(S)-1-(3,4-dimethoxyphenyl)-1-oxopropan-2-yl-4-methylbenzenesulfonate | 1094854-03-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (S)-1-(3,4-dimethoxyphenyl)-1-oxopropan-2-yl-4-methylbenzenesulfonate
• 英文别名: [(2S)-1-(3,4-dimethoxyphenyl)-1-oxopropan-2-yl] 4-methylbenzenesulfonate
• CAS: 1094854-03-1
• 化学式: C₁₈H₂₀O₆S
• 分子量: 364.419
• InChiKey: UUFFZYMQCZYDEA-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  87.3
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (S)-1-(3,4-dimethoxyphenyl)-1-oxopropan-2-yl-4-methylbenzenesulfonate 、 4-[(E)-2-(4-羟基-3-甲氧基苯基)乙烯基]-2-甲氧基苯酚 在 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 二氯甲烷 为溶剂， 反应 1.17h， 生成 (R)-1-(3,4-dimethoxyphenyl)-2-(4-((E)-4-(((R)-1-(3,4-dimethoxyphenyl)-1-oxopropan-2- yl)oxy)-3-methoxystyryl)-2-methoxyphenoxy)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：

  4-甲苯磺酸酐 、 (2S)-1-(3,4-dimethoxyphenyl)-2-hydroxypropan-1-one 在 吡啶 作用下， 反应 1.0h， 以87.7%的产率得到(S)-1-(3,4-dimethoxyphenyl)-1-oxopropan-2-yl-4-methylbenzenesulfonate
  参考文献：
  名称：

  三白脂素结构简化物，其制法和其药物组合物 与用途

  摘要：

  本发明公开了三白脂素结构简化物，其制法和其药物组合物与用途。具体涉及式I所示的通式(I)化合物或其异构体及其盐类，这类化合物的制备方法。一种新的药物组合物，包括有效剂量的式I化合物和药效学上可接受的载体。本发明还公开这类化合物用于制备预防和/或治疗肿瘤的药物中的应用。所述的肿瘤包括神经胶质母细胞瘤、黑色素瘤、胃癌、肺癌、乳腺癌、肾癌、肝癌、口腔表皮癌、宫颈癌、卵巢癌、胰腺癌、前列腺癌、结肠癌、直肠腺癌。

  公开号：

  CN102795975B

文献信息

• Design, synthesis of a novel 4-<i>O</i>-methylsaucerneol analogue LXY7824 as potent HIF-1 inhibitor and anti-cancer agent
  作者：Xiao-Yu Liu、Xiao-Yu Li、Fei-Long Yang、Yan Li、Xiao-Zhen Jiao、Ping Xie

  DOI：10.1080/10286020.2018.1473386

  日期：2018.6.3

  important transcription factor for tumor survival, is an attractive target for anti-cancer treatment. Herein, we present the design and synthesis of LXY7824, a simplified analogue of 4-O-methylsaucerneol. In addition, its significant HIF-1 inhibitory activity and potent anti-cancer activity in vivo and in vitro were also reported.

  缺氧诱导因子1（HIF-1）是肿瘤存活的重要转录因子，是抗癌治疗的诱人靶标。在这里，我们介绍LXY7824的设计和合成，LXY7824是4- O-甲基紫杉醇的简化类似物。此外，还报道了其在体内和体外显着的HIF-1抑制活性和有效的抗癌活性。
• [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。
• 咖啡酸苯乙酯类衍生物，其制法和其药物组合物与用途
  申请人：中国医学科学院药物研究所

  公开号：CN111777501B

  公开（公告）日：2022-09-16

  本发明公开了咖啡酸酯类衍生物及其制法和药物组合物与用途。具体涉及式(I)化合物或其异构体及其药学上可接受的盐，以及其制备方法。一种新的药物组合物，包括有效剂量的式(I)化合物和药效学上可接受的载体。本发明还公开了这类化合物在预防和/或治疗免疫失调，和/或肿瘤疾病方面的的应用。所述的肿瘤包括神经胶质母细胞瘤、黑色素瘤、胃癌、肺癌、乳腺癌、肾癌、肝癌、口腔表皮癌、宫颈癌、卵巢癌、胰腺癌、前列腺癌、结肠癌、直肠腺癌。
• Nucleophilic Addition of Organozinc Reagents to 2-Sulfonyl Cyclic Ethers: Stereoselective Synthesis of Manassantins A and B
  作者：Hyoungsu Kim、Amanda C. Kasper、Eui Jung Moon、Yongho Park、Ceshea M. Wooten、Mark W. Dewhirst、Jiyong Hong

  DOI：10.1021/ol8024617

  日期：2009.1.1

  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.
• Analysis of HIF-1 inhibition by manassantin A and analogues with modified tetrahydrofuran configurations
  作者：Amanda C. Kasper、Eui Jung Moon、Xiangqian Hu、Yongho Park、Ceshea M. Wooten、Hyoungsu Kim、Weitao Yang、Mark W. Dewhirst、Jiyong Hong

  DOI：10.1016/j.bmcl.2009.04.071

  日期：2009.7

  We have shown that manassantin A downregulated the HIF-1 alpha expression and inhibited the secretion of VEGF. We have also demonstrated that the 2,3-cis-3,4-trans-4,5-cis-configuration of the tetrahydrofuran is critical to the HIF-1 inhibition of manassantin A. (C) 2009 Elsevier Ltd. All rights reserved.