1-(4-hydroxy-3-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide | 1085709-10-9

• 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-hydroxy-3-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide
• CAS: 1085709-10-9
• 化学式: C₁₉H₁₆N₄O₃
• 分子量: 348.361
• InChiKey: WVEZMOTUXGTPLF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  113.26
• 氢给体数：
  4.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  苯酐 、 1-(4-hydroxy-3-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide 以 5,5-dimethyl-1,3-cyclohexadiene 为溶剂， 反应 24.0h， 以83%的产率得到1-(3-methoxy-4-hydroxyphenyl)-β-carboline-3-N-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)carboxamide
  参考文献：
  名称：

  Synthesis and anti-Mycobacterium tuberculosis activity of imide-β-carboline and carbomethoxy-β-carboline derivatives

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2019.111935
• 作为产物：
  描述：

  methyl 1-(4-hydroxy-3-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carboxylate 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 48.0h， 生成 1-(4-hydroxy-3-methoxyphenyl)-9H-pyrido[3,4-b]indole-3-carbohydrazide
  参考文献：
  名称：

  Synthesis and anti-Mycobacterium tuberculosis activity of imide-β-carboline and carbomethoxy-β-carboline derivatives

  摘要：

  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.

  DOI：

  10.1016/j.ejmech.2019.111935

文献信息

• 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.