(S)-2-amino-3-(1H-indol-3-yl)-N-phenylpropanamide | 127592-76-1

• 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)-2-amino-3-(1H-indol-3-yl)-N-phenylpropanamide
• 英文别名: (2S)-2-amino-3-(1H-indol-3-yl)-N-phenylpropanamide
• CAS: 127592-76-1
• 化学式: C₁₇H₁₇N₃O
• 分子量: 279.341
• InChiKey: RZMUABAAIKIJCD-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  70.9
• 氢给体数：
  3
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (S)-2-amino-3-(1H-indol-3-yl)-N-phenylpropanamide 在 盐酸 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 四氢呋喃 、 1,4-二氧六环 为溶剂， 反应 24.0h， 生成 Boc-Pro-D-Pro-Aib-Trp-NHPh
  参考文献：
  名称：

  CATALYST FOR ASYMMETRIC HYDROGENATION AND METHOD FOR MANUFACTURING OPTICALLY ACTIVE CARBONYL COMPOUND USING THE SAME

  摘要：

  本发明提供了一种用于通过选择性不对称加氢α，β-不饱和羰基化合物制备光学活性羰基化合物的催化剂，该催化剂在反应混合物中不溶解，并提供了制备相应光学活性羰基化合物的方法。特别地，该发明提供了一种催化剂，通过选择性不对称加氢柠檬醛、香叶醛或柠檬醛制备出用作香料或芳香剂的光学活性香茅醛。该发明涉及一种用于不对称加氢α，β-不饱和羰基化合物的催化剂，包括：来自周期表第8至第10族金属中至少一种金属的粉末，或者至少一种金属负载物质，其中至少一种金属负载在一种载体上；一种光学活性肽化合物；和一种酸，还涉及使用该催化剂制备光学活性羰基化合物的方法。

  公开号：

  US20120136176A1
• 作为产物：
  描述：

  N-苄氧羰基-L-色氨酸 在 palladium on activated charcoal 氢气 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 (S)-2-amino-3-(1H-indol-3-yl)-N-phenylpropanamide
  参考文献：
  名称：

  Linear TMC-95-Based Proteasome Inhibitors

  摘要：

  We have designed and evaluated 45 linear analogues of the natural constrained cyclopeptide TMC-95A. These synthetically less demanding molecules are based on the tripeptide sequence Y-N-W of TMC-95A. Structural variations in the amino acid side chains and termini greatly influenced both the efficiency and selectivity of action on a given type of active site. Inhibition constants were submicromolar (K-i approximate to 300 nM) despite the absence of the entropically favorable constrained conformation that is characteristic of TMC-95A and its cyclic analogues. These linear compounds were readily prepared and reasonably stable in culture medium and could be optimized to inhibit one, two, or all three proteasome catalytic sites. Cytotoxicity assays performed on a series of human tumor cell lines identified the most potent inhibitors in cells.

  DOI：

  10.1021/jm0701324
• 作为试剂：
  描述：

  环己酮 、 对硝基苯甲醛 在 (S)-2-amino-3-(1H-indol-3-yl)-N-phenylpropanamide 作用下， 以 水 为溶剂， 反应 20.0h， 以44%的产率得到
  参考文献：
  名称：

  Organocatalysis of asymmetric aldol reaction in water: comparison of catalytic properties of (S)-valine and (S)-proline amides

  摘要：

  含有在N1原子上带有(S)-或(R)-α-苯乙基取代基的(S)-缬氨酰胺，能高效催化水中环状（杂环）酮与芳香醛的不对称Aldol反应，主要生成高产率（高达98%）和高对映体过量（高达94%）的Aldol反式异构体。

  DOI：

  10.1007/s11172-013-0132-z

文献信息

• Virtual Screening of Peptide and Peptidomimetic Fragments Targeted to Inhibit Bacterial Dithiol Oxidase DsbA
  作者：Wilko Duprez、Prabhakar Bachu、Martin J. Stoermer、Stephanie Tay、Róisín M. McMahon、David P. Fairlie、Jennifer L. Martin

