8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(pent-4-ynyl)adenine | 873436-90-9

• 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-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(pent-4-ynyl)adenine
• 英文别名: 8-(6-Iodobenzo[d][1,3]dioxol-5-ylthio)-9-(pent-4-ynyl)-9H-purin-6-amine；8-[(6-iodo-1,3-benzodioxol-5-yl)sulfanyl]-9-pent-4-ynylpurin-6-amine
• CAS: 873436-90-9
• 化学式: C₁₇H₁₄IN₅O₂S
• 分子量: 479.301
• InChiKey: QSNAITKZUCGADX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  113
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  8-巯基腺嘌呤 在 N-碘代丁二酰亚胺 、 copper(l) iodide 、 新铜试剂 、 caesium carbonate 、 三氟乙酸 、 sodium t-butanolate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 48.5h， 生成 8-(6-iodo-benzo[1,3]dioxol-5-ylsulfanyl)-9-(pent-4-ynyl)adenine
  参考文献：
  名称：

  Identification of Potent Water Soluble Purine-Scaffold Inhibitors of the Heat Shock Protein 90

  摘要：

  Hsp90 is a chaperone protein that allows cancer cells to tolerate the many components of dysregulated pathways. Its inactivation may result in targeting multiple molecular alterations and, thus, in reverting the transformed phenotype. The PU-class, a purine-scaffold Hsp90 inhibitor series, has been reported to be potent and selective against Hsp90 both in vitro and in vivo models of cancer. Here, a series of this 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. The study identifies water soluble derivatives (> 5 mM in PBS pH 7.4) of nanomolar potency (IC50 similar to 50 nM) in cellular and animal models of cancer. Binding affinities of these compounds for Hsp90 correlate well with their biological activities. When administered in vivo to mice bearing MDA-MB-468 human breast cancer xenocyrafted tumors, these agents result in pharmacologically relevant concentrations and, accordingly, in modulation of Hsp90-client proteins in tumors.

  DOI：

  10.1021/jm0508078

文献信息

• Small-Molecule Hsp90 Inhibitors
  申请人：Chiosis Gabriela

  公开号：US20080253965A1

  公开（公告）日：2008-10-16

  Hsp90 inhibitors are provided having the formula: with a 2′,4′,5′-substitution pattern on the right-side aryl moiety. X1 represents two substituents, which may be the same or different, disposed in the 4′ and 5′ positions on the aryl group, wherein X1 is selected from halogen, alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, pyrollyl, optionally substituted aryloxy, alkylamino, dialkylamino, carbamyl, amido, alkylamido dialkylamido, acylamino, alkylsulfonylamido, trihalomethoxy, trihalocarbon, thioalkyl, SO 2 . alkyl, COO-alkyl, KH 2 , OH, CN, SO 2 X 5 , NO 2 , NO, C═SR 2 NSO 2 X 5 , C═OR 2 , where X 5 is F, NH2, alkyl or H, and R 2 is alkyl, NH 2 , NH-alkyl or O-alkyl, C 1 to C 6 alkyl or alkoxy; or wherein X 1 has the formula -0-(CH 2 ) n -0-, wherein n is an integer from O to 2, preferably 1 or 2, and one of the oxygens is bonded at the 5′-position and the other at the 4′-position of the aryl ring. The compounds are useful in cancer therapy and as radioimaging ligands.

  提供具有以下公式的Hsp90抑制剂：右侧芳基基团上具有2'、4'、5'取代模式。X1代表位于芳基团的4'和5'位置的两个取代基，可以相同或不同，其中X1选自卤素、烷基、烷氧基、卤代烷氧基、羟基烷基、吡咯基、可选取代的芳氧基、烷基氨基、二烷基氨基、氨基甲酰、酰胺、烷基酰胺、二烷基酰胺、酰胺基、烷基磺酰胺基、三卤甲氧基、三卤代碳基、硫代烷基、SO2.烷基、COO-烷基、KH2、OH、CN、SO2X5、NO2、NO、C═SR2NSO2X5、C═OR2，其中X5为F、NH2、烷基或H，R2为烷基、NH2、NH-烷基或O-烷基，C1到C6烷基或烷氧基；或X1具有公式-0-（CH2）n-0-，其中n是0到2的整数，优选为1或2，其中一个氧原子与芳环的5'位置键合，另一个氧原子键合于4'位置。这些化合物在癌症治疗和放射性成像配体方面有用。
• Small-Molecule HSP90 Inhibitors
  申请人：Chiosis Gabriela

  公开号：US20110104054A1

  公开（公告）日：2011-05-05

  Hsp90 inhibitors having are provided having the formula: with a 2′,4′,5′-substitution pattern on the right-side aryl moiety. X1 represents two substituents, which may be the same or different, disposed in the 4′ and 5′ positions on the aryl group, wherein X1 is selected from halogen, alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, pyrollyl, optionally substituted aryloxy, alkylamino, dialkylamino, carbamyl, amido, alkylamido dialkylamido, acylamino, alkylsulfonylamido, trihalomethoxy, trihalocarbon, thioalkyl, SO 2- alkyl, COO-alkyl, KH 2 , OH, CN, SO 2 X 5 , NO 2 , NO, C═SR 2 NSO 2 X 5 , C═OR 2 , where X 5 is F, NH2, alkyl or H, and R 2 is alkyl, NH 2 , NH-alkyl or O-alkyl, C 1 to C 6 alkyl or alkoxy; or wherein X 1 has the formula -0-(CH 2 ) n -0-, wherein n is an integer from O to 2, preferably 1 or 2, and one of the oxygens is bonded at the 5′-position and the other at the 4′-position of the aryl ring. The compounds are useful in cancer therapy and as radioimaging ligands.

