(S)-tert-butyl 3-((S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-ylcarbamoyl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate | 900865-82-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (S)-tert-butyl 3-((S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-ylcarbamoyl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate
• 英文别名: N-((3S)-2-N-Boc-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxyl)-L-tryptophan methyl ester；N-[(3S)-2-Boc-1,2,3,4-tetrahydro-β-carboline-3-carbonyl]-L-tryptophane methyl ester；tert-butyl (3S)-3-[[(2S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-yl]carbamoyl]-1,3,4,9-tetrahydropyrido[3,4-b]indole-2-carboxylate
• CAS: 900865-82-9
• 化学式: C₂₉H₃₂N₄O₅
• 分子量: 516.597
• InChiKey: QULCOOMRHIVRLT-ZCYQVOJMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  38
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  117
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-tert-butyl 3-((S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-ylcarbamoyl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate 在 N-甲基吗啉 、 盐酸 、 sodium hydroxide 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 氯仿 、 乙酸乙酯 为溶剂， 反应 19.17h， 生成 (3S,12aS)-3-indol-3-ylmethyl-1,4-dioxo-1,2,3,4,6,7,12,12a-octahydropyrazino[2',1':6,1]pyrido[3,4-b]indole
  参考文献：
  名称：

  Toward breast cancer resistance protein (BCRP) inhibitors: design, synthesis of a series of new simplified fumitremorgin C analogues

  摘要：

  In this study, we report the design and synthesis of a series of new simplified fumitremorgin C analogues. The preliminary biological study indicated some of these simplified fumitremorgin C might be developed into breast cancer resistance inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.04.045
• 作为产物：
  描述：

  (S)-2,3,4,9-四氢-1H-吡啶[3,4-b]吲哚-3-羧酸 在 N-甲基吗啉 、 1-羟基苯并三唑一水物 、 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-tert-butyl 3-((S)-3-(1H-indol-3-yl)-1-methoxy-1-oxopropan-2-ylcarbamoyl)-3,4-dihydro-1H-pyrido[3,4-b]indole-2(9H)-carboxylate
  参考文献：
  名称：

  Synthesis of new class dipeptide analogues with improved permeability and antithrombotic activity

  摘要：

  3-(S)-1,2,3,4-Tetrahydro-beta-carboline-3-carboxylic acid isolated from A. Chinese G. Don was found to possess moderate anti-aggregation activity, but with poor bioavailability. To improve its pharmacological property, we designed and synthesized a series of novel dipeptide analogues by incorporating tetrahydro-beta-carboline-3-carboxylic acid skeleton as an amino acid surrogate (*Trp). It turned out these dipeptide analogues exhibited good membrane permeability based on in vitro Caco-2 cell monolayers permeability assay. As a result, the overall biological properties of these molecules were significantly improved depending on the nature of the amino acid residues introduced onto the 3-position of the tetrahydro-beta-carboline moiety. It was very interesting to notice that these dipeptide analogues (5b,c,h,i,n,o,p,q) displayed a remarkable dual antiaggregatory activity in both of ADP- and PAF-induced platelet aggregation assay, and their aggregation response was significantly higher than that of aspirin (p < 0.01). In addition, these dipeptide analogues were observed for the dose-dependent antithrombotic effect using in vivo rat arterial thrombosis model. The potency of antithrombotic activity of 5h,i,n,p was significantly higher than that of aspirin (n = 12, p < 0.01) at equal dose (5 mu mol/kg). (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.03.026

文献信息

• Synthesis of new class dipeptide analogues with improved permeability and antithrombotic activity
  作者：Ming Zhao、Lanrong Bi、Wei Bi、Chao Wang、Zhe Yang、Jingfang Ju、Shiqi Peng

  DOI：10.1016/j.bmc.2006.03.026

  日期：2006.7.15

  3-(S)-1,2,3,4-Tetrahydro-beta-carboline-3-carboxylic acid isolated from A. Chinese G. Don was found to possess moderate anti-aggregation activity, but with poor bioavailability. To improve its pharmacological property, we designed and synthesized a series of novel dipeptide analogues by incorporating tetrahydro-beta-carboline-3-carboxylic acid skeleton as an amino acid surrogate (*Trp). It turned out these dipeptide analogues exhibited good membrane permeability based on in vitro Caco-2 cell monolayers permeability assay. As a result, the overall biological properties of these molecules were significantly improved depending on the nature of the amino acid residues introduced onto the 3-position of the tetrahydro-beta-carboline moiety. It was very interesting to notice that these dipeptide analogues (5b,c,h,i,n,o,p,q) displayed a remarkable dual antiaggregatory activity in both of ADP- and PAF-induced platelet aggregation assay, and their aggregation response was significantly higher than that of aspirin (p < 0.01). In addition, these dipeptide analogues were observed for the dose-dependent antithrombotic effect using in vivo rat arterial thrombosis model. The potency of antithrombotic activity of 5h,i,n,p was significantly higher than that of aspirin (n = 12, p < 0.01) at equal dose (5 mu mol/kg). (c) 2006 Elsevier Ltd. All rights reserved.
• Methyl (11a<i>S</i>)-1,2,3,5,11,11a-Hexahydro-3,3-dimethyl-1-oxo-6<i>H</i>-imidazo-[3′,4′:1,2]pyridin[3,4-<i>b</i>]indol-2-Substituted Acetates: Synthesis and Three-Dimensional Quantitative Structure−Activity Relationship Investigation as a Class of Novel Vasodilators
  作者：Jiawang Liu、Ming Zhao、Guohui Cui、Xiaoyi Zhang、Jun Wang、Shiqi Peng

  DOI：10.1021/jm800249j

  日期：2008.8.1

  To find selective inhibitor of phosphodiesterase type 5 (PDE5), the essential structure elements of clinically used drugs sildenafil, vardenafil, and tadalafil were combined and a tetracyclic parent was constructed to which in 2-positions substituted acetic acid methylesters were introduced to form 17 novel vasodilators, methyl (11aS)-1,2,3,5,11,11a-hexahydro-3,3-dimethyl-1-oxo-6H-imidazo[3',4':1,2]- pyridin[3,4-b]indol-2-substituted acetates. By molecular field analysis (MFA), an equation of three-dimensional quantitative structure-activity relationship (3D QSAR) was established, which not only revealed the dependence of the in vitro vasorelaxation activities on the structures but also pointed out the way to design new lead compounds properly. Docking these novel vasodilators into the hydrophobic pocket of phosphodiesterase type 5 (PDE5) revealed that their adaptabilities to this pocket did significantly affect on their vasorelaxation activity. Actually, the docking adaptabilities of these novel vasodilators to PDE5 were consistent with the conformational requirements of them to MFA and with the crystal conformation of two representatives.
• Toward breast cancer resistance protein (BCRP) inhibitors: design, synthesis of a series of new simplified fumitremorgin C analogues
  作者：Guofeng Wu、Jiawang Liu、Lanrong Bi、Ming Zhao、Chao Wang、Michèle Baudy-Floc'h、Jingfang Ju、Shiqi Peng

  DOI：10.1016/j.tet.2007.04.045

  日期：2007.6

  In this study, we report the design and synthesis of a series of new simplified fumitremorgin C analogues. The preliminary biological study indicated some of these simplified fumitremorgin C might be developed into breast cancer resistance inhibitors. (c) 2007 Elsevier Ltd. All rights reserved.