  DOI：10.1371/journal.pone.0133805

  日期：——

  Antibacterial drugs with novel scaffolds and new mechanisms of action are desperately needed to address the growing problem of antibiotic resistance. The periplasmic oxidative folding system in Gram-negative bacteria represents a possible target for anti-virulence antibacterials. By targeting virulence rather than viability, development of resistance and side effects (through killing host native microbiota) might be minimized. Here, we undertook the design of peptidomimetic inhibitors targeting the interaction between the two key enzymes of oxidative folding, DsbA and DsbB, with the ultimate goal of preventing virulence factor assembly. Structures of DsbB - or peptides - complexed with DsbA revealed key interactions with the DsbA active site cysteine, and with a hydrophobic groove adjacent to the active site. The present work aimed to discover peptidomimetics that target the hydrophobic groove to generate non-covalent DsbA inhibitors. The previously reported structure of a Proteus mirabilis DsbA active site cysteine mutant, in a non-covalent complex with the heptapeptide PWATCDS, was used as an in silico template for virtual screening of a peptidomimetic fragment library. The highest scoring fragment compound and nine derivatives were synthesized and evaluated for DsbA binding and inhibition. These experiments discovered peptidomimetic fragments with inhibitory activity at millimolar concentrations. Although only weakly potent relative to larger covalent peptide inhibitors that interact through the active site cysteine, these fragments offer new opportunities as templates to build non-covalent inhibitors. The results suggest that non-covalent peptidomimetics may need to interact with sites beyond the hydrophobic groove in order to produce potent DsbA inhibitors.

  迫切需要具有新型骨架和新作用机制的抗菌药物来解决日益严重的抗生素抗药性问题。革兰氏阴性菌中的周质氧化折叠系统代表了抗毒力抗菌药物可能的靶点。通过针对毒力而非生存能力，可能最大限度地减少耐药性的发展和副作用（通过杀死宿主的原生微生物群）。在此，我们进行了设计，旨在针对氧化折叠的两个关键酶DsbA和DsbB之间的相互作用，设计出肽模拟物抑制剂，最终目标是阻止毒力因子组装。DsbB或肽与DsbA复合物的结构揭示了与DsbA活性位点半胱氨酸以及活性位点附近的一个疏水性凹槽的关键相互作用。目前的工作目标是发现靶向疏水性凹槽的肽模拟物，以生成非共价DsbA抑制剂。先前报道的变形杆菌DsbA活性位点半胱氨酸突变体的结构，在非共价复合物中与七肽PWATCDS结合，被用作计算机模拟筛选肽模拟物片段库的模板。得分最高的片段化合物及其九个衍生物被合成，并评估其DsbA结合和抑制作用。这些实验发现了在毫摩尔浓度下具有抑制活性的肽模拟物片段。尽管相对于通过活性位点半胱氨酸相互作用的大分子共价肽抑制剂而言，这些片段的效力较弱，但它们提供了作为构建非共价抑制剂模板的新机会。结果表明，非共价肽模拟物可能需要与疏水性凹槽以外的位点相互作用，才能产生强效的DsbA抑制剂。
• C ring may be dispensable for β-carboline: Design, synthesis, and bioactivities evaluation of tryptophan analog derivatives based on the biosynthesis of β-carboline alkaloids
  作者：Yuanqiong Huang、Yongxian Liu、Yuxiu Liu、Hongjian Song、Qingmin Wang

  DOI：10.1016/j.bmc.2015.08.016

  日期：2016.2

  According to our previous work and the latest research on the biosynthesis of β-carboline, and using the reverse thinking strategy, tryptophan, the biosynthesis precursor of β-carboline alkaloids, and their derivatives were synthesized, and their biological activities and structure–activity relationships were studied. This bioassay showed that these compounds exhibited good inhibitory activities against

  根据我们先前对β-咔啉生物合成的研究和最新研究，并采用逆向思维策略，合成了色氨酸，β-咔啉生物碱的生物合成前体及其衍生物，以及它们的生物活性和构效关系被研究了。这项生物测定结果表明，这些化合物对烟草花叶病毒（TMV）表现出良好的抑制活性。尤其是（S）-2-氨基-3-（1 H-吲哚-3-基）-N-辛基丙酰胺（4）（63.3±2.1％，67.1±1.9％，68.7±1.3％和64.5±3.1％， 500μg/ mL）在体外和体内均表现出最佳的抗病毒活性。化合物4选择该化合物用于野外试验和急性口服毒性试验，结果表明该化合物在野外具有良好的抗TMV活性，而急性口服毒性较低。我们还发现这些化合物显示出抗真菌活性和杀虫活性。
• Construction of Spirocyclic Tetrahydro-β-carbolines via Cross-Annulation of Phenols with Tryptamines in Water
  作者：Zemin Wang、Jiabin Niu、Huiying Zeng、Chao-Jun Li

