(R)-tert-butyl 3-(1H-indol-3-yl)-1-oxo-1-(phenylamino)propan-2-ylcarbamate | 956489-63-7

• 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: (R)-tert-butyl 3-(1H-indol-3-yl)-1-oxo-1-(phenylamino)propan-2-ylcarbamate
• 英文别名: N-(tert-butoxycarbonyl)-N'-phenyl-D-tryptophanamide；tert-butyl-(3-(1H-indol-3-yl)-1-oxo-1-(phenylamino)propan-2-yl)carbamate；tert-butyl N-[(2R)-1-anilino-3-(1H-indol-3-yl)-1-oxopropan-2-yl]carbamate
• CAS: 956489-63-7
• 化学式: C₂₂H₂₅N₃O₃
• 分子量: 379.459
• InChiKey: HLXRUSGTIOCDDP-LJQANCHMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  83.2
• 氢给体数：
  3
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (R)-tert-butyl 3-(1H-indol-3-yl)-1-oxo-1-(phenylamino)propan-2-ylcarbamate 在 劳森试剂 、 mercury(II) diacetate 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 50.0h， 生成 (R)-tert-butyl 1-(5-(2-(1H-indol-3-yl)ethyl)-4-phenyl-4H-1,2,4-triazol-3-yl)-2-(1H-indol-3-yl)ethylcarbamate
  参考文献：
  名称：

  作为生长素释放肽受体配体的新型三唑衍生物的合成及体外和体内药理评价。1。

  摘要：

  合成了基于1,2,4-三唑结构的一系列新的生长激素促分泌素（GHS）类似物，并评估了它们在体外的结合以及刺激细胞内钙释放到LLC中表达的克隆的hGHS-1a ghrelin受体的能力。 PK-1细胞。我们已经合成了该受体的有效配体，其中一些表现为激动剂，部分激动剂或拮抗剂。在啮齿类动物皮下注射后，评估了一些最有效的化合物，例如激动剂29c（JMV2873），部分激动剂包括21b（JMV2810），拮抗剂19b（JMV2866）和19c（JMV2844），它们对食物摄入的体内活性。发现一些化合物可刺激食物摄入，如六氢萘菊酯；在该测定中，其他一些被鉴定为有效的六氢肾上腺素拮抗剂。在测试的化合物中，21b被鉴定为体外生长素释放肽受体部分激动剂，以及啮齿动物中六氢可瑞林刺激的食物摄入的有效体内拮抗剂。化合物21b对从大鼠释放GH没有影响。但是，在这一系列化合物中，不可能在体外和体内结果之间找到明确的相关性。

  DOI：

  10.1021/jm070024h
• 作为产物：
  描述：

  N-tert-butyl-N'-phenyl-S-phenylisothiourea 、 BOC-D-色氨酸 在 iron(III)-acetylacetonate 作用下， 以 异丙醇 为溶剂， 反应 72.0h， 以93%的产率得到(R)-tert-butyl 3-(1H-indol-3-yl)-1-oxo-1-(phenylamino)propan-2-ylcarbamate
  参考文献：
  名称：

  胺活化：由异硫脲和氨基酸合成N-芳基氨基酸酰胺

  摘要：

  Ñ -arylamino酰胺已经通过基于新方法被合成ñ -芳基胺活化成异硫脲，随后用下铁催化氨基酸反应。可以使用三组分反应与市售试剂叔丁基异氰化物和S-苯基苯硫代磺酸盐轻松地制备活化的N-芳基胺。相对于氨基酸（例如脂族和芳族OH，（杂）芳族NH，酰胺NH，硫醚）的侧链官能度，该方案显示出广泛的官能团相容性，并且手性氨基酸不发生差向异构化。已经研究了新酰胺合成的机理。

  DOI：

  10.1002/adsc.201700134

文献信息

• Clickable coupling of carboxylic acids and amines at room temperature mediated by SO₂F₂: a significant breakthrough for the construction of amides and peptide linkages
  作者：Shi-Meng Wang、Chuang Zhao、Xu Zhang、Hua-Li Qin

  DOI：10.1039/c9ob00699k

  日期：——

  carboxylic acids with amines was developed for the synthesis of a broad scope of amides in a simple, mild, highly efficient, robust and practical manner (>110 examples, >90% yields in most cases). The direct click reactions of acids and amines on a gram scale are also demonstrated using an extremely easy work-up and purification process of washing with 1 M aqueous HCl to provide the desired amides in

  酰胺键和肽键的构建是所有生命过程和有机合成中最基本的转变之一。结构无处不在的酰胺基序的合成对于许多重要分子（如肽，蛋白质，生物碱，药剂，聚合物，配体和农用化学品）的组装至关重要。开发了一种SO2F2介导的羧酸与胺的直接可点击偶合方法，以简单，温和，高效，稳健和实用的方式合成各种酰胺（> 110例，大多数情况下> 90％的收率） ）。
• 2-Amido-3-(1H-Indol-3-yl)-N-Substitued-Propanamides as a New Class of Falcipain-2 Inhibitors. 1. Design, Synthesis, Biological Evaluation and Binding Model Studies
  作者：Jin Zhu、Tong Chen、Lili Chen、Weiqiang Lu、Peng Che、Jin Huang、Honglin Li、Jian Li、Hualiang Jiang

