5-acetamido-2,6-anhydro-9-azido-3,5,9-trideoxy-D-glycero-D-galacto-non-2-enonic acid | 138250-79-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 5-acetamido-2,6-anhydro-9-azido-3,5,9-trideoxy-D-glycero-D-galacto-non-2-enonic acid
• 英文别名: (2R,3R,4S)-3-acetamido-2-((1R,2R)-3-azido-1,2-dihydroxypropyl)-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylate；(2R,3R,4S)-3-acetamido-2-[(1R,2R)-3-azido-1,2-dihydroxypropyl]-4-hydroxy-3,4-dihydro-2H-pyran-6-carboxylic acid
• CAS: 138250-79-0
• 化学式: C₁₁H₁₆N₄O₇
• 分子量: 316.271
• InChiKey: ALVXTNDDVFJVAI-UFGQHTETSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.9
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  151
• 氢给体数：
  5
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  5-acetamido-2,6-anhydro-9-azido-3,5,9-trideoxy-D-glycero-D-galacto-non-2-enonic acid 在 吡啶 、 1,3-丙二硫醇 、 三乙胺 、 sodium hydroxide 作用下， 以 水 为溶剂， 反应 24.0h， 以95%的产率得到5-acetamido-9-amino-2,6-anhydro-3,5,9-trideoxy-D-glycero-D-galacto-non-2-enonic acid
  参考文献：
  名称：

  [EN] SIALIDASE INHIBITORS AND PREPARATION THEREOF
  [FR] INHIBITEURS DE SIALIDASE ET LEUR PRÉPARATION

  摘要：

  公开号：

  WO2018201058A3
• 作为产物：
  描述：

  methyl-2,3-didehydro-4,7,8,9-tetra-O-acetyl-N-acetylneuraminate 在 吡啶 、 sodium hydroxide 、 sodium azide 、 sodium methylate 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 14.0h， 生成 5-acetamido-2,6-anhydro-9-azido-3,5,9-trideoxy-D-glycero-D-galacto-non-2-enonic acid
  参考文献：
  名称：

  Synthesis of a Neu2en5Ac analog hapten and isolation of monoclonal antibody to Neu2en5Ac

  摘要：

  Neu2en5Ac is a minor component of body fluids and is abundant in sialuria, but no antibody to detect it has been reported. 5-Acetamido-2,6-anhydro-9-glutaramido-3,5,9-trideoxy-D-glycero-D-galacto-non-2-enonic acid has been synthesized and conjugated with keyhole limpet hemocyanin (KLH) for immunization. A hybridoma named SIC172 was obtained that produces a monoclonal antibody (MAb) to Neu2en5Ac. SIC172 MAb in culture supernatant bound strongly to the hapten conjugated to BSA in ELISA, but slightly to fetuin, a glycoprotein which is rich in Neu5Ac. SIC172 MAb (IgG3(kappa)), purified with a protein A/G affinity column, bound strongly to fetuin. Neu2en5Ac competed with the MAb in binding in amounts as low as 3 mu M, while the competition of Neu5Ac appeared at amounts of more than 300 mu M. SIC172 MAb is a unique MAb specific to Neu2en5Ac and might be useful for detecting Neu2en5Ac, which occurs naturally and in sialuria. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0008-6215(99)00023-3

文献信息

• Triazole-linked transition state analogs as selective inhibitors against V. cholerae sialidase
  作者：Teri J. Slack、Wanqing Li、Dashuang Shi、John B. McArthur、Gengxiang Zhao、Yanhong Li、An Xiao、Zahra Khedri、Hai Yu、Yang Liu、Xi Chen

  DOI：10.1016/j.bmc.2018.10.028

  日期：2018.11

  3-didehydro-N-acetylneuraminic acid (Neu5Ac2en or DANA) were designed and synthesized as triazole-linked transition state analogs. Inhibition studies revealed that glycopeptide analog E-(TriazoleNeu5Ac2en)-AKE and compound (TriazoleNeu5Ac2en)-A were selective inhibitors against Vibrio cholerae sialidase, while glycopeptide analog (TriazoleNeu5Ac2en)-AdE selectively inhibited Vibrio cholerae and A. ureafaciens sialidases

