L-tryptophan methylamide | 53708-63-7

• 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: L-tryptophan methylamide
• 英文别名: (S)-2-amino-3-(1H-indol-3-yl)-N-methylpropanamide；(2S)-2-amino-3-(1H-indol-3-yl)-N-methylpropanamide
• CAS: 53708-63-7
• 化学式: C₁₂H₁₅N₃O
• mdl: MFCD14590225
• 分子量: 217.271
• InChiKey: YCTBLMQFTMPXBD-JTQLQIEISA-N

物化性质

• 熔点：
  123-125 °C
• 沸点：
  513.4±45.0 °C(Predicted)
• 密度：
  1.222±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 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：

  L-tryptophan methylamide 在 palladium on activated charcoal 氢气 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 伊洛马司他
  参考文献：
  名称：

  Inhibition of Membrane-Type 1 Matrix Metalloproteinase by Hydroxamate Inhibitors:  An Examination of the Subsite Pocket

  摘要：

  The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been reported to mediate the activation of pro-gelatinase A (proMMP-2), which is associated with tumor proliferation and metastasis. MT1-MMP can also digest extracellular matrix (ECM) such as interstitial collagens, gelatin, and proteoglycan and thus may play an important role in pathophysiological digestion of ECM. We studied the inhibitory effect of various hydroxamate MMP inhibitors, including known inhibitors such as BB-94, BB-2516, GM6001, and Ro31-9790, on a deletion mutant of MT1-MMP lacking the transmembrane domain (Delta MT1) to further characterize the enzyme and develop a selective inhibitor for MT1-MMP. The evaluation of the inhibitory activities of various hydroxamates reveals general structural profiles affecting selectivities toward MMPs. In particular, a longer side chain at the P1' position is preferable for the binding to MMP-2, -3, and -9 and MT1-MMP. For the P2' position, an a-branched alkyl group is critical for the binding toward Delta MT1, while the introduction of a bulky group at the a-position of hydroxamic acid seems to diminish the activity against Delta MT1. Summation of the data on the sensitivity of Delta MT1 to various hydroxamate inhibitors indicates that (1) the volume of the S1' subsite of Delta MT1 is similar to that of MMP-2, -3, and -9, which is bigger than that of MMP-1, and (2) the S1 and S2' subsites are narrower than those in other MMPs. On the basis of these results, the hydroxamates with a P1' phenylpropyl and P2' alpha-branched alkyl group were synthesized and evaluated for inhibitory activity. These inhibitors (1h,i) showed strong activity against Delta MT1 over MMP-1, but no selectivity between Delta MT1 and MMP-9. These results are explained using molecular modeling studies conducted on MT1-MMP.

  DOI：

  10.1021/jm970404a
• 作为产物：
  描述：

  L-色氨酸乙酯盐酸盐 在 甲胺 、 碳酸氢钠 作用下， 以 乙醇 、 水 为溶剂， 反应 120.0h， 以6.1 g的产率得到L-tryptophan methylamide
  参考文献：
  名称：

  Preparation of the MacMillan imidazolidinones

  摘要：

  A general method for the preparation of the MacMillan imidazolidinones is described. Treatment of an alpha-amino amide with a carbonyl compound in refluxing chloroform in the presence of Yb(OTf)(3) (1 mol %) provides convenient access to the corresponding imidazolidinones. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.04.009

文献信息

• SUBSTITUTED CYCLOHEXYLDIAMINES
  申请人：Zemolka Saskia

  公开号：US20090247591A1

  公开（公告）日：2009-10-01

  The invention relates to compounds that have an affinity to the μ-opioid receptor and the ORL 1-receptor, methods for their production, medications containing these compounds and the use of these compounds for the treatment of pain or other conditions.

  这项发明涉及具有亲和力与μ-阿片受体和ORL 1-受体的化合物，其生产方法，含有这些化合物的药物以及利用这些化合物治疗疼痛或其他疾病的用途。
• Synthesis of novel modified dipeptide inhibitors of human collagenase: .beta.-mercapto carboxylic acid derivatives
  作者：Belle Beszant、John Bird、Laramie M. Gaster、Gregory P. Harper、Ian Hughes、Eric H. Karran、Roger E. Markwell、Anette J. Miles-Williams、Stephen A. Smith

