4-bromobutyltetra-O-acetyl-β-D-glucopyranoside | 16977-84-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: 4-bromobutyltetra-O-acetyl-β-D-glucopyranoside
• 英文别名: (2R,3R,4S,5R,6R)-2-(acetoxymethyl)-6-(4-bromobutoxy)tetrahydro-2H-pyran-3,4,5-triyl triacetate；Tetraacetyl-(4-brombutyl)-β-D-glucosid；[(2R,3R,4S,5R,6R)-3,4,5-triacetyloxy-6-(4-bromobutoxy)oxan-2-yl]methyl acetate
• CAS: 16977-84-7
• 化学式: C₁₈H₂₇BrO₁₀
• 分子量: 483.31
• InChiKey: FYFIHZHWASQLCK-UYTYNIKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  29
• 可旋转键数：
  14
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  124
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  4-bromobutyltetra-O-acetyl-β-D-glucopyranoside 在 sodium methylate 、 caesium carbonate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0~50.0 ℃ 、101.33 kPa 条件下， 反应 4.5h， 生成 (2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-(4-(4-(7-morpholino-5-(3-phenyl-1H-pyrazol-1-yl)furo[3,2-b]pyridin-2-yl)-1H-pyrazol-1-yl)butoxy)tetrahydro-2H-pyran-3,4,5-triol
  参考文献：
  名称：

  [EN] 7-MORPHOLINO-5-(3-PHENYL-1 H-PYRAZOL-1 -YL)-FURO[3,2-B]PYRIDINE DERIVATIVES AND SIMILAR COMPOUNDS AS PIKFYVE KINASE INHIBITORS FOR THE TREATMENT OF E.G. AMYOTROPHIC LATERAL SCLEROSIS (ALS)
  [FR] DÉRIVÉS DE 7-MORPHOLINO-5-(3-PHÉNYL-1H-PYRAZOL-1-YL)-FURO[3,2-B]PYRIDINE ET COMPOSÉS SIMILAIRES SERVANT D'INHIBITEURS DE LA PIKFYVE KINASE POUR LE TRAITEMENT PAR EXEMPLE, DE LA SCLÉROSE LATÉRALE AMYOTROPHIQUE (ALS)

  摘要：

  The present invention relates to compounds of formula (I) that are inhibitors of PlKfyve kinase and are therefore useful for the treatment of e.g. neurological diseases, such as e.g. amyotrophic lateral sclerosis (ALS), Parkinson's disease, Alzheimer's disease, Huntington's disease, ADHD, schizophrenia, depression, or bipolar disorder. An exemplary compound is e.g. 7-morpholino-5-(3-phenyl-lH- pyrazol-l-yl)-2-(lH-pyrazol-4-yl)furo[3, 2-b]pyridine (compound 10) Data on the PlKfyve kinase inhibition are provided, e.g.:

  公开号：

  WO2022256299A1
• 作为产物：
  描述：

  2,3,4,6-四-O-乙酰-β-D-吡喃葡萄糖 在 三氟甲磺酸三甲基硅酯 、 potassium carbonate 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 3.0h， 生成 4-bromobutyltetra-O-acetyl-β-D-glucopyranoside
  参考文献：
  名称：

  [EN] 7-MORPHOLINO-5-(3-PHENYL-1 H-PYRAZOL-1 -YL)-FURO[3,2-B]PYRIDINE DERIVATIVES AND SIMILAR COMPOUNDS AS PIKFYVE KINASE INHIBITORS FOR THE TREATMENT OF E.G. AMYOTROPHIC LATERAL SCLEROSIS (ALS)
  [FR] DÉRIVÉS DE 7-MORPHOLINO-5-(3-PHÉNYL-1H-PYRAZOL-1-YL)-FURO[3,2-B]PYRIDINE ET COMPOSÉS SIMILAIRES SERVANT D'INHIBITEURS DE LA PIKFYVE KINASE POUR LE TRAITEMENT PAR EXEMPLE, DE LA SCLÉROSE LATÉRALE AMYOTROPHIQUE (ALS)

