6-(3-bromophenyl)-2-mercapto-4H-thiopyran-4-one | 500169-93-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 6-(3-bromophenyl)-2-mercapto-4H-thiopyran-4-one
• 英文别名: 6-(3-Bromophenyl)-2-mercapto-thiopyran-4-one；2-(3-bromophenyl)-6-sulfanylthiopyran-4-one
• CAS: 500169-93-7
• 化学式: C₁₁H₇BrOS₂
• 分子量: 299.212
• InChiKey: PKJAAIRVCCNFMI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  15
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  43.4
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-(3-bromophenyl)-2-mercapto-4H-thiopyran-4-one 在 四(三苯基膦)钯 potassium carbonate 作用下， 以 1,4-二氧六环 、 乙二醇 、 丙酮 为溶剂， 反应 92.0h， 生成 N-[2-[3-(6-morpholin-4-yl-4-oxothiopyran-2-yl)phenyl]phenyl]acetamide
  参考文献：
  名称：

  Pyranone, Thiopyranone, and Pyridone Inhibitors of Phosphatidylinositol 3-Kinase Related Kinases. Structure−Activity Relationships for DNA-Dependent Protein Kinase Inhibition, and Identification of the First Potent and Selective Inhibitor of the Ataxia Telangiectasia Mutated Kinase

  摘要：

  Structure-activity relationships have been investigated for inhibition of DNA-dependent protein kinase (DNA-PK) and ATM kinase by a series of pyran-2-ones, pyran-4-ones, thiopyran-4-ones, and pyridin-4-ones. A wide range of IC50 values were observed for pyranones and thiopyranones substituted at the 6-position, with the 3- and 5-positions proving intolerant to substitution. Related pyran-2-ones, pyran-4-ones, and thiopyran-4-ones showed similar IC50 values against DNA-PK, whereas the pyridin-4-one system proved, in general, ineffective at inhibiting DNA-PK. Extended libraries exploring the 6-position of 2-morpholino-pyran-4-ones and 2-morpholino-thiopyrