8-(3-methoxyphenylsulfanyl)-9H-purin-6-ylamine | 696574-58-0

• 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-methoxyphenylsulfanyl)-9H-purin-6-ylamine
• 英文别名: 8-(3-methoxy-phenylsulfanyl)adenine；8-(3-methoxyphenylsulfanyl)adenine；8-(3-Methoxyphenylthio)-9H-purin-6-amine；8-[(3-Methoxyphenyl)sulfanyl]-7H-purin-6-amine；8-(3-methoxyphenyl)sulfanyl-7H-purin-6-amine
• CAS: 696574-58-0
• 化学式: C₁₂H₁₁N₅OS
• 分子量: 273.318
• InChiKey: MAMYZXXYNCBLHY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-(3-methoxyphenylsulfanyl)-9H-purin-6-ylamine 在 盐酸 、 叔丁基过氧化氢 、 偶氮二甲酸二叔丁酯 、 三苯基膦 作用下， 以 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 0.5h， 生成 8-(2,4-Dichloro-5-methoxy-phenylsulfanyl)-9-(2-isopropoxy-ethyl)-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：

  腺嘌呤 在 溴 、 potassium carbonate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 8-(3-methoxyphenylsulfanyl)-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

文献信息

• HSP90 Inhibitors Containing a Zinc Binding Moiety
  申请人：Qian Changgeng

  公开号：US20080234297A1

  公开（公告）日：2008-09-25

  The present invention relates to HSP90 inhibitors and their use in the treatment of cell proliferative diseases such as cancer. The said derivatives may further act as HDAC inhibitors.

  本发明涉及HSP90抑制剂及其在治疗癌症等细胞增殖性疾病中的应用。所述衍生物还可能作为HDAC抑制剂。
• General Method for the Synthesis of 8-Arylsulfanyl Adenine Derivatives
  作者：Huazhong He、Laura Llauger、Neal Rosen、Gabriela Chiosis

  DOI：10.1021/jo049875c

  日期：2004.4.1

  We report a general method for the synthesis of 8-arylsulfanyl adenine derivatives using a mild protocol of coupling 8-mercaptoadenine with a variety of aryl iodides.

  我们报告了使用8-巯基腺嘌呤与各种芳基碘偶联的温和协议合成8-芳基硫烷基腺嘌呤衍生物的一般方法。
• Preparation of 8-(Arylsulfanyl)adenines with Diazonium Salts under Mild, Aerobic Conditions
  作者：Marco A. Biamonte、Jiandong Shi、David Hurst、Kevin Hong、Marcus F. Boehm、Srinivas R. Kasibhatla

  DOI：10.1021/jo048522a

  日期：2005.1.1

  Benzenediazonium ions carrying an electron-withdrawing substituent gave the highest yields. The reaction proceeded smoothly at room temperature without any base and could be performed under air atmosphere. The extremely mild conditions are compatible with a wide range of functional groups.

  8-（芳基硫基）腺嘌呤11是在高达75％的收率由8- thionoadenine反应制备6（乙酸3-（6-氨基-8-硫代-7,8- dihydropurin -9-基）丙基酯）与DMSO中的四氟硼酸苯重氮盐。带有吸电子取代基的苯二氮杂zon离子的收率最高。该反应在室温下没有任何碱的条件下平稳进行，可以在空气气氛下进行。极端温和的条件可与各种官能团兼容。
• Multi-Functional Small Molecules as Anti-Proliferative Agents
  申请人：Cai Xiong

  公开号：US20080221132A1

  公开（公告）日：2008-09-11

  The present invention relates to the compositions, methods, and applications of a novel approach to selective inhibition of several cellular or molecular targets with a single small molecule. More specifically, the present invention relates to multi-functional small molecules wherein one functionality is capable of inhibiting histone deacetylases (HDAC) and the other functionality is capable of inhibiting a different cellular or molecular pathway involved in aberrant cell proliferation, differentiation or survival.

  本发明涉及一种新型选择性抑制多种细胞或分子靶点的组合物、方法和应用。更具体地说，本发明涉及多功能小分子，其中一种功能能够抑制组蛋白去乙酰化酶（HDAC），另一种功能能够抑制与异常细胞增殖、分化或存活有关的不同细胞或分子途径。
• 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.