methyl 7,8,9-tri-O-acetyl-2,6-anhydro-5-(tert-butoxycarboxyamido)-4-azido-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enoate | 171241-95-5

• 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: methyl 7,8,9-tri-O-acetyl-2,6-anhydro-5-(tert-butoxycarboxyamido)-4-azido-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enoate
• 英文别名: methyl (2R,3R,4S)-4-azido-3-[(2-methylpropan-2-yl)oxycarbonylamino]-2-[(1S,2R)-1,2,3-triacetyloxypropyl]-3,4-dihydro-2H-pyran-6-carboxylate
• CAS: 171241-95-5
• 化学式: C₂₁H₃₀N₄O₁₁
• 分子量: 514.489
• InChiKey: BXNFYUMOGFFDAP-CZIOMAOESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  36
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  167
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  methyl 7,8,9-tri-O-acetyl-2,6-anhydro-5-(tert-butoxycarboxyamido)-4-azido-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enoate 在 氯化铵 、 溶剂黄146 、 三氟乙酸 、 锌 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 4.5h， 生成 (2R,3R,4S)-3-(benzylamino)-4-(5-bromo-3-cyanoindazol-2-yl)-2-[(1R,2R)-1,2,3-trihydroxypropyl]-3,4-dihydro-2H-pyran-6-carboxylic acid
  参考文献：
  名称：

  [EN] ANTIVIRAL COMPOUNDS AND USES THEREOF
  [FR] COMPOSÉS ANTIVIRAUX ET LEURS UTILISATIONS

  摘要：

  The present disclosure relates to a compound of formula (I), or anN-oxide, pharmaceutically acceptable salt, prodrug or stereoisomer thereof. The present disclosure also relates to pharmaceutical compositions comprising the compound. The present disclosure further relates to methods and uses of the compound in treating or preventing a disease, disorder or condition caused by viral infection in a subject.

  公开号：

  WO2024026536A1
• 作为产物：
  描述：

  5-乙酰氨基-7,8,9-O-三乙酰基-2,6-脱水-4-叠氮-3,4,5-三脱氧-D-甘油-D-半乳-2-壬烯酸甲酯 在 吡啶 、 4-二甲氨基吡啶 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 3.0h， 生成 methyl 7,8,9-tri-O-acetyl-2,6-anhydro-5-(tert-butoxycarboxyamido)-4-azido-3,4,5-trideoxy-D-glycero-D-galacto-non-2-enoate
  参考文献：
  名称：

  人类神经氨酸酶1（NEU1）的选择性抑制剂

  摘要：

  人神经氨酸酶（NEU）的抑制剂被认为是研究NEU生物学功能的重要工具，将是阐明这些酶在调节细胞聚糖组成中的作用的有效工具。在这里，我们报告发现人类神经氨酸酶1（NEU1）和神经氨酸酶2（NEU2）酶具有特殊效力的选择性抑制剂的发现。修饰的2-deoxy-2,3-didehydro- N的文库合成了具有乙酰基神经氨酸（DANA）类似物的C5-或C9位置，并针对四种人类神经氨酸酶同工酶（NEU1-4）进行了评估。NEU1可以很好地容纳在C5和C9位置带有酰胺连接基的疏水基团，并且发现一个六氨基基团在两个位置均具有最佳效价。尽管C5-六氨基-C9-六氨基-DANA类似物未显示出协同修饰的协同改进，但在单个位置上延伸的烷基酰胺与第二个位置上的较小基团相结合，增强了效力。确定的最佳NEU1抑制剂是具有K i与其他同工酶相比，具有53±5 nM的选择性和340倍的选择性。此外，我们证明了C5修饰结合C

  DOI：

  10.1021/acs.jmedchem.8b01411

文献信息

• [EN] METHODS OF PREVENTING OR TREATING ATHEROSCLEROSIS WITH INHIBITORS OF SPECIFIC ISOENZYMES OF HUMAN NEURAMINIDASE<br/>[FR] MÉTHODES DE PRÉVENTION OU DE TRAITEMENT DE L'ATHÉROSCLÉROSE AVEC DES INHIBITEURS D'ISOENZYMES SPÉCIFIQUES DE LA NEURAMINIDASE HUMAINE
  申请人：UNIV ALBERTA

  公开号：WO2018213933A1

  公开（公告）日：2018-11-29

  The present invention provides a method of preventing or treating atherosclerosis or a symptom thereof comprising administering to a subject in need thereof a specific inhibitor of neuraminidase 1 (neu1); neuraminidase 3 (neu3); or a bispecific inhibitor of neu1 or neu3 of formula I; (I) and a compound of formula I.

