1-(2-Fluoro-phenyl)-9H-β-carboline-3-carboxylic acid methyl ester | 223690-89-9

• 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-(2-Fluoro-phenyl)-9H-β-carboline-3-carboxylic acid methyl ester
• 英文别名: methyl 1-(2-fluorophenyl)-9H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 223690-89-9
• 化学式: C₁₉H₁₃FN₂O₂
• 分子量: 320.323
• InChiKey: KDJNQJRWHXFODX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  55
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-(2-Fluoro-phenyl)-9H-β-carboline-3-carboxylic acid methyl ester 在 ammonium hydroxide 作用下， 以 甲醇 为溶剂， 反应 8.0h， 生成 1-(2-fluorophenyl)-9H-pyrido[3,4-b]indole-3-carboxamide
  参考文献：
  名称：

  Potent 1,3-Disubstituted-9H-pyrido[3,4-b]indoles as New Lead Compounds in Antifilarial Chemotherapy^,

  摘要：

  Substituted 9H-pyrido[3,4-b]indoles (beta-carbolines), identified in our laboratory as potential pharmacophores for designing macrofilaricidal agents, have been explored further for identifying the pharmacophore responsible for the 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-carboxylate derivatives (3-7). The macrofilaricidal activity was initially evaluated in vivo against Acanthoeilonema viteae. Among all the synthesized compounds, only 12 compounds, namely 3a, 3c, 3d, 3f, 4c, 4d, 4f, 5a, 6f, 6h, 6i, and 7h, have exhibited either > 90% micro- or macrofilaricidal activity or sterlization 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 has been discussed. It has been observed that the presence of a carbomethoxy at position 3 and an aryl substituent at position 1 in beta-carbolines effectively enhances antifilarial activity particularly against A. viteae. Among the various compounds screened, methyl 1-(4-methylphenyl)-9H-pyrido[3,4-b] indole-3-carboxylate (4c) has shown the highest adulticidal activity and methyl 1-(4-chlorophenyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate (3a) has shown the highest microfilaricidal action against A. viteae at 50 mg/kg x 5 days (ip). Another derivative of this compound, namely 1-(4-chlorophenyl)-3-(hydroxymethyl)-9H-pyrido[3,4-b]indole (5a), exhibited the highest activity against L. carinii at 30 mg/kg x 5 days tip! and against B. malayi at 50 mg/kg x 5 days tip) or at 200 mg/kg x 5 days (po).

  DOI：

  10.1021/jm9800705
• 作为产物：
  描述：

  L-色氨酸甲酯盐酸盐 在 sodium carbonate 、 sulfur 作用下， 以 甲醇 、 xylene 为溶剂， 反应 8.0h， 生成 1-(2-Fluoro-phenyl)-9H-β-carboline-3-carboxylic acid methyl ester
  参考文献：
  名称：

  Potent 1,3-Disubstituted-9H-pyrido[3,4-b]indoles as New Lead Compounds in Antifilarial Chemotherapy^,

  摘要：

  Substituted 9H-pyrido[3,4-b]indoles (beta-carbolines), identified in our laboratory as potential pharmacophores for designing macrofilaricidal agents, have been explored further for identifying the pharmacophore responsible for the 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-carboxylate derivatives (3-7). The macrofilaricidal activity was initially evaluated in vivo against Acanthoeilonema viteae. Among all the synthesized compounds, only 12 compounds, namely 3a, 3c, 3d, 3f, 4c, 4d, 4f, 5a, 6f, 6h, 6i, and 7h, have exhibited either > 90% micro- or macrofilaricidal activity or sterlization 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 has been discussed. It has been observed that the presence of a carbomethoxy at position 3 and an aryl substituent at position 1 in beta-carbolines effectively enhances antifilarial activity particularly against A. viteae. Among the various compounds screened, methyl 1-(4-methylphenyl)-9H-pyrido[3,4-b] indole-3-carboxylate (4c) has shown the highest adulticidal activity and methyl 1-(4-chlorophenyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate (3a) has shown the highest microfilaricidal action against A. viteae at 50 mg/kg x 5 days (ip). Another derivative of this compound, namely 1-(4-chlorophenyl)-3-(hydroxymethyl)-9H-pyrido[3,4-b]indole (5a), exhibited the highest activity against L. carinii at 30 mg/kg x 5 days tip! and against B. malayi at 50 mg/kg x 5 days tip) or at 200 mg/kg x 5 days (po).

  DOI：

  10.1021/jm9800705

文献信息

• Synthesis and evaluation of novel hybrids β -carboline-4-thiazolidinones as potential antitumor and antiviral agents
  作者：Valéria Aquilino Barbosa、Paula Baréa、Renata Sespede Mazia、Tania Ueda-Nakamura、Willian Ferreira da Costa、Mary Ann Foglio、Ana Lucia T. Goes Ruiz、João Ernesto de Carvalho、Débora Barbosa Vendramini–Costa、Celso Vataru Nakamura、Maria Helena Sarragiotto

  DOI：10.1016/j.ejmech.2016.10.018

  日期：2016.11

  -carboxamide series (18–23) showed a potent activity and high selectivity for glioma (U251) and ovarian (OVCAR-3) cancer cell lines. Also, some β-carboline-4-thiazolidinone hybrids showed potent antiviral activity against Herpes simplex virus type-1. The N-(2-substituted-aryl-4-thiazolidinone)-carboxamide moiety in 18, 19 and 22 confer a potent anti-HSV-1 activity for these derivatives, which presented

  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
• Synthesis, Antileishmanial Activity and Spin Labeling EPR Studies of Novel β-Carboline-Oxazoline and β-Carboline-Dihydrooxazine Derivatives
  作者：Paula Baréa、Jéssica de Paula、Laís Alonso、Aline de Oliveira、Willian da Costa、Antonio Alonso、Celso Nakamura、Maria Sarragiotto

  DOI：10.21577/0103-5053.20200003

  日期：——

  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.
• 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.
• Potent 1,3-Disubstituted-9<i>H</i>-pyrido[3,4-<i>b</i>]indoles as New Lead Compounds in Antifilarial Chemotherapy^,
  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：10.1021/jm9800705

  日期：1999.5.1

  Substituted 9H-pyrido[3,4-b]indoles (beta-carbolines), identified in our laboratory as potential pharmacophores for designing macrofilaricidal agents, have been explored further for identifying the pharmacophore responsible for the 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-carboxylate derivatives (3-7). The macrofilaricidal activity was initially evaluated in vivo against Acanthoeilonema viteae. Among all the synthesized compounds, only 12 compounds, namely 3a, 3c, 3d, 3f, 4c, 4d, 4f, 5a, 6f, 6h, 6i, and 7h, have exhibited either > 90% micro- or macrofilaricidal activity or sterlization 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 has been discussed. It has been observed that the presence of a carbomethoxy at position 3 and an aryl substituent at position 1 in beta-carbolines effectively enhances antifilarial activity particularly against A. viteae. Among the various compounds screened, methyl 1-(4-methylphenyl)-9H-pyrido[3,4-b] indole-3-carboxylate (4c) has shown the highest adulticidal activity and methyl 1-(4-chlorophenyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate (3a) has shown the highest microfilaricidal action against A. viteae at 50 mg/kg x 5 days (ip). Another derivative of this compound, namely 1-(4-chlorophenyl)-3-(hydroxymethyl)-9H-pyrido[3,4-b]indole (5a), exhibited the highest activity against L. carinii at 30 mg/kg x 5 days tip! and against B. malayi at 50 mg/kg x 5 days tip) or at 200 mg/kg x 5 days (po).