  DOI：10.3390/molecules14010494

  日期：——

  The Plasmodium falciparum cysteine protease falcipain-2 (FP-2) is an important cysteine protease and an essential hemoglobinase of erythrocytic P. falciparum trophozoites. The discovery of new FP-2 inhibitors is now a hot topic in the search for potential malaria treatments. In this study, a series of novel small molecule FP-2 inhibitors have been designed and synthesized based on three regional optimizations of the lead (R)-2-phenoxycarboxamido-3-(1H-indol-3-yl)-N-benzylpropanamide(1), which was identified using structure-based virtual screening in conjunction with surface plasmon resonance (SPR)-based binding assays. Four compounds – 1, 2b, 2k and 2l –showed moderate FP-2 inhibition activity, with IC50 values of 10.0-39.4 μM, and the inhibitory activityof compound 2k was ~3-fold better than that of the prototype compound 1 and may prove useful for the development of micromolar level FP-2 inhibitors. Preliminary SAR data was obtained, while molecular modeling revealed that introduction of H-bond donor or/and acceptor atoms to the phenyl ring moiety in the C region would be likely to produce some additional H-bond interactions, which should consequently enhance molecular bioactivity.

  恶性疟原虫半胱氨酸蛋白酶恶性疟原虫滋养体-2（FP-2）是一种重要的半胱氨酸蛋白酶，也是红细胞恶性疟原虫滋养体的重要血红蛋白酶。发现新的 FP-2 抑制剂是目前寻找潜在疟疾治疗方法的热门话题。在本研究中，基于对先导物 (R)-2-phenoxycarboxamido-3-(1H-indol-3-yl)-N-benzylpropanamide(1) 的三次区域优化，设计并合成了一系列新型小分子 FP-2 抑制剂。1、2b、2k 和 2l 四种化合物显示出中等程度的 FP-2 抑制活性，IC50 值为 10.0-39.4 μM，其中化合物 2k 的抑制活性比原型化合物 1 的抑制活性高出约 3 倍，可能有助于开发微摩尔水平的 FP-2 抑制剂。研究获得了初步的 SAR 数据，而分子模型显示，在 C 区的苯环分子中引入 H 键供体或/和受体原子可能会产生一些额外的 H 键相互作用，从而提高分子的生物活性。
• Toward Potent Ghrelin Receptor Ligands Based on Trisubstituted 1,2,4-Triazole Structure. 2. Synthesis and Pharmacological in Vitro and in Vivo Evaluations
  作者：Aline Moulin、Luc Demange、Gilbert Bergé、Didier Gagne、Joanne Ryan、Delphine Mousseaux、Annie Heitz、Daniel Perrissoud、Vittorio Locatelli、Antonio Torsello、Jean-Claude Galleyrand、Jean-Alain Fehrentz、Jean Martinez

  DOI：10.1021/jm0704550

  日期：2007.11.1

  A series of ghrelin receptor ligands based on the trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the significance of the aminoisobutyryl (Aib) moiety, a common feature in numerous growth hormone secretagogues described in the literature: Potent agonist and antagonist ligands of the growth hormone secretagogue receptor type la (GHS-R1a) were obtained, i.e., compounds 41 (JMV2894) and 17 (JMV3031). The best compounds were evaluated for their in vivo activity on food intake, after sc injection in rodents. Among the tested compounds, few of them were able to stimulate food intake and some others, i.e., compounds 4 (JMV2959), 17, and 52 (JMV3021), acted as potent in vivo antagonist of hexarelin-stimulated food intake. These compounds did not stimulate growth hormone secretion in rats and furthermore did not antagonize growth hormone secretion induced by hexarelin, revealing that it is possible to modulate food intake without altering growth hormone secretion.
• New Trisubstituted 1,2,4-Triazole Derivatives as Potent Ghrelin Receptor Antagonists. 3. Synthesis and Pharmacological in Vitro and in Vivo Evaluations
  作者：Aline Moulin、Luc Demange、Joanne Ryan、Delphine Mousseaux、Pierre Sanchez、Gilbert Bergé、Didier Gagne、Daniel Perrissoud、Vittorio Locatelli、Antonio Torsello、Jean-Claude Galleyrand、Jean-Alain Fehrentz、Jean Martinez

  DOI：10.1021/jm701292s

  日期：2008.2.1

  Ghrelin receptor ligands based on trisubstituted 1,2,4-triazole structure were synthesized and evaluated for their in vitro binding and biological activity. In this study, we explored the replacement of the alpha-aminoisobutyryl moiety by aromatic or heteroaromatic groups. Compounds 5 and 34 acted as potent in vivo antagonists of hexarelin-stimulated food intake. These two compounds did not stimulate growth hormone secretion in rodents and did not antagonize growth hormone secretion induced by hexarelin.
• Amine Activation:<i>N</i>-Arylamino Acid Amide Synthesis from Isothioureas and Amino Acids
  作者：Yan-Ping Zhu、Pieter Mampuys、Sergey Sergeyev、Steven Ballet、Bert U. W. Maes

  DOI：10.1002/adsc.201700134

  日期：2017.7.17

  functional group compatibility, with respect to side chain functionality of the amino acid (e. g. aliphatic and aromatic OH, (hetero)aromatic NH, amide NH, thioether), and the chiral amino acids do not undergo epimerization. The mechanism of the new amide synthesis has been studied.

  Ñ -arylamino酰胺已经通过基于新方法被合成ñ -芳基胺活化成异硫脲，随后用下铁催化氨基酸反应。可以使用三组分反应与市售试剂叔丁基异氰化物和S-苯基苯硫代磺酸盐轻松地制备活化的N-芳基胺。相对于氨基酸（例如脂族和芳族OH，（杂）芳族NH，酰胺NH，硫醚）的侧链官能度，该方案显示出广泛的官能团相容性，并且手性氨基酸不发生差向异构化。已经研究了新酰胺合成的机理。