| 1094853-98-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• CAS: 1094853-98-1
• 化学式: C₃₃H₃₄O₅
• 分子量: 510.63
• InChiKey: HWUXVYXJMPDNDB-ZYWNIYNGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  38.0
• 可旋转键数：
  10.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  46.15
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  在 palladium 10% on activated carbon 、 氢气 、 2-叔丁基亚氨基-2-二乙基氨基-1,3-二甲基全氢-1,3,2-二氮杂磷 作用下， 以 乙醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 25.17h， 生成 (2R,2'R)-2,2'-((((2S,3R,5S)-3-methyltetrahydrofuran-2,5-diyl)bis-(2-methoxy-4,1-phenylene))bis(oxy))bis(1-(3,4-dimethoxyphenyl)propan-1-one)
  参考文献：
  名称：

  Evaluation of Manassantin A Tetrahydrofuran Core Region Analogues and Cooperative Therapeutic Effects with EGFR Inhibition

  摘要：

  Tumors adapt to hypoxia by regulating angiogenesis, metastatic potential, and metabolism. These adaptations mediated by hypoxia-inducible factor 1 (HIF-1) make tumors more aggressive and resistant to chemotherapy and radiation. Therefore, HIF-1 is a validated therapeutic target for cancer. In order to develop new HIF-1 inhibitors for cancer chemotherapy by harnessing the potential of the natural product manassantin A, we synthesized and evaluated manassantin A analogues with modifications in the tetrahydrofuran core region of manassantin A. Our structure-activity relationship study indicated that the alpha,alpha'-trans-configuration of the central ring of manassantin A is critical to HIF-1 inhibition. We also demonstrated that a combination of manassantin A with an epidermal growth factor receptor inhibitor shows cooperative antitumor activity (similar to 80% inhibition for combination vs similar to 30% inhibition for monotherapy). Our findings will provide important frameworks for the future therapeutic development of manassantin A-derived chemotherapeutic agents.

  DOI：

  10.1021/acs.jmedchem.0c00151
• 作为产物：
  描述：

  (2S,3R)-2-(4-(benzyloxy)-3-methoxyphenyl)-3-methyl-5-(phenylsulfonyl)tetrahydrofuran 、 [4-(benzyloxy)-3-methoxyphenyl]magnesium bromide 在 zinc dibromide 作用下， 以 四氢呋喃 为溶剂， 反应 0.5h， 以75%的产率得到
  参考文献：
  名称：

  Nucleophilic Addition of Organozinc Reagents to 2-Sulfonyl Cyclic Ethers: Stereoselective Synthesis of Manassantins A and B

  摘要：

  A convergent route to the synthesis of manassantins A and B, potent Inhibitors of HIF-1, is described. Central to the synthesis is a stereoselective addition of an organozinc reagent to a 2-benzenesulfonyl cyclic ether to achieve the 2,3-cis-3,4-trans-4,5-cis-tetrahydrofuran of the natural products. Preliminary structure-activity relationships suggested that the (R)-configuration at C-7 and C-7''' is not critical for HIF-1 inhibition. In addition, the hydroxyl group at C-7 and C-7''' can be replaced with a carbonyl group without loss of activity.

  DOI：

  10.1021/ol8024617

文献信息

• [EN] MANASSANTIN COMPOUNDS AND METHODS OF MAKING AND USING SAME<br/>[FR] COMPOSÉS DE MANASSANTIN ET LEURS PROCÉDÉS DE PRODUCTION ET D'UTILISATION
  申请人：UNIV DUKE

  公开号：WO2010059858A1

  公开（公告）日：2010-05-27

  Provided are manassantin compounds and methods of using the compounds. Provided are methods of treating a disease, the method comprising administering a compound according to Formula I. Further provided are pharmaceutical compositions comprising compounds according to Formula I. Also provided are methods of inhibiting HIF-1 in a cell, the methods comprising administering to the cell a compound according to Formula I.

  提供了manassantin化合物和使用该化合物的方法。提供了治疗疾病的方法，该方法包括给予符合公式I的化合物。另外提供了包含符合公式I的化合物的药物组合物。还提供了在细胞中抑制HIF-1的方法，该方法包括给予细胞符合公式I的化合物。