methyl 2-azido-3-O-benzoyl-6-O-tert-butyldiphenylsilyl-2-deoxy-1-thio-β-D-glucopyranoside | 659722-21-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2-azido-3-O-benzoyl-6-O-tert-butyldiphenylsilyl-2-deoxy-1-thio-β-D-glucopyranoside
• 英文别名: [(2R,3S,4R,5R,6S)-5-azido-2-[[tert-butyl(diphenyl)silyl]oxymethyl]-3-hydroxy-6-methylsulfanyloxan-4-yl] benzoate
• CAS: 659722-21-1
• 化学式: C₃₀H₃₅N₃O₅SSi
• 分子量: 577.777
• InChiKey: FWQQXUPVLIQEMA-ROJUMVHJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.92
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 2-azido-3-O-benzoyl-6-O-tert-butyldiphenylsilyl-2-deoxy-1-thio-β-D-glucopyranoside 在 三氟化硼乙醚 、 DMTST 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  Method of drug design

  摘要：

  该发明提供了一种识别生物活性化合物的方法，包括：(a)设计第一类化合物库，该库的化合物具有公式(1)的分子多样性扫描，其中库中的每个化合物至少具有下面定义的两个药效团R1至R5，并且库中的化合物具有相同数量的药效团；(b)在一个或多个生物测定中对第一类化合物库进行测定；以及(c)设计第二类化合物库，其中第二类库中的每个化合物相对于第一类库包含一个或多个额外的药效团；使得第一类和第二类库的每个组分均为公式(1)的化合物。

  公开号：

  US09709571B2
• 作为产物：
  描述：

  在 甲醇 、 4-二甲氨基吡啶 、 对甲苯磺酸 作用下， 以 1,2-二氯乙烷 、 乙腈 为溶剂， 生成 methyl 2-azido-3-O-benzoyl-6-O-tert-butyldiphenylsilyl-2-deoxy-1-thio-β-D-glucopyranoside
  参考文献：
  名称：

  Method of drug design

  摘要：

  该发明提供了一种识别生物活性化合物的方法，包括：(a)设计第一类化合物库，该库的化合物具有公式(1)的分子多样性扫描，其中库中的每个化合物至少具有下面定义的两个药效团R1至R5，并且库中的化合物具有相同数量的药效团；(b)在一个或多个生物测定中对第一类化合物库进行测定；以及(c)设计第二类化合物库，其中第二类库中的每个化合物相对于第一类库包含一个或多个额外的药效团；使得第一类和第二类库的每个组分均为公式(1)的化合物。

  公开号：

  US09709571B2

文献信息

• Fighting Obesity with a Sugar-Based Library: Discovery of Novel MCH-1R Antagonists by a New Computational–VAST Approach for Exploration of GPCR Binding Sites
  作者：Alexander Heifetz、Oliver Barker、Geraldine Verquin、Norbert Wimmer、Wim Meutermans、Sandeep Pal、Richard J. Law、Mark Whittaker

  DOI：10.1021/ci4000882

  日期：2013.5.24

  Obesity is an increasingly common disease. While antagonism of the melanin-concentrating hormone-1 receptor (MCH-1R) has been widely reported as a promising therapeutic avenue for obesity treatment, no MCH-1R antagonists have reached the market. Discovery and optimization of new chemical matter targeting MCH-1R is hindered by reduced HTS success rates and a lack of structural information about the

  肥胖是一种越来越常见的疾病。虽然已经广泛报道了黑色素浓缩激素-1受体（MCH-1R）的拮抗作用是肥胖治疗的一种有希望的治疗途径，但尚未有MCH-1R拮抗剂进入市场。降低HTS成功率和缺乏有关MCH-1R结合位点的结构信息，阻碍了针对MCH-1R的新化学物质的发现和优化。X射线晶体学和NMR是结构信息的主要实验来源，它们是膜蛋白的非常缓慢的过程，目前不适用于每种GPCR或GPCR-配体复合物。这种情况极大地限制了这些方法“实时”影响GPCR靶标的药物发现过程的能力，因此，迫切需要其他实用且具有成本效益的替代方法。我们在这里提出一种在概念上具有先驱性的方法，该方法将GPCR建模与VAST技术（稳定模板上的多功能组装）的多种糖基化合物的设计，合成和筛选相集成，以提供有关MCH-1R结合位点的结构见解。这种方法为针对GPCR靶标的基于结构的药物发现（SBDD）创建了一种经济高效的新途径。在我们的工
• Orthogonally Protected Monosaccharide Building Blocks for Solid Phase Production of Diversity Oriented Libraries
  作者：Premraj Rajaratnam、Praveer Gupta、Peter Katavic、Krystle Kuipers、Ngoc Huyh、Sarah Ryan、Tania Falzun、Gerrald B. Tometzki、Laurent Bornaghi、Giang Le Thanh、Giovanni Abbenante、Ligong Liu、Wim Meutermans、Norbert Wimmer、Michael L. West

  DOI：10.1071/ch09480

  日期：——

  The large scale synthesis of three orthogonally protected monosaccharide scaffolds suitable for use in the solid phase preparation of large diversity libraries is presented. Scaffolds based on 2-amino-2-deoxy-d-glucopyranose, 2-amino-2-deoxy-d-allopyranose, and 2,4-diamino-2,4-dideoxy-d-galactopyranose were prepared in good yield and with minimal chromatographic purification from commercially available methyl 2-azido-2-deoxy-1-thio-β-d-glucopyranose and methyl 2-amino-2-deoxy-1-thio-β-d-glucopyranose.

