| 1397938-42-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• CAS: 1397938-42-9
• 化学式: C₁₆H₁₁NO₅S
• 分子量: 329.333
• InChiKey: BOJWFCRPJDTEMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.53
• 重原子数：
  23.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  72.91
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  、 在 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 2-azidoethyl (5-acetamido-9-(4H-thieno[3,2-c]chromene-2-carboxamido)-3,5,9-trideoxy-D-glycero-α-D-galacto-2-nonulopyranosylonic acid)-(2→3)-β-D-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-β-D-glucopyranoside
  参考文献：
  名称：

  In Silico-Aided Design of a Glycan Ligand of Sialoadhesin for in Vivo Targeting of Macrophages

  摘要：

  Cell-specific delivery of therapeutic agents using ligand targeting is gaining interest because of its potential for increased efficacy and reduced side effects. The challenge is to develop a suitable ligand for a cell-surface receptor that is selectively expressed on the desired cell. Sialoadhesin (Sn, Siglec-1, CD169), a sialic acid-binding immunoglobulin-like lectin (Siglec) expressed on subsets of resident and inflammatory macrophages, is an attractive target for the development of a ligand-targeted delivery system. Here we report the development of a high-affinity and selective ligancl for Sn that is an analogue of the natural ligand and is capable of targeting liposomal nanoparticles to Sn-expressing cells in vivo. An efficient in silico screen of a library of similar to 8400 carboxylic acids was the key to identifying novel 9-N-acyl-substituted N-acetylneuramic acid (Neu5Ac) substituents as potential lead compounds. A small panel of targets were selected from the screen and synthesized to evaluate their affinities and selectivities. The most potent of these Sn ligands, (4H-thieno[3,2-c]chromene-2-carbamoyl)-Neu5Ac alpha 2-3Gal beta 1-4GlcNAc ((TCC)Neu5Ac), was conjugated to lipids for display on a liposomal nanoparticle for evaluation of targeted delivery to cells. The (TCC)Neu5Ac liposomes were found to target liposomes selectively to cells expressing either murine or human Sn in vitro, and when administered to mice, they exhibited in vivo targeting to Sn-positive macrophages.

  DOI：

  10.1021/ja307501e
• 作为产物：
  描述：

  N-羟基丁二酰亚胺 、 4H-噻吩并[3,2-c]苯并吡喃-2-羧酸 在 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  In Silico-Aided Design of a Glycan Ligand of Sialoadhesin for in Vivo Targeting of Macrophages

  摘要：

  Cell-specific delivery of therapeutic agents using ligand targeting is gaining interest because of its potential for increased efficacy and reduced side effects. The challenge is to develop a suitable ligand for a cell-surface receptor that is selectively expressed on the desired cell. Sialoadhesin (Sn, Siglec-1, CD169), a sialic acid-binding immunoglobulin-like lectin (Siglec) expressed on subsets of resident and inflammatory macrophages, is an attractive target for the development of a ligand-targeted delivery system. Here we report the development of a high-affinity and selective ligancl for Sn that is an analogue of the natural ligand and is capable of targeting liposomal nanoparticles to Sn-expressing cells in vivo. An efficient in silico screen of a library of similar to 8400 carboxylic acids was the key to identifying novel 9-N-acyl-substituted N-acetylneuramic acid (Neu5Ac) substituents as potential lead compounds. A small panel of targets were selected from the screen and synthesized to evaluate their affinities and selectivities. The most potent of these Sn ligands, (4H-thieno[3,2-c]chromene-2-carbamoyl)-Neu5Ac alpha 2-3Gal beta 1-4GlcNAc ((TCC)Neu5Ac), was conjugated to lipids for display on a liposomal nanoparticle for evaluation of targeted delivery to cells. The (TCC)Neu5Ac liposomes were found to target liposomes selectively to cells expressing either murine or human Sn in vitro, and when administered to mice, they exhibited in vivo targeting to Sn-positive macrophages.

  DOI：

  10.1021/ja307501e

文献信息

• 一种CD169亲和三糖化合物及其制备方法
  申请人：厦门诺康得生物科技有限公司

  公开号：CN110041381A

  公开（公告）日：2019-07-23

  本发明公开了一种CD169亲和三糖化合物及其制备方法。本发明为针对CD169靶点，合成了一系列可靶向CD169+巨噬细胞的三糖化合物，并利用其对CD169亲和力最高的化合物对肿瘤、类风湿性关节炎和艾滋病病毒体内传播进行了尝试性治疗，效果显著。
• CD22 Ligands on a Natural <i>N</i>-Glycan Scaffold Efficiently Deliver Toxins to B-Lymphoma Cells
  作者：Wenjie Peng、James C. Paulson

  DOI：10.1021/jacs.7b03208

  日期：2017.9.13

  CD22 is a sialic acid-binding immunoglobulin-like lectin (Siglec) that is highly expressed on B-cells and B cell lymphomas, and is a validated target for antibody and nanoparticle based therapeutics. However, cell targeted therapeutics are limited by their complexity, heterogeneity, and difficulties in production. We describe here a chemically defined natural N-linked glycan scaffold that displays high affinity CD22 glycan ligands and outcompetes the natural ligand for the receptor, resulting in single molecule binding to CD22 and endocytosis into cells. Binding affinity is increased by up to 1500-fold compared to the monovalent ligand, while maintaining the selectivity for hCD22 over other Siglecs. Conjugates of these multivalent ligands with auristatin and saporin toxins are efficiently internalized via hCD22 resulting in killing of B-cell lymphoma cells. This single molecule ligand targeting strategy represents an alternative to antibody- and nanoparticle-mediated approaches for delivery of agents to cells expressing CD22 and other Siglecs.