  DOI：10.1021/jm00077a006

  日期：1993.12

  diastereoisomer was 56d (IC50 12 nM) with the R,R,S configuration. It appeared that the orientation of the P1' and the thiol-bearing centers to each other is a more critical influence on potency than any absolute stereochemical requirements. It is suggested that the high potency of the beta-mercapto carboxylic acid derivatives may be a consequence of bidentate coordination of the thiol and carbonyl

  描述了一系列人胶原酶的含巯基的修饰二肽抑制剂（8）的合成，这些抑制剂在推定的P1位（巯基的β位）掺入了多种羧酸衍生物。在体外评估了这些化合物通过纯化的人肺成纤维细胞胶原酶抑制大鼠皮肤1型胶原降解的能力，并描述了结构-活性关系研究。通过在P1位置掺入甲基（化合物43a，56a和57ab）或苄基酯（44a），可获得最佳效价（纳摩尔范围内的IC50值）。也可以容纳小的酰胺（例如伯酰胺47a），但通常，增加P1酰胺取代基的大小会降低效能。发现PheNHMe，TrpNHMe和Tyr（Me）NHMe取代基是大约等价的P2'残基。用P2'位置的（S）-TrpNHMe测试该化合物的所有四个非对映异构体56a-d的结果表明，S，S，S非对映异构体56a具有最高效价（IC50 2.5 nM），第二强的非对映异构体是具有R，R，S配置的56d（IC50 12 nM）。似乎P1'和带有硫醇的中心彼此之间的方向比任
• Copper-Catalyzed Diastereoselective Arylation of Tryptophan Derivatives: Total Synthesis of (+)-Naseseazines A and B
  作者：Madeleine E. Kieffer、Kangway V. Chuang、Sarah E. Reisman

  DOI：10.1021/ja4023557

  日期：2013.4.17

  A copper-catalyzed arylation of tryptophan derivatives is reported. The reaction proceeds with high site- and diastereoselectivity to provide aryl pyrroloindoline products in one step from simple starting materials. The utility of this transformation is highlighted in the five-step syntheses of the natural products (+)-naseseazine A and B.

  报道了色氨酸衍生物的铜催化芳基化。该反应以高位点和非对映选择性进行，从简单的起始材料一步即可提供芳基吡咯并二氢吲哚产物。这种转化的效用在天然产物 (+)-naseseazine A 和 B 的五步合成中得到了强调。
• FKBP BINDING COMPOSITION AND PHARMACEUTICAL USE THEREOF
  申请人：KOSLEY Raymond W.

  公开号：US20080139556A1

  公开（公告）日：2008-06-12

  A composition for binding FKBP proteins is disclosed, along with a method of treating conditions associated with neuronal degeneration, wherein said composition comprises a compound of formula I, wherein, R, R 1 , R 2 , R 3 and X are as defined herein.

  揭示了一种用于结合FKBP蛋白的组合物，以及一种治疗与神经退行性疾病相关的条件的方法，其中所述组合物包括式I的化合物， 其中，R、R1、R2、R3和X如本文所定义。
• Small-Molecule Inhibitors That Target Protein-Protein Interactions in the RAD51 Family of Recombinases
  作者：Duncan E. Scott、Anthony G. Coyne、Ashok Venkitaraman、Tom L. Blundell、Chris Abell、Marko Hyvönen

  DOI：10.1002/cmdc.201402428

  日期：2015.2

  The development of small molecules that inhibit protein–protein interactions continues to be a challenge in chemical biology and drug discovery. Herein we report the development of indole‐based fragments that bind in a shallow surface pocket of a humanised surrogate of RAD51. RAD51 is an ATP‐dependent recombinase that plays a key role in the repair of double‐strand DNA breaks. It both self‐associates

  抑制蛋白质与蛋白质相互作用的小分子的发展仍然是化学生物学和药物发现中的挑战。在这里，我们报道了结合吲哚基片段的发展，该片段结合在RAD51人性化替代物的浅表囊中。RAD51是一种依赖于ATP的重组酶，在双链DNA断裂的修复中起关键作用。它既可以自缔合，与DNA形成细丝结构，又可以通过常见的“ FxxA”四肽基序与BRCA2蛋白相互作用。我们精心设计了先前确定的靶向FxxA序列位点的片段，并开发了比初始片段强约500倍的小分子抑制剂。铅化合物与BRCA2衍生的Ac-FHTA-NH 2竞争肽和RAD51的自缔合肽，但它们对ATP结合没有影响。这项研究是首次报道针对这一具有挑战性的目标的小分子量片段的研究。