  本文介绍了适合用于固相制备大型多样性文库的三种正交保护单糖支架的大规模合成。基于 2-氨基-2-脱氧-d-吡喃葡萄糖、2-氨基-2-脱氧-d-吡喃全糖和 2,4-二氨基-2,4-二脱氧-d-吡喃半乳糖的支架以良好的收率和最低的色谱纯化率从市售的甲基 2-叠氮-2-脱氧-1-硫代-β-d-吡喃葡萄糖和甲基 2-氨基-2-脱氧-1-硫代-β-d-吡喃葡萄糖制备出来。
• [EN] DERIVATIVES OF MONOSACCHARIDES FOR DRUG DISCOVERY<br/>[FR] DERIVES DE MONOSACCHARIDES UTILISES POUR LA DECOUVERTE DE MEDICAMENTS
  申请人：ALCHEMIA PTY LTD

  公开号：WO2004014929A1

  公开（公告）日：2004-02-19

  New compounds and methods for the preparation of combinatorial libraries of potentially biologically active compounds are based on monosaccharides of formula (I) being a derivative of a furanose or pyranose form of a monosaccharide.

  新型化合物及制备组合化合物库的方法，该化合物库包含可能具有生物活性的化合物，其基础是通式(I)的单糖衍生物，该衍生物为呋喃糖或吡喃糖形式的单糖。
• A Versatile Synthetic Approach toward Diversity Libraries using Monosaccharide Scaffolds
  作者：Giang Le Thanh、Giovanni Abbenante、George Adamson、Bernd Becker、Chris Clark、Glenn Condie、Tania Falzun、Matthias Grathwohl、Praveer Gupta、Michael Hanson、Ngoc Huynh、Peter Katavic、Krystle Kuipers、Ann Lam、Ligong Liu、Maretta Mann、Jeff Mason、Declan McKeveney、Craig Muldoon、Andrew Pearson、Premraj Rajaratnam、Sarah Ryan、Gerry Tometzki、Geraldine Verquin、Jennifer Waanders、Michael West、Neil Wilcox、Norbert Wimmer、Annika Yau、Johannes Zuegg、Wim Meutermans

  DOI：10.1021/jo9021919

  日期：2010.1.1

  The pyranose scaffold is unique in its ability to position pharmacophore substituents in various ways in 3D space, and unique pharmacophore scanning libraries could be envisaged that focus on scanning topography rather than diversity in the type Of substituents. Approaches have been described that make use of amine and acid functionalities on the pyranose scaffolds to append substituents, and this has enabled the generation of libraries of significant structural diversity. Our general aim was to generate libraries of pyranose-based drug-like mimetics, where the substituents are held close to the scaffold, in order to obtain molecules with better defined positions for the pharmacophore substituents. Here we describe the development of a versatile synthetic route toward peptide mimetics build oil 2-amino pyranose scaffolds. The method allows introduction of a wide range of substituent types, it is regio- and stereospecific, and the later diversity steps are performed on solid phase. Further, the same process was applied oil glucose mid allose scaffolds, in the exemplified cases, and is likely adaptable to other pyranose building blocks. The methods developed in this work give access to molecules that position the three selected binding elements in various 3D orientations oil a pyranose scaffold and have been applied for the production of a systematically diverse library of several hundred monosaccharide-based mimetics.
• Biological Diversity from a Structurally Diverse Library: Systematically Scanning Conformational Space Using a Pyranose Scaffold
  作者：Giovanni Abbenante、Bernd Becker、Sébastien Blanc、Chris Clark、Glenn Condie、Graeme Fraser、Matthias Grathwohl、Judy Halliday、Senka Henderson、Ann Lam、Ligong Liu、Maretta Mann、Craig Muldoon、Andrew Pearson、Rajaratnam Premraj、Tracie Ramsdale、Tony Rossetti、Karl Schafer、Giang Le Thanh、Gerald Tometzki、Frank Vari、Géraldine Verquin、Jennifer Waanders、Michael West、Norbert Wimmer、Annika Yau、Johannes Zuegg、Wim Meutermans

  DOI：10.1021/jm1002777

  日期：2010.8.12

  Success in discovering bioactive peptide mimetics is often limited by the difficulties in correctly transposing known binding elements of the active peptide onto a small and metabolically more stable scaffold while maintaining bioactivity. Here we describe a scanning approach using a library of pyranose-based peptidomimetics that is structurally diverse in a systematic manner, designed to cover all possible conformations of tripeptide motifs containing two aromatic groups and one positive charge. Structural diversity was achieved by efficient selection of various chemoforms, characterized by a choice of pyranose scaffold of defined chirality and substitution pattern. A systematic scanning library of 490 compounds was thus designed, produced, and screened in vitro for activity at the somatostatin (sst(1-5)) and melanin-concentrating hormone (MCH1) receptors. Bioactive compounds were found for each target, with specific chemoform preferences identified in each case, which can be used to guide follow-on drug discovery projects without the need for scaffold hopping.