cis-p-tolyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester | 238428-12-1

• 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: cis-p-tolyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester
• 英文别名: (1S,3S)-methyl 1-(4-methylphenyl)-2,3,4,9-tetrahydo-1H-pyrido[3,4-b]indole-3-carboxylate；methyl (1S,3S)-1-(4-methylphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 238428-12-1
• 化学式: C₂₀H₂₀N₂O₂
• 分子量: 320.391
• InChiKey: BEEVAEJHPKFYMA-ROUUACIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  cis-p-tolyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylic acid methyl ester 在 sulfur 、 一水合肼 作用下， 以 乙醇 、 xylene 为溶剂， 生成 1-(p-tolyl)-9H-pyrido[3,4-b]indole-3-carbonylhydrazide
  参考文献：
  名称：

  Potent 1,3-disubstituted-9H-pyrido[3,4-b]indoles as new lead compounds in antifilarial chemotherapy1CDRI Communication No. 5795.1

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(99)00050-4
• 作为产物：
  描述：

  L-色氨酸 在 氯化亚砜 、 sodium carbonate 作用下， 以 甲醇 为溶剂， 生成 cis-p-tolyl-2,3,4,9-tetrahydro-1H-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 chemotherapy1CDRI Communication No. 5795.1

  摘要：

  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.

  DOI：

  10.1016/s0968-0896(99)00050-4

文献信息

• Identification of Novel Amino Acid Derived CCK-2R Antagonists As Potential Antiulcer Agent: Homology Modeling, Design, Synthesis, and Pharmacology
  作者：Amit K. Gupta、Kanika Varshney、Neetu Singh、Vaibhav Mishra、Mridula Saxena、Gautam Palit、Anil K. Saxena

  DOI：10.1021/ci3003655

  日期：2013.1.28

  homology model of CCK-2R using human A2a adenosine receptor and the resolved NMR based structure of the third extracellular loop of the CCK-2R as templates. Further in order to identify novel antiulcer agents, rational designing have been performed utilizing the substructure of a well-known CCK-2R antagonist benzotript as a lead molecule and submitted to the combined docking and simulation studies. This

  本研究使用人类A 2a重新研究了CCK-2R的三维（3D）同源性模型腺苷受体和CCK-2R第三细胞外环的基于NMR的解析结构作为模板。此外，为了鉴定新的抗溃疡剂，已经利用公知的CCK-2R拮抗剂苯并三联体的亚结构作为前导分子进行了合理的设计，并进行了联合的对接和模拟研究。这导致了对小分子CCK-2R拮抗剂构象异构体的基本结构要求以及结合模式的变化的理解。在下一步中，进行这些分子的每种构型异构体的制备并提交其体外活性，然后在体内筛选成抗溃疡大鼠模型。6a是一种口服活性安全候选分子，具有比众所周知的苯并三唑更好的抗溃疡特性。
• Synthesis and biological evaluation of indolyl glyoxylamides as a new class of antileishmanial agents
  作者：Shikha S. Chauhan、Leena Gupta、Monika Mittal、Preeti Vishwakarma、Suman Gupta、Prem M.S. Chauhan

  DOI：10.1016/j.bmcl.2010.08.119

  日期：2010.11

  A series of indolylglyoxylamide derivatives have been synthesized and evaluated in vitro against amastigote form of Leishmania donovani. Compound 8c has been identified as the most active analog of the series with IC(50) value of 5.17 mu M and SI value of 31.48, and is several folds more potent than the standard drugs sodium stilbogluconate and pentamidine. (C) 2010 Elsevier Ltd. All rights reserved.
• Synthesis and cytotoxicity evaluation of (tetrahydro-β-carboline)-1,3,5-triazine hybrids as anticancer agents
  作者：Ravi Kumar、Leena Gupta、Pooja Pal、Shahnawaz Khan、Neetu Singh、Sanjay Babu Katiyar、Sanjeev Meena、Jayanta Sarkar、Sudhir Sinha、Jitendra Kumar Kanaujiya、Savita Lochab、Arun Kumar Trivedi、Prem M.S. Chauhan

  DOI：10.1016/j.ejmech.2010.02.001

  日期：2010.6

  A series of tetrahydro-beta-carbolines and 1,3,5-triazine hybrids have been synthesized and evaluated for their cytotoxicity against a panel of eight human cancer cell lines and normal human fibroblasts (NIH3T3). It led us to discovery of racemic compounds 69, 71 and 75, which are selectively cytotoxic towards KB (oral cancer) cell line with IC(50) values of 1058, 664 7 and 122.2 nM, respectively, while their enantiopure forms are less active and not selective. Enantiopure compound 42 showed 2 5 times more selectivity towards MCF7 cells over normal fibroblast NIH3T3 cells with an IC(50) value of 740 nM, also arrests cell cycle in G(1) phase and induces apoptosis in MCF7 and MDA MB231cell lines.
• Water as an efficient medium for the synthesis of tetrahydro-β-carbolines via Pictet–Spengler reactions
  作者：Biswajit Saha、Sunil Sharma、Devesh Sawant、Bijoy Kundu

  DOI：10.1016/j.tetlet.2006.12.112

  日期：2007.2

  A mild and efficient protocol for the Pictet-Spengler reaction in water using an acid catalyst has been described. The condensation of tryptophan, tryptamine, and N-b-benzyl tryptophan with different aldehydes having both electron-withdrawing and -donating substituents in the presence of a catalytic amount of TFA in water furnished tetrahydro-beta-carbolines in good isolated yields. A salient feature of the water mediated Pictet-Spengler reaction was the general trend observed during the condensation of Trp-OMe and aryl/aliphatic aldehydes furnishing diastereomeric mixtures with a preference for the cis-isomer. (c) 2007 Elsevier Ltd. All rights reserved.