phenyl 3,4-di-O-butyryl-2-O-benzyl-1-thio-α-L-rhamnopyranoside | 910041-16-6

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: phenyl 3,4-di-O-butyryl-2-O-benzyl-1-thio-α-L-rhamnopyranoside
• 英文别名: Phenyl 3,4-Di-O-butyryl-2-O-benzyl-1-thio-alpha-L-rhamnopyranoside；[(2S,3S,4R,5R,6S)-4-butanoyloxy-2-methyl-5-phenylmethoxy-6-phenylsulfanyloxan-3-yl] butanoate
• CAS: 910041-16-6
• 化学式: C₂₇H₃₄O₆S
• 分子量: 486.629
• InChiKey: TYIKAPDVSZTAOH-IHIAEKCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  96.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  phenyl 3,4-di-O-butyryl-2-O-benzyl-1-thio-α-L-rhamnopyranoside 在 溴 、 silver(l) oxide 作用下， 以 二氯甲烷 为溶剂， 反应 4.33h， 生成
  参考文献：
  名称：

  WO2007/139778

  摘要：

  公开号：
• 作为产物：
  描述：

  苯基-alpha-O-苄基-1-硫代-alpha-L-吡喃鼠李糖苷 、 丁酸酐 在 4-二甲氨基吡啶 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以100%的产率得到phenyl 3,4-di-O-butyryl-2-O-benzyl-1-thio-α-L-rhamnopyranoside
  参考文献：
  名称：

  Influence of rhamnose substituents on the potency of SL0101, an inhibitor of the Ser/Thr kinase, RSK

  摘要：

  We have previously reported the isolation of kaempferol 3-O-(3'',4"-di-O-acetyl-alpha-L-rhamnopyrano side) from Forsteronia refracta [Xu, Y.-M.; Smith, J. A.; Lannigan, D. A.; Hecht, S. M. Biorg. Med. Chem. 2006,14, 3974-3977.]. This flavonoid glycoside, termed SL0101, is a specific inhibitor of p90 ribosomal S6 kinase (RSK) with a dissociation constant of 1 mu M. In intact cells, however, the EC50 for inhibition of RSK activity is 50 mu M, which suggests that the efficacy of SL0101 could be limited by cellular uptake. Therefore, we investigated the possibility of developing a more potent RSK inhibitor by synthesizing SL0101 analogs with increased hydrophobic character. The total syntheses of kaempferol 3-O-(3",4"-di-O-butyryl-alpha-L-rhamnopyranoside) (Bu-SL0101) and kaempferol 3-O-(2",3",4"-tri-O-acetyl-alpha-L-rhamnopyranoside) (3Ac-SL0101) were performed. The IC50 for inhibition of RSK activity in in vitro kinase assays for the analogs was similar to that obtained for SL0101. 3Ac-SL0101 demonstrated the same remarkable specificity for inhibiting RSK activity in intact cells as SL0101; however, Bu-SL0101 was not completely specific. 3Ac-SL0101 was similar to 2-fold more potent at inhibiting MCF-7 cell proliferation compared to SL0101 and preferentially decreased MCF-7 cell growth, as compared to the growth of the normal human breast line, MCF-10A. Thus the discovery of 3Ac-SL0101 as a more potent RSK-specific inhibitor than SL0101 should facilitate the development of RSK inhibitors as anti-cancer chemotherapeutic agents. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2006.05.009

文献信息

• RHAMNOSE SUBSTITUENTS OF SL0101 AND THERAPEUTIC USES THEREOF
  申请人：Smith Jeffrey A.

  公开号：US20100016245A1

  公开（公告）日：2010-01-21

  The present invention provides compositions and methods useful for preparing and using analogs, derivatives, and modifications of kaempferols that have anti-neoplastic activity. More specifically, the compounds are analogs, derivatives, and modifications of SLO1O1. The invention further provides compounds that are inhibitors of rsk activity. The invention further provides compounds that selectively inhibit excessive rsk activity in cancers. The present invention further provides methods for treating cancer using compounds of the invention.