  摘要：

  The present invention relates to compounds of formula (I) that are inhibitors of PlKfyve kinase and are therefore useful for the treatment of e.g. neurological diseases, such as e.g. amyotrophic lateral sclerosis (ALS), Parkinson's disease, Alzheimer's disease, Huntington's disease, ADHD, schizophrenia, depression, or bipolar disorder. An exemplary compound is e.g. 7-morpholino-5-(3-phenyl-lH- pyrazol-l-yl)-2-(lH-pyrazol-4-yl)furo[3, 2-b]pyridine (compound 10) Data on the PlKfyve kinase inhibition are provided, e.g.:

  公开号：

  WO2022256299A1

文献信息

• Stepwise triple-click functionalization of synthetic peptides
  作者：Anna Kovalová、Radek Pohl、Milan Vrabel

  DOI：10.1039/c8ob01617h

  日期：——

  increasing popularity of peptides as promising molecular scaffolds for biomedical applications and as valuable biochemical probes makes new methods allowing for their modification highly desirable. We describe herein an optimized protocol based on a sequence of CuAAC click reactions and selective deprotection steps, which leads to an efficient multi-functionalization of synthetic peptides. The methodology

  肽作为用于生物医学应用的有前景的分子支架和有价值的生化探针的日益普及，使得对其修饰进行修饰的新方法成为非常需要的。我们在本文中基于CuAAC点击反应和选择性脱保护步骤的序列描述了优化的方案，其导致合成肽的有效多功能化。该方法已成功地用于构建确定的杂糖肽和含荧光猝灭剂的蛋白酶探针。因此，已开发的化学方法代表了对可用工具箱的重要补充，这些工具箱可实现肽的高效合成后修饰。许多叠氮化物探针的商业可用性进一步极大地扩展了所述方法的应用潜力。
• Monosaccharide-Linked Inhibitors of <i>O</i>⁶-Methylguanine-DNA Methyltransferase (MGMT):  Synthesis, Molecular Modeling, and Structure−Activity Relationships
  作者：Jost Reinhard、William E. Hull、Claus-Wilhelm von der Lieth、Uta Eichhorn、Hans-Christian Kliem、Bernd Kaina、Manfred Wiessler

  DOI：10.1021/jm010006e

  日期：2001.11.1

  A series of potential inhibitors of the human DNA repair protein O-6-methylguanine-DNA methyltransferase (MGMT) were synthesized, characterized in detail by NMR, and tested for their ability to deplete MGMT activity in vitro. The new compounds, omega-[O-6-R-guan-9-yl]-(CH2)(n)-beta -d-glucosides with R = benzyl or 4-bromothenyl and omega = n = 2, 4, ... 12, were compared with the established inhibitors O-6 -benzylguanine (O-6-BG), 8-aza-O-6-benzylguanine (8-aza-BG), and O-6-(4-bromothenyl)guanine (4-BTG), which exhibit in an in vitro assay IC50 values of 0.62, 0.038, and 0.009 muM, respectively. Potential advantages of the glucosides are improved water solubility and selective uptake in tumor cells. The 4-BTG glucosides with n = 2, 4, 6 show moderate inhibition with an IC50 of ca. 0.5 muM, while glucosides derived from BG and 8-aza-BG showed significantly poorer inhibition compared to the parent compounds. The 4-BTG glucosides with n = 8, 10, 12 were effective inhibitors with IC50 values of ca. 0.03 muM. To understand this behavior, extensive molecular modeling studies were performed using the published crystal structure of MGMT (PDB entry: 1QNT). The inhibitor molecules were docked into the BG binding pocket, and molecular dynamics simulations with explicit water molecules were carried out. Stabilization energies for the interactions of specific regions of the inhibitor and individual amino acid residues were calculated. The alkyl spacer is located in a cleft along helix 6 of MGMT. With increasing spacer length there is increasing interaction with several amino acid residues which play an important role in the proposed nucleotide flipping mechanism required for DNA repair.