vizantin | 1223420-93-6

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 糖脂
• 英文名称: vizantin
• 英文别名: [(2R,3S,4S,5R,6R)-3,4,5-trihydroxy-6-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(3-nonyldodecanoyloxymethyl)oxan-2-yl]oxyoxan-2-yl]methyl 3-nonyldodecanoate
• CAS: 1223420-93-6
• 化学式: C₅₄H₁₀₂O₁₃
• 分子量: 959.396
• InChiKey: UQMXIEVSCRFPEI-PKTVYVHXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  15.7
• 重原子数：
  67
• 可旋转键数：
  44
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.96
• 拓扑面积：
  202
• 氢给体数：
  6
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  vizantin 在 三氧化硫 N,N-二甲基甲酰胺络合物 、 sodium acetate 作用下， 以 N,N-二甲基甲酰胺 、 乙醇 为溶剂， 以10.7 g的产率得到
  参考文献：
  名称：

  Vizantin 水溶性自组装类似物的开发

  摘要：

  Vizantin，6,6'-双-O- (3-壬基十二酰基)-α,α'-海藻糖，基于海藻糖 6,6'-二角霉菌酸酯的结构-活性关系研究，已被开发为一种安全的免疫刺激剂。我们最近的研究表明，vizantin 作为一种有效的 Toll 样受体 4 (TLR4) 部分激动剂，可降低脂多糖 (LPS) 引起的免疫休克的致死率。然而，由于维赞汀在水中的溶解度较低，体内测定系统中使用的水溶液在数十分钟内就会沉降。在此，对维赞汀进行了化学修饰，试图促进药物水溶液的制备。本文描述了水溶性 Vizantin 类似物的简明合成，其中糖单元的所有羟基都被硫酸盐取代。 Vizantin 衍生物在水中表现出胶束形成能力和有效的 TLR-4 部分激动剂活性。  全尺寸图像

  DOI：

  10.1248/cpb.c23-00716
• 作为产物：
  描述：

  6,6′-bis-O-(3-nonyldodecanoyl)-2,3,4,2′,3′,4′-hexabenzyl-α,α′-trehalose 在 palladium hydroxide, 20 wt% on carbon 、 氢气 作用下， 以 甲醇 、 氯仿 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 8.0h， 以77%的产率得到vizantin
  参考文献：
  名称：

  Development of Vizantin, a Safe Immunostimulant, Based on the Structure–Activity Relationship of Trehalose-6,6′-dicorynomycolate

  摘要：

  Vizantin, 6,6'-bis-O-(3-nonyldodecanoy1)-alpha,alpha'-trehalose, was developed as a safe immunostimulator on the basis of a structure-activity relationship (SAR) study with trehalose 6,6'-dicorynomycolate (TDCM). It was possible to synthesize vizantin on a large scale more easily than in the case of TDCM, and the compound exhibited more potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells. Because vizantin stimulated human macrophages, it is a promising candidate for clinical application.

  DOI：

  10.1021/jm3016443

文献信息

• Concise Synthesis of a Probe Molecule Enabling Analysis and Imaging of Vizantin
  作者：Hirofumi Yamamoto、Masataka Oda、Mayo Nakano、Kenta Yabiku、Masahiro Shibutani、Toshiyuki Nakanishi、Midori Suenaga、Masahisa Inoue、Hiroshi Imagawa、Masahiro Nagahama、Yoichi Matsunaga、Seiichiro Himeno、Kojun Setsu、Jun Sakurai、Mugio Nishizawa

  DOI：10.1248/cpb.c13-00006

  日期：——

  Trehalose 6,6′-dicorynomycolate (TDCM) was first characterized in 1963 as a cell surface glycolipid of Corynebacterium spp. by Ioneda and co-workers. TDCM shows potent anti-tumor activity due to its immunoadjuvant properties. Furthermore, the toxicity of TDCM in mice is much weaker than the related trehalose diester of mycolic acid; trehalose 6,6′-dimycolate (TDM, formerly known as cord factor). We have investigated the chemical modification of this class of compound to generate novel agents that display increased immunoadjuvant activity with minimal associated toxicity. During the course of this work we recently developed 6,6′-bis-O-(3-nonyldodecanoyl)-α,α′-trehalose (designated as vizantin). Our results show that vizantin exhibited a potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells without a loss of body weight and death in mice. Furthermore, vizantin effectively stimulated human macrophages in an in vitro model, making it a promising candidate for a safe adjuvant in clinical applications. In order to elucidate the pharmacokinetics of vizantin, a probe molecule with similar activity was developed on the basis of a structure–activity relationship (SAR) study with vizantin. The distribution of the probe molecule after intravenous administration into a mouse was assessed by macro confocal microscopy, where it was found to accumulate in the lungs and liver.