  本发明提供了用于制备和使用具有抗肿瘤活性的山柰酚的类似物、衍生物和修饰物的组合物和方法。更具体地说，这些化合物是SLO1O1的类似物、衍生物和修饰物。本发明还提供了抑制rsk活性的化合物。本发明还提供了在癌症中选择性抑制过度rsk活性的化合物。本发明还提供了使用本发明中的化合物治疗癌症的方法。
• Rhamnose substituents of SL0101 and therapeutic uses thereof
  申请人：Smith Jeffrey A.

  公开号：US08426568B2

  公开（公告）日：2013-04-23

  The present invention provides compositions and methods useful for preparing and using analogs, derivatives, and modifications of kaempferols that have anti-neoplastic activity. More specifically, the compounds are analogs, derivatives, and modifications of SLO1O1. The invention further provides compounds that are inhibitors of rsk activity. The invention further provides compounds that selectively inhibit excessive rsk activity in cancers. The present invention further provides methods for treating cancer using compounds of the invention.

  本发明提供了用于制备和使用具有抗肿瘤活性的山柰酚类似物、衍生物和修饰物的组合物和方法。更具体地说，这些化合物是SLO1O1的类似物、衍生物和修饰物。本发明还提供了抑制rsk活性的化合物。本发明还提供了在癌症中选择性抑制过度rsk活性的化合物。本发明还提供了使用本发明的化合物治疗癌症的方法。
• WO2007/139778
  申请人：——

  公开号：——

  公开（公告）日：——
• US8426568B2
  申请人：——

  公开号：US8426568B2

  公开（公告）日：2013-04-23
• Influence of rhamnose substituents on the potency of SL0101, an inhibitor of the Ser/Thr kinase, RSK
  作者：Jeffrey A. Smith、David J. Maloney、David E. Clark、Yaming Xu、Sidney M. Hecht、Deborah A. Lannigan

  DOI：10.1016/j.bmc.2006.05.009

  日期：2006.9

  We have previously reported the isolation of kaempferol 3-O-(3'',4"-di-O-acetyl-alpha-L-rhamnopyrano side) from Forsteronia refracta [Xu, Y.-M.; Smith, J. A.; Lannigan, D. A.; Hecht, S. M. Biorg. Med. Chem. 2006,14, 3974-3977.]. This flavonoid glycoside, termed SL0101, is a specific inhibitor of p90 ribosomal S6 kinase (RSK) with a dissociation constant of 1 mu M. In intact cells, however, the EC50 for inhibition of RSK activity is 50 mu M, which suggests that the efficacy of SL0101 could be limited by cellular uptake. Therefore, we investigated the possibility of developing a more potent RSK inhibitor by synthesizing SL0101 analogs with increased hydrophobic character. The total syntheses of kaempferol 3-O-(3",4"-di-O-butyryl-alpha-L-rhamnopyranoside) (Bu-SL0101) and kaempferol 3-O-(2",3",4"-tri-O-acetyl-alpha-L-rhamnopyranoside) (3Ac-SL0101) were performed. The IC50 for inhibition of RSK activity in in vitro kinase assays for the analogs was similar to that obtained for SL0101. 3Ac-SL0101 demonstrated the same remarkable specificity for inhibiting RSK activity in intact cells as SL0101; however, Bu-SL0101 was not completely specific. 3Ac-SL0101 was similar to 2-fold more potent at inhibiting MCF-7 cell proliferation compared to SL0101 and preferentially decreased MCF-7 cell growth, as compared to the growth of the normal human breast line, MCF-10A. Thus the discovery of 3Ac-SL0101 as a more potent RSK-specific inhibitor than SL0101 should facilitate the development of RSK inhibitors as anti-cancer chemotherapeutic agents. (c) 2006 Elsevier Ltd. All rights reserved.