  提供具有以下公式的Hsp90抑制剂：右侧芳基基团上具有2′，4′，5′-取代模式。X1代表在芳基团上的4′和5′位置上排列的两个取代基，其中X1从卤素，烷基，烷氧基，卤代烷氧基，羟基烷基，吡咯基，可选择取代的芳氧基，烷基氨基，二烷基氨基，氨基甲酰，酰胺，烷基酰胺，二烷基酰胺，酰胺基，烷基磺酰胺基，三卤甲氧基，三卤代碳基，硫代烷基，SO2-烷基，COO-烷基，KH2，OH，CN，SO2X5，NO2，NO，C═SR2NSO2X5，C═OR2，其中X5为F，NH2，烷基或H，而R2为烷基，NH2，NH-烷基或O-烷基，C1到C6烷基或烷氧基；或其中X1具有公式-0-（CH2）n-0-，其中n是从O到2的整数，优选为1或2，其中一个氧原子与芳环的5′位置连接，另一个氧原子与芳环的4′位置连接。这些化合物在癌症治疗和放射成像配体中有用。
• Small-molecule Hsp90 Inhibitors
  申请人：Chiosis Gabriela

  公开号：US20110312980A1

  公开（公告）日：2011-12-22

  Purine scaffold Hsp90 inhibitors are useful in therapeutic applications and as radioimaging ligands.

  嘌呤支架Hsp90抑制剂在治疗应用和放射性成像配体中很有用。
• SMALL-MOLECULE HSP90 INHIBITORS
  申请人：MEMORIAL SLOAN KETTERING CANCER CENTER

  公开号：US20140227183A1

  公开（公告）日：2014-08-14

  Hsp90 inhibitors having are provided having the formula: (I) with a 2′,4′,5′-substitution pattern on the right-side aryl moiety. X1 represents two substituents, which may be the same or different, disposed in the 4′ and 5′ positions on the aryl group, wherein X1 is selected from halogen, alkyl, alkoxy, halogenated alkoxy, hydroxyalkyl, pyrollyl, optionally substituted aryloxy, alkylamino, dialkylamino, carbamyl, amido, alkylamido dialkylamido, acylamino, alkylsulfonylamido, trihalomethoxy, trihalocarbon, thioalkyl, SO 2 alkyl, COO-alkyl, KH 2 , OH, CN, SO 2 X 5 , NO 2 , NO, C═SR 2 NSO 2 X 5 , C═OR 2 , where X 5 is F, NH2, alkyl or H, and R 2 is alkyl, NH 2 , NH-alkyl or O-alkyl, C 1 to C 6 alkyl or alkoxy; or wherein X 1 has the formula —O—(CH 2 ) n —O—, wherein n is an integer from 0 to 2, preferably 1 or 2, and one of the oxygens is bonded at the 5′-position and the other at the 4′-position of the aryl ring. The compounds are useful in cancer therapy and as radioimaging ligands.

  提供具有公式（I）的Hsp90抑制剂，其在右侧芳基基团上具有2′，4′，5′-取代模式，其中X1表示两个取代基，可以相同或不同，分别位于芳基团的4′和5′位置，其中X1从卤素，烷基，烷氧基，卤代烷氧基，羟基烷基，吡咯基，可选取代的芳氧基，烷基氨基，二烷基氨基，氨基甲酰，酰胺，烷基酰胺，二烷基酰胺，乙酰氨基，烷基磺酰氨基，三卤代甲氧基，三卤代碳，硫代烷基，SO2烷基，COO-烷基，KH2，OH，CN，SO2X5，NO2，NO，C═SR2NSO2X5，C═OR2，其中X5为F，NH2，烷基或H，而R2为烷基，NH2，NH-烷基或O-烷基，C1至C6烷基或烷氧基；或其中X1具有公式—O—（CH2）n—O—，其中n是0到2之间的整数，优选为1或2，其中一个氧原子与芳环的5′位结合，另一个氧原子与芳环的4′位结合。这些化合物在癌症治疗和放射性成像配基方面有用。
• Small-molecule Hsp90 inhibitors
  申请人：Sloan-Kettering Institute for Cancer Research

  公开号：US10000494B2

  公开（公告）日：2018-06-19

  Purine scaffold Hsp90 inhibitors are useful in therapeutic applications and as radioimaging ligands.

  嘌呤支架 Hsp90 抑制剂可用于治疗和作为放射成像配体。