  Trehalose 6,6′-dicorynomycolate（TDCM）是由 Ioneda 及其合作者于 1963 年首次鉴定出的一种球孢子菌属细胞表面糖脂。由于其免疫佐剂特性，TDCM 具有很强的抗肿瘤活性。此外，TDCM 对小鼠的毒性比相关的霉菌酸曲卤糖二酯（6,6′-dimycolate 曲卤糖，以前称为脐带因子）要弱得多。我们一直在研究对这一类化合物进行化学修饰，以生产出能提高免疫佐剂活性且相关毒性最小的新型制剂。在这一研究过程中，我们最近开发出了 6,6′-双-O-（3-壬基十二碳酰基）-α,α′-曲哈洛糖（命名为 vizantin）。我们的研究结果表明，vizantin 对实验性 B16-F0 黑色素瘤细胞的肺转移具有有效的预防作用，且不会导致小鼠体重下降和死亡。此外，vizantin 还能在体外模型中有效刺激人体巨噬细胞，因此有望成为临床应用中的安全辅助剂。为了阐明 vizantin 的药代动力学，在对 vizantin 进行结构-活性关系（SAR）研究的基础上，开发了一种具有类似活性的探针分子。通过宏观共聚焦显微镜对小鼠静脉注射探针分子后的分布情况进行了评估，发现探针分子在肺部和肝脏中蓄积。
• EP2351764
  申请人：——

  公开号：——

  公开（公告）日：——
• Development of Vizantin, a Safe Immunostimulant, Based on the Structure–Activity Relationship of Trehalose-6,6′-dicorynomycolate
  作者：Hirofumi Yamamoto、Masataka Oda、Mayo Nakano、Naoyuki Watanabe、Kenta Yabiku、Masahiro Shibutani、Masahisa Inoue、Hiroshi Imagawa、Masahiro Nagahama、Seiichiro Himeno、Kojun Setsu、Jun Sakurai、Mugio Nishizawa

  DOI：10.1021/jm3016443

  日期：2013.1.10

  Vizantin, 6,6'-bis-O-(3-nonyldodecanoy1)-alpha,alpha'-trehalose, was developed as a safe immunostimulator on the basis of a structure-activity relationship (SAR) study with trehalose 6,6'-dicorynomycolate (TDCM). It was possible to synthesize vizantin on a large scale more easily than in the case of TDCM, and the compound exhibited more potent prophylactic effect on experimental lung metastasis of B16-F0 melanoma cells. Because vizantin stimulated human macrophages, it is a promising candidate for clinical application.
• Development of a Water Soluble Self-assembling Analogue of Vizantin
  作者：Mayo Nakano、Kyohei Sakamoto、Naoto Yamasaki、Yui Asano、Masataka Oda、Hironobu Takahashi、Takashige Kawakami、Masahisa Inoue、Hirofumi Yamamoto

  DOI：10.1248/cpb.c23-00716

  日期：2024.2.27

  vivo assay systems settles out in tens of minutes. Here, vizantin was chemically modified in an attempt to facilitate the preparation of an aqueous solution of the drug. This paper describes the concise synthesis of a water-soluble vizantin analogue in which all the hydroxyl groups of the sugar unit were replaced by sulfates. The vizantin derivative displayed micelle-forming ability in water and potent

  Vizantin，6,6'-双-O- (3-壬基十二酰基)-α,α'-海藻糖，基于海藻糖 6,6'-二角霉菌酸酯的结构-活性关系研究，已被开发为一种安全的免疫刺激剂。我们最近的研究表明，vizantin 作为一种有效的 Toll 样受体 4 (TLR4) 部分激动剂，可降低脂多糖 (LPS) 引起的免疫休克的致死率。然而，由于维赞汀在水中的溶解度较低，体内测定系统中使用的水溶液在数十分钟内就会沉降。在此，对维赞汀进行了化学修饰，试图促进药物水溶液的制备。本文描述了水溶性 Vizantin 类似物的简明合成，其中糖单元的所有羟基都被硫酸盐取代。 Vizantin 衍生物在水中表现出胶束形成能力和有效的 TLR-4 部分激动剂活性。  全尺寸图像