  唾液酸酶或神经氨酸酶是催化末端唾液酸从寡糖和糖缀合物裂解的酶。它们在细菌和病毒感染中发挥重要作用，并且一直是药物开发的有吸引力的目标。基于结构的药物设计已经产生了针对甲型流感病毒神经氨酸酶的有效抑制剂，这些病毒已成功用作批准的治疗剂。然而，仍在积极寻找针对细菌和人类唾液酸酶的选择性和有效抑制剂。在晶体结构分析的指导下，2-deoxy-2,3-didehydro- N的几种衍生物-乙酰神经氨酸（Neu5Ac2en 或 DANA）被设计并合成为三唑连接的过渡态类似物。抑制研究表明，糖肽类似物 E-(TriazoleNeu5Ac2en)-AKE 和化合物 (TriazoleNeu5Ac2en)-A 是霍乱弧菌唾液酸酶的选择性抑制剂，而糖肽类似物 (TriazoleNeu5Ac2en)-AdE 选择性抑制霍乱弧菌和A. ureafaciens唾液酸酶。
• A Strategy for Neuraminidase Inhibitors Using Mechanism-Based Labeling Information
  作者：Hiroshi Hinou、Risho Miyoshi、Yasuaki Takasu、Hirokazu Kai、Masaki Kurogochi、Shingo Arioka、Xiao-Dong Gao、Nobuaki Miura、Naoki Fujitani、Shinya Omoto、Tomokazu Yoshinaga、Tamio Fujiwara、Takeshi Noshi、Hiroko Togame、Hiroshi Takemoto、Shin-Ichiro Nishimura

  DOI：10.1002/asia.201000594

  日期：2011.4.4

  A potent inhibitor for Vibrio cholerae neuraminidase (VCNA) was developed by using a novel two‐step strategy, a target amino acid validation using mechanism‐based labeling information, and a potent inhibitor search using a focused library. The labeling information suggested the hidden dynamics of a loop structure of VCNA, which can be a potential target of the novel inhibitor. A focused library composed

  一种有效的霍乱弧菌神经氨酸酶（VCNA）抑制剂是通过采用新型的两步策略，使用基于机理的标记信息进行靶氨基酸验证以及使用聚焦库进行的有效抑制剂搜索而开发的。标记信息暗示了VCNA环状结构的隐藏动力学，该结构可能是新型抑制剂的潜在靶标。用2,3-脱氢-N-乙酰神经氨酸的9-叠氮化物衍生物（DANA）制备了由187种化合物组成的聚焦文库，以中断标记残基环的功能。抑制剂3c显示出有效的抑制特性，并且是FANA（一种NDANA的三氟乙酰基衍生物。用去污剂和Lineweaver-Burk图对抑制剂进行的验证研究表明，9位取代基会与目标环部分发生疏水性相互作用，从而在DANA骨架上增加了非竞争性的抑制特性。该信息使我们能够设计具有3c和FANA组合结构的化合物4。在测试的病毒，细菌和哺乳动物神经氨酸酶中​​，化合物4显示出对VCNA的最强抑制作用（K i = 73 n M，混合抑制）。
• SIALIDASE AND RECOMBINANT CELL LINES
  申请人：——

  公开号：US20020076791A1

  公开（公告）日：2002-06-20

  A recombinant cell line has a constitutive sialidase whose functional expression is disrupted, for example by homologous recombination or using antisense RNA. Sialidase is purified from cell culture fluid of Chinese hamster ovary cells. Nucleic acid encoding sialidase is obtained using an oligonucleotide probe designed using amino acid sequence data on the sialidase.

  重组细胞系具有组成型硅糖苷酶，其功能表达被破坏，例如通过同源重组或使用反义 RNA。从中国仓鼠卵巢细胞的细胞培养液中纯化出硅糖苷酶。使用根据硅糖苷酶的氨基酸序列数据设计的寡核苷酸探针获得编码硅糖苷酶的核酸。
• Sialidase and recombinant cell lines
  申请人：Genentech, Inc.

  公开号：US20030148493A1

  公开（公告）日：2003-08-07

  A recombinant cell line has a constitutive sialidase whose functional expression is disrupted, for example by homologous recombination or using antisense RNA. Sialidase is purified from cell culture fluid of Chinese hamster ovary cells. Nucleic acid encoding sialidase is obtained using an oligonucleotide probe designed using amino acid sequence data on the sialidase.

  重组细胞系具有组成型硅糖苷酶，其功能表达被破坏，例如通过同源重组或使用反义 RNA。从中国仓鼠卵巢细胞的细胞培养液中纯化出硅糖苷酶。使用根据硅糖苷酶的氨基酸序列数据设计的寡核苷酸探针获得编码硅糖苷酶的核酸。
• Inhibition of human neuraminidase 3 (NEU3) by C9-triazole derivatives of 2,3-didehydro-N-acetyl-neuraminic acid
  作者：Yao Zou、Amgad Albohy、Mahendra Sandbhor、Christopher W. Cairo

  DOI：10.1016/j.bmcl.2010.09.111

  日期：2010.12

  We report the synthesis of a series of C9 and N5Ac modified analogs of 2,3-didehydro-N-acetyl-neuraminic acid (DANA) and their inhibitory potency for the human neuraminidase 3 (NEU3) enzyme. We were able to generate a small library of compounds through the synthesis of azide derivatives of DANA, followed by Cu-catalyzed azide-alkyne cycloaddition (CuAAC) to generate triazole-containing inhibitors. Our results suggest that NEU3 can tolerate large hydrophobic groups at the C9 position; however, none of the derivatives made at the N5Ac side-chain were active. We identify three new inhibitors that have comparable potency to the best reported inhibitors of the enzyme. (C) 2010 Elsevier Ltd. All rights reserved.