3,4-b]indole-3-carboxylate；methyl 1-[4-(dimethylamino)phenyl]-9H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 1085709-13-2
• 化学式: C₂₁H₁₉N₃O₂
• 分子量: 345.401
• InChiKey: PTPKWAJKSSPKGY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-[4-(N,N-dimethylamino)phenyl]-β-carboline-3-carboxylic acid methyl ester 在 一水合肼 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  新型杂种β-咔啉-4-噻唑烷酮类化合物的合成和评价作为潜在的抗肿瘤和抗病毒药

  摘要：

  合成了一系列新颖的杂种β-咔啉-4-噻唑烷酮，并评估了其对人癌细胞的体外抗肿瘤活性以及对单纯疱疹病毒1型（HSV-1）的抗病毒活性。从N' - （咪唑烷-2-亚基-4-噻唑烷酮） - β咔啉-3-碳酰肼系列（9-11），Ç ompounds 9C和11d中是最活跃的，表现出生长抑制50％（GI 50）的值小于对于所有测试的细胞系，均大于5μM 化合物9c中，轴承4 -二甲氨基苯基在C-1 β选择-咔啉来进行有关细胞死亡和细胞周期图的进一步研究，重点是人肾腺癌细胞系786-0。用25μM的化合物9c处理在处理15小时后会诱导细胞死亡，其特征在于磷脂酰丝氨酸的暴露和膜完整性的丧失。此外，用12.5μM的处理可促进亚G1阻滞，这表明细胞死亡。N-（2-取代-芳基-4-噻唑烷酮）-β-咔啉-3-羧酰胺系列（18-23）的衍生物显示出对神经胶质瘤（U251）和卵巢癌（OVCAR-3）的强活性和高选择

  DOI：

  10.1016/j.ejmech.2016.10.018
• 作为产物：
  描述：

  1-(4-dimethylamino-phenyl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester 在 sulfur 作用下， 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 48.0h， 生成 1-[4-(N,N-dimethylamino)phenyl]-β-carboline-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis, Antileishmanial Activity and Spin Labeling EPR Studies of Novel β-Carboline-Oxazoline and β-Carboline-Dihydrooxazine Derivatives

  摘要：

  A series of novel 1-(substituted-phenyl)-3-(4,5-dihydro-1,3-oxazol-2-yl)-9H-beta-carboline (8a-8i) and 1-(substituted-phenyl)-3-(5,6-dihydro-4H-1,3-oxazin-2-yl)-9H-beta-carboline (9a-9h) derivatives. as well as their respective N-(chloroalkyl)-1-(substituted-phenyl)-9H-beta-carboline-3-carboxamide precursors (6a-6i and 7a-7h), were synthesized and evaluated for their in vitro antileishmanial activity against promastigote and intracellular amastigote forms of Leishmania amazonensis. Compounds 8d. 8i, 9e and 9h exhibited significant activity for both promastigote and amastigote forms, with IC50 (50% inhibitory concentration) values ranging from 2.9 to 23.0 mu M. In addition, spin label electron paramagnetic resonance (EPR) spectroscopy studies were carried out for the most active compounds against L amazonensis promastigotes. The studies indicated that the tested compounds cause strong stiffness in the parasite plasma membrane and are capable of inducing internal metalloproteins oxidation of the parasite, resulting in their cross-linking to skeletal proteins. Compounds 8d and 8i produced the largest effect, showing that the presence of oxazoline group at C-3 of beta-carboline nucleus is important for antileishmanial activity.

  DOI：

  10.21577/0103-5053.20200003

文献信息

• Synthesis and antitumor activity of β-carboline 3-(substituted-carbohydrazide) derivatives
  作者：Valéria Aquilino Barbosa、Anelise S. Nazari Formagio、Franciele Cristina Savariz、Mary Ann Foglio、Humberto Moreira Spindola、João Ernesto de Carvalho、Emerson Meyer、Maria Helena Sarragiotto

  DOI：10.1016/j.bmc.2011.08.059

  日期：2011.11

  synthesized and evaluated for their antitumor activity against eight human cancer cell lines. The β-carboline N-(substituted-benzylidene)carbohydrazides showed, in general, a greater antitumor activity than their N-(alkylidene)carbohydrazide analogues. The N9-methylation of β-carboline N-(substituted-benzylidene) carbohydrazides resulted in a decrease of antitumor activity. Among compounds tested, the b

  合成了一系列在C-3处带有取代的碳酰肼部分的β-咔啉衍生物，并评估了其对八种人类癌细胞系的抗肿瘤活性。通常，β-咔啉N-（取代的亚苄基）碳酰肼显示出比其N-（亚烷基）碳酰肼类似物更大的抗肿瘤活性。β-咔啉N-（取代的亚苄基）碳酰肼的N 9甲基化导致抗肿瘤活性降低。在所测试的化合物中，苄基碳酰肼3，4，11，13，16，21和22是最活跃的，具有IC对于八种肿瘤细胞系中的六种，有50种小于10μM。衍生物4对所有测试的细胞系表现出最显着的活性，对肾脏（786-0）细胞系具有显着的细胞毒性（IC 50  = 0.04μM）。在Ehrlich实体癌测定中测定化合物4的体内抗肿瘤活性。
• Iodine-catalyzed one-pot decarboxylative aromatization of tetrahydro-β-carbolines
  作者：Ramu Meesala、Ahmad Saifuddin Mohamad Arshad、Mohd Nizam Mordi、Sharif Mahsufi Mansor