  DOI：10.1021/acs.orglett.9b02613

  日期：2019.9.6

  degradation of lignin resource. Palladium-catalyzed conversion of phenols to tetrahydro-β-carboline skeletons bearing a spirocycle at the C-1 position in water is reported. Various substituted phenols are successfully cross-annulated with different tryptamines via sequential C(Ar)-O bond cleavage of phenols, C-H bond activation of tryptamines, and C-N/C-C bond formations. This method provides a new protocol

  通过降解木质素资源可以很容易地获得苯酚。据报道，钯催化的苯酚转化为在水中的C-1位带有螺环的四氢-β-咔啉骨架。通过顺序的酚的C（Ar）-O键裂解，色胺的CH键活化和CN / CC键形成，各种取代的酚可成功地与不同的色胺交叉交联。该方法提供了一种将木质素酚转化为高附加值化合物（例如天然产物可可藤）的新方案。
• Discovery of meta-sulfamoyl N-hydroxybenzamides as HDAC8 selective inhibitors
  作者：Chunlong Zhao、Jie Zang、Qin'ge Ding、Elizabeth S. Inks、Wenfang Xu、C. James Chou、Yingjie Zhang

  DOI：10.1016/j.ejmech.2018.03.002

  日期：2018.4

  research and development of histone deacetylase (HDAC) inhibitors as therapeutic agents have achieved great accomplishments, especially in oncology field, there is still an urgent need for the discovery of isoform-selective HDAC inhibitors considering the side effects caused by nonselective HDAC inhibitors. HDAC8, a unique class I zinc-dependent HDAC, is becoming a potential target in cancer and other

  在过去的十年中，尽管作为治疗剂的组蛋白脱乙酰基酶（HDAC）抑制剂的研究和开发取得了巨大的成就，尤其是在肿瘤学领域，但是考虑到由HDAC引起的副作用，仍然迫切需要发现同工型选择性HDAC抑制剂。非选择性HDAC抑制剂。HDAC8是一种独特的I类依赖锌的HDAC，正在成为癌症和其他疾病的潜在靶标。在当前的研究中，设计并合成了一系列基于N-羟基-3-氨磺酰基苯甲酰胺的HDAC8选择性抑制剂（12a-12p），其中化合物12a，12b和12c表现出有效的HDAC8抑制作用，具有两位数的纳摩尔IC 50。蛋白质印迹分析证实了其在HDAC2（> 180倍）和HDAC6（〜30倍）上的选择性和相当高的选择性。值得注意的是，12a，12b和12c对T细胞白血病细胞Jurkat，Molt-4和成神经细胞瘤细胞SK-N-BE-（2）表现出高度选择性的抗增殖活性。在众所周知的HDAC8选择性抑制剂PCI-34
• Compounds Useful as Modulators of the Proteasome Activity
  申请人：Reboud-Ravaux Michele Claude Yvonne

  公开号：US20090069222A1

  公开（公告）日：2009-03-12

  The present invention relates to the use of compounds of the following general formula (I): wherein n o is 0 or 1, and when n o is 1, X=CH 2 or X=NCH 2 C 6 H 5 ; R 1 is OH, or a OR 10 group, or a group of formula NH—(CH 2 ) n1 —R 11 ; R 2 is H, or an alkyl group, or a group of formula (CH 2 ) n2 —(CO) n3 —NR 13 R 14 ; R 3 is H, or an alkyl group; R 4 is H, or Boc, or Z; R 5 is H, or Boc, or Z; R 6 is a OR 16 group; R 7 and R 8 are H, or a halogen atom, as modulators of the proteasome activity, in the frame of the preparation of a medicament useful for the prevention or treatment of diseases wherein the proteasome is involved, or the preparation of cosmetic compositions, or of phytosanitary compositions

  本发明涉及使用以下通式（I）的化合物：其中nois为0或1，当nois为1时，X=CH2或X=NCH2C6H5; R1为OH，或OR10基团，或公式NH—（CH2）n1—R11的基团; R2为H，或烷基，或公式（CH2）n2—（CO）n3—NR13R14的基团; R3为H，或烷基; R4为H，或Boc，或Z; R5为H，或Boc，或Z; R6为OR16基团; R7和R8为H，或卤原子，作为蛋白酶体活性调节剂，用于制备用于预防或治疗蛋白酶体参与的疾病的药物，或制备化妆品组合物或植物保护组合物。