(1R,3S)-methyl-1-(thiophen-2-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate | 238428-23-4

• 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: (1R,3S)-methyl-1-(thiophen-2-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• 英文别名: methyl (1R,3S)-1-(thiophene-2-yl)-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate；trans-3-carboxy-1-thienyltetrahydro-β-carboline；methyl (1R,3S)-1-thiophen-2-yl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 238428-23-4
• 化学式: C₁₇H₁₆N₂O₂S
• 分子量: 312.392
• InChiKey: KYUMJWNDZQTKTB-BBRMVZONSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  82.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1R,3S)-methyl-1-(thiophen-2-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate 在 lithium aluminium tetrahydride 、 sulfur 作用下， 以 四氢呋喃 、 xylene 为溶剂， 生成 [1-(thiophene-2-yl)-9H-β-carboline-3-yl]methanol
  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 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 72.0h， 生成 (1R,3S)-methyl-1-(thiophen-2-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  Sharma; Bhaduri, Susmita; Kaur, Gurpreet, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 12, p. 2710 - 2715

  摘要：

  DOI：

文献信息

• Design, synthesis and bio-evaluation of C-1 alkylated tetrahydro-β-carboline derivatives as novel antifungal lead compounds
  作者：Rahul Singh、Aanchal Jaisingh、Indresh K. Maurya、Deepak B. Salunke

  DOI：10.1016/j.bmcl.2019.126869

  日期：2020.2

  prominent antimicrobial activity of β-carboline derivatives, a set of C1 alkylated tetrahydro-β-carboline derivatives were proposed to be active against fungi. To validate and confirm the role of suitable alkyl chains linked to a β-carboline scaffold, few related analogues having C1 aryl substituents were also synthesized in one step via classic Pictet-Spengler reaction. The synthesized library was evaluated

  抗真菌剂的领域已经变得静止，病原体对抗药性的发展以及市售药物的有限临床功效要求不断开发新的抗真菌剂。发现与各种不同的杂环连接的特定长度的烃链的存在是各种抗真菌先导化合物的重要结构特征。基于β-咔啉衍生物的显着抗菌活性，提出了一组具有C1烷基化的四氢-β-咔啉衍生物对真菌具有活性。为了验证并确认连接至β-咔啉骨架的合适烷基链的作用，还通过经典的Pictet-Spengler反应一步合成了一些具有C1芳基取代基的相关类似物。评价合成文库对白色念珠菌的抗真菌活性。krusei，C。parapsilosis，C。kefyr，C。glabrata，C.tropicis和C.neoformans。具有八个碳原子的n-烷基链的文库成员之一（化合物12c）表现出对光滑杯状念珠菌和C. kefyr的有效抗真菌活性。具有选择性毒性的铅化合物还显示出显着的协同作用，可将抗真菌药物的效力提高多达10倍。时间杀灭动
• Diastereoselective Synthesis of Bridged Polycyclic Alkaloids via Tandem Acylation/Intramolecular Diels–Alder Reaction
  作者：Chih-Hau Chen、Gorakh S. Yellol、Cheng-Hsun Tsai、Prashant B. Dalvi、Chung-Ming Sun

  DOI：10.1021/jo401364s

  日期：2013.10.4

  A mild and efficient stereoselective synthesis of hexacyclic indole alkaloids with a tetrahydro-β-carboline motif has been developed by utilizing the Pictet–Spengler reaction and tandem N-acylation followed by intramolecular Diels–Alder cyclization. Initially, a diene unit was installed in the tetrahedron β-carboline skeleton through Pictet–Spengler cyclization of the corresponding aldehyde with tryptophan

  利用Pictet-Spengler反应和串联N-酰化，随后进行分子内Diels-Alder环化，已开发出温和而高效的立体选择性合成具有四氢-β-咔啉基团的六环吲哚生物碱。最初，通过色氨酸酯的相应醛的Pictet-Spengler环化反应，在四面体β-咔啉骨架中安装了二烯单元。亲二烯体部分由N引入-四氢-β-咔啉的酰化。连续的[4 + 2]分子内Diels-Alder环加成反应的亲二烯体和含共轭二烯的中间体，这些中间体提供了具有高非对映选择性的桥接多环杂环。该策略的关键特征是形成四个新的环，五个新的共价键和五个具有出色立体选择性的新手性中心。产物的非对映选择性形成归因于通过手性氨基酸的分子内手性转移。X射线晶体学研究证实了该串联反应的立体选择性结果。
• Liquid-phase parallel synthesis of tetrahydro-β-carbolines
  作者：Wen-Ben Yeh、Mei-Jung Lin、Chung-Ming Sun

  DOI：10.1016/s0040-4039(03)01100-6

  日期：2003.6

  Parallel synthesis of beta-carbolines on soluble polyethylene glycol (PEG-OH) support is demonstrated. One-pot condensation of polymer-bound tryptophan residues with various aldehydes and ketones has been carried out in the presence of p-TSA as a catalyst to deliver immobilized 1,2,3,4-tetrahydro-beta-carbolines. Subsequent disengagement of the appendant from the polymer support afforded the desired products in good yield and acceptable purity. (C) 2003 Elsevier Science Ltd. All rights reserved.
• 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.
• Sharma; Bhaduri, Susmita; Kaur, Gurpreet, Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 2006, vol. 45, # 12, p. 2710 - 2715
  作者：Sharma、Bhaduri, Susmita、Kaur, Gurpreet

  DOI：——

  日期：——