  DOI：10.1016/j.tet.2016.10.069

  日期：2016.12

  A synthetic strategy was developed for the preparation of β-carbolines by one-pot decarboxylation and aromatization of tetrahydro-β-carboline-3-carboxylic acids by employing 10 mol% of iodine in presence of oxidant aqueous H2O2. The method was also successfully extended for the aromatization of tetrahydro-β-carboline-3-methyl esters. The utility of the method was demonstrated in the synthesis of β-carboline

  合成策略用于制备β咔啉通过一锅脱羧和四氢β咔啉-3-羧酸的芳构化通过采用10mol％的碘在氧化剂水溶液H的存在开发2 Ò 2。该方法也成功地扩展到四氢-β-咔啉-3-甲基酯的芳构化。该方法的实用性在β-咔啉生物碱正丹烷，丹参烷和芥子气素N的合成中得到了证明。
• Synthesis and antitumoral activity of novel 3-(2-substituted-1,3,4-oxadiazol-5-yl) and 3-(5-substituted-1,2,4-triazol-3-yl) β-carboline derivatives
  作者：Anelise S. Nazari Formagio、Lilian T. Düsman Tonin、Mary Ann Foglio、Christiana Madjarof、João Ernesto de Carvalho、Willian Ferreira da Costa、Flávia P. Cardoso、Maria Helena Sarragiotto

  DOI：10.1016/j.bmc.2008.10.008

  日期：2008.11

  Several novel 1-substituted-phenyl beta-carbolines bearing the 2-substituted-1,3,4-oxadiazol-5-yl and 5-substituted-1,2,4-triazol-3-yl groups at C-3 were synthesized and evaluated for their in vitro anticancer activity. The assay results pointed thirteen compounds with growth inhibition effect (GI(50) < 100 mu M) for all eight different types of human cancer cell lines tested. The b-carbolines 7a and 7h, bearing the 3-(2-metylthio-1,3,4-oxadiazol-5-yl) group, displayed high selectivity and potent anticancer activity against ovarian cell line with GI50 values lying in the nanomolar concentration range (GI(50) = 10 nM for both compounds). The 1-(N,N-dimethylaminophenyl)-3-(5-thioxo-1,2,4-triazol-3-yl) beta-carboline (8g) was the most active compound, showing particular effectiveness on lung (GI(50) = 0.06 mu M), ovarian and renal cell lines. The potent anticancer activity presented for synthesized compounds 7a, 7h, and 8g, together with their easiness of synthesis, makes these compounds promising anticancer agents. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis and anti-Mycobacterium tuberculosis activity of imide-β-carboline and carbomethoxy-β-carboline derivatives
  作者：Mariana Aparecida Lopes-Ortiz、Manuela Ribeiro Panice、Eduardo Borges de Melo、João Paulo Ataide Martins、Vanessa Pietrowski Baldin、Cláudia Terêncio Agostinho Pires、Katiany Rizzieri Caleffi-Ferracioli、Vera Lúcia Dias Siqueira、Regiane Bertin de Lima Scodro、Maria Helena Sarragiotto、Rosilene Fressatti Cardoso

  DOI：10.1016/j.ejmech.2019.111935

  日期：2020.2

  A series of methyl beta-carboline carboxylates (2a-g) and of imide-O-carboline derivatives containing the phthalimide (4a-g), maleimide (5b, g) and succinimide (6b, e, g) moiety were synthesized, and evaluated for their activity against Mycobacterium tuberculosis H(37)Rv. The most active beta-carboline derivatives against the reference strain were assayed for their cytotoxicity and the activity against resistant M. tuberculosis clinical isolates. Farther, structure-activity relationship (SAR) studies were carried out using the three and four-dimensional approaches for starting to understand the way of beta-carboline activity in M. tuberculosis. All 19 beta-carboline derivatives were assayed, firstly, by determining the minimum inhibitory concentration (MIC) using resazurin microtiter assay plate (REMA) in M. tuberculosis H 37 Rv. Then, five derivatives (2c, 4a, 4e, 4g, 6g), which showed MIC <= 125 mu g/mL, were assayed in nine resistant M. tuberculosis clinical isolates (five MDR, three isoniazid monoresistant and one isoniazid plus streptomycin resistant). The MIC values against the resistant clinical isolates ranged from 31.25 to >250 mu g/mL. All five derivatives were non-cytotoxic to the VERO cell line, determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, at the tested concentration (selectivity index ranged from <1.74 to 14.4). Our study demonstrated that (2c) and (6g) derivatives had better antiM. tuberculosis activity, especially against resistant clinical isolates, what makes them scaffold candidates for further investigations about their anti-tuberculosis activity. The SAR study conducted with the 19 beta-carboline derivatives showed the importance of steric effects for the synthesized beta-carbolines against M tuberculosis, and these models can be used for future proposition of new derivatives, increasing the chances of obtaining potentially anti-tuberculosis compounds. (C) 2019 Elsevier Masson SAS. All rights reserved.