  本发明提供了一种预防或治疗动脉粥样硬化或其症状的方法，包括向需要的受试者施用神经氨酸酶1（neu1）的特异性抑制剂；神经氨酸酶3（neu3）；或式I的neu1或neu3的双特异性抑制剂；（I）和式I的化合物。
• [EN] DERIVATIVES OF 2-DEOXY-2,3-DEHYDRO-N-ACETYLNEURAMINIC ACID (DANA)<br/>[FR] DERIVES DE L'ACIDE 2-DESOXY-2,3-DESHYDRO-N-ACETYLNEURAMINIQUE (DANA)
  申请人：BIOTA SCIENTIFIC MANAGEMENT PTY LTD

  公开号：WO1995018800A1

  公开（公告）日：1995-07-13

  (EN) (4S, 5R, 6R)-4-Guanidino-5-methanesulphonylamino-6-[(1S,2R)-1,2,3-trihydroxypropyl-5,6-dihydro-4H-pyran-3-carboxylic acid and its physiologically acceptable derivatives and solvates are inhibitors of viral neuraminidase.(FR) L'acide (4S, 5R, 6R)-4-guanidino-5-méthanesulfonylamino-6-[(1S, 2R)-1,2,3-trihydroxypropyl-5,6-dihydro-4H-pyranne-3-carboxylique, ses dérivés ainsi que ses solvates physiologiquement tolérables sont des inhibiteurs de la neuraminidase virale.

  (4S,5R,6R)鸟苷二胺-5-甲基砜氨基-6-[(1S,2R)-1,2,3-三羟基丙基-5,6-双氢-4H-pyran-3-酸]及其生理可接受的衍生物和可溶化衍生物是抑制病毒神经元酶的化合物。
• Exploring Human Parainfluenza Virus Type-1 Hemagglutinin–Neuraminidase as a Target for Inhibitor Discovery
  作者：Ibrahim M. El-Deeb、Patrice Guillon、Moritz Winger、Tanguy Eveno、Thomas Haselhorst、Jeffrey C. Dyason、Mark von Itzstein

  DOI：10.1021/jm500759v

  日期：2014.9.25

  Human parainfluenza virus type 1 is the major cause of croup in infants and young children. There is currently neither vaccine nor clinically effective treatment for parainfluenza virus infection. Hemagglutinin-neuraminidase glycoprotein is a key protein in viral infection, and its inhibition has been a target for 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (Neu5Ac2en)-based inhibitor development. In this study, we explore the effect of C-5 modifications on the potency of Neu5Ac2en derivatives that target the human parainfluenza type-1 hemagglutinin-neuraminidase protein. Our study demonstrates that the replacement of the Neu5Ac2en C-5 acetamido moiety with more hydrophobic alkane-based moieties improves the inhibitory potency for both hemagglutinin-neuraminidase functions. These findings shed light on the importance of C-S substitution on Neu5Ac2en in the design of novel sialic acid-based inhibitors that target human parainfluenza type-1 hemagglutinin-neuraminidase.
• Synthesis and influenza virus sialidase inhibitory activity of analogues of 4-guanidino-Neu5Ac2en (GG167) with modified 5-substituents
  作者：PW Smith、ID Starkey、PD Howes、SL Sollis、SP Keeling、PC Cherry、M von Itzstein、WY Wu、B Jin

  DOI：10.1016/0223-5234(96)80447-8

  日期：1996.1

  Analogues of 4-guanidino-Neu5Ac2en (GG167) have been prepared containing alternative amide and sulfonamide substituents at the 5-position. (4S,5R,6R)-4-guanidino-5-(2,2,2-trifluoroacetylamino)-6-(1R,2R,3-trihydroxypropyl)-5,6-dihydro-4H-pyran-2-carboxylic acid 5 and (4S,5R,6R)-4-guanidino-5-methanesulfonylamino-6-(1R,2R,3-trihydroxypropyl)-5,6-dihydro-4H-pyran-2-carboxylic acid 6 were the only analogues which approached the activity of GG167, showing potent inhibition of influenza virus sialidases and good antiviral activity in vitro.