8-(3,4,5-trimethoxy-phenylsulfanyl)adenine | 827302-37-4

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 8-(3,4,5-trimethoxy-phenylsulfanyl)adenine
• 英文别名: 1H-Purin-6-amine, 8-[(3,4,5-trimethoxyphenyl)thio]-；8-(3,4,5-trimethoxyphenyl)sulfanyl-7H-purin-6-amine
• CAS: 827302-37-4
• 化学式: C₁₄H₁₅N₅O₃S
• 分子量: 333.371
• InChiKey: LMYMRNJBAALZRX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  134
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  8-(3,4,5-trimethoxy-phenylsulfanyl)adenine 在 N-碘代丁二酰亚胺 、 偶氮二甲酸二叔丁酯 、 三苯基膦 、 三氟乙酸 作用下， 以 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 1.5h， 生成 8-(2-Iodo-3,4,5-trimethoxy-phenylsulfanyl)-9-pent-4-ynyl-9H-purin-6-ylamine
  参考文献：
  名称：

  Evaluation of 8-Arylsulfanyl, 8-Arylsulfoxyl, and 8-Arylsulfonyl Adenine Derivatives as Inhibitors of the Heat Shock Protein 90

  摘要：

  Hsp90 is a chaperone protein with important roles in maintaining transformation and in elevating the survival and growth potential of cancer cells. Currently there is an increasing interest in developing inhibitors of this protein as anticancer therapeutics. One of such inhibitors, the purine-scaffold class, has been reported to be potent and selective against Hsp90 both in vitro and in vivo models of cancer. Here, a series of 8-arylsulfanyl, -sulfoxyl, and -sulfonyl adenine members of the purine class was synthesized and evaluated as inhibitors of the chaperone. The structure-activity relationship and selectivity for tumor Hsp90 of compounds within the series is presented. Our results suggest that 8-arylsulfanyl adenine derivatives are good inhibitors of chaperone activity, whereas oxidation of the sulfides to sulfoxides or sulfones leads to compounds of decreased activity. The study identifies derivative 11v as the most potent Hsp90 inhibitor of the purine-scaffold series published to date (EC50 = 30 nM), and also as the compound of this class with highest selectivity for tumor vs normal cell Hsp90 (700 to 3000-fold). Most rewardingly, this work has allowed for the identification of Hsp90 inhibitors with selective affinities for Hsp90-client protein complexes, derivatives that may represent useful pharmacological tools in dissecting Hsp90-regulated processes.

  DOI：

  10.1021/jm049012b
• 作为产物：
  描述：

  3,4,5-三甲氧基苯胺 在 盐酸 、 lithium aluminium tetrahydride 、 potassium carbonate 、 sodium nitrite 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 16.67h， 生成 8-(3,4,5-trimethoxy-phenylsulfanyl)adenine
  参考文献：
  名称：

  Evaluation of 8-Arylsulfanyl, 8-Arylsulfoxyl, and 8-Arylsulfonyl Adenine Derivatives as Inhibitors of the Heat Shock Protein 90

  摘要：

  Hsp90 is a chaperone protein with important roles in maintaining transformation and in elevating the survival and growth potential of cancer cells. Currently there is an increasing interest in developing inhibitors of this protein as anticancer therapeutics. One of such inhibitors, the purine-scaffold class, has been reported to be potent and selective against Hsp90 both in vitro and in vivo models of cancer. Here, a series of 8-arylsulfanyl, -sulfoxyl, and -sulfonyl adenine members of the purine class was synthesized and evaluated as inhibitors of the chaperone. The structure-activity relationship and selectivity for tumor Hsp90 of compounds within the series is presented. Our results suggest that 8-arylsulfanyl adenine derivatives are good inhibitors of chaperone activity, whereas oxidation of the sulfides to sulfoxides or sulfones leads to compounds of decreased activity. The study identifies derivative 11v as the most potent Hsp90 inhibitor of the purine-scaffold series published to date (EC50 = 30 nM), and also as the compound of this class with highest selectivity for tumor vs normal cell Hsp90 (700 to 3000-fold). Most rewardingly, this work has allowed for the identification of Hsp90 inhibitors with selective affinities for Hsp90-client protein complexes, derivatives that may represent useful pharmacological tools in dissecting Hsp90-regulated processes.

  DOI：

  10.1021/jm049012b

文献信息

• THERAPEUTIC COMPOUNDS AND THEIR USE IN CANCER
  申请人：Bajji C. Ashok

  公开号：US20070299258A1

  公开（公告）日：2007-12-27

  The invention relates to compounds of Formulae I-III and their therapeutic uses.

  这项发明涉及到I-III式化合物及其治疗用途。
• Therapeutic compounds and their use in cancer
  申请人：Myriad Pharmaceuticals, Inc.

  公开号：US07595401B2

  公开（公告）日：2009-09-29

  The invention relates to compounds of Formula I and their therapeutic uses, wherein substituent A is chosen from a substituted or unsubstituted aryl, heteroaryl, heterocyclic, or carboxylic group, B is chosen from a substituted or unsubstituted piperidine, homopiperidine, piperazine, pyrrolidine or azetidine group, R1 is chosen from hydro, alkyl, aryl, heteroaryl amino and halo, and L1 and L2 are as defined in the specification.

  本发明涉及I式化合物及其治疗用途，其中取代基A选择自取代或未取代的芳基、杂芳基、杂环基或羧基，取代基B选择自取代或未取代的哌啶基、同哌啶基、吡咯烷基或氮杂环基，R1选择自氢、烷基、芳基、杂芳基氨基和卤素，L1和L2如说明书所定义。
• Purine-core inhibitors of HSP90 and their use in treating cancer
  申请人：Bajji Ashok C.

  公开号：US08476285B2

  公开（公告）日：2013-07-02

  The invention relates to compounds of Formulae I-III: and therapeutic uses thereof, wherein A is chosen from a substituted or unsubstituted aryl, heteroaryl, heterocyclic, or carbocyclic group; B is chosen from a substituted or unsubstituted piperidine, homopiperidine, piperazine, pyrrolidine or azetidine group; R1 is chosen from hydro, alkyl, aryl, heteroaryl, amino, or halo; and L1, L2, are as defined herein.

  本发明涉及I-III式化合物及其治疗用途，其中A选择取代或未取代的芳基，杂芳基，杂环或碳环基；B选择取代或未取代的哌啶，同哌啶，吡咯烷或氮杂环基；R1选择氢、烷基、芳基、杂芳基、氨基或卤素；L1，L2定义如本文所述。
• Synthesis of 8-arylsulfoxyl/sulfonyl adenines
  作者：Laura Llauger、Huazhong He、Gabriela Chiosis

  DOI：10.1016/j.tetlet.2004.11.009

  日期：2004.12

  We report a method for the synthesis of 9-N-alkyl-8-arylsulfoxyl adenines and 9-N-alkyl-8-arylsulfonyl adenines. The approach starts with a tandem one-pot reaction that by using Mitsunobu conditions converts 8-arylsulfanyl adenines to the corresponding iminophosphorane protected 9-N-alkyl-8-arylsulfanyl adenines. These compounds were further subjected to selective OXONE(R)/alumina mediated oxidation followed by deprotection of the amine leading to the desired sulfoxides and sulfones. (C) 2004 Elsevier Ltd. All rights reserved.
• US7595401B2
  申请人：——

  公开号：US7595401B2

  公开（公告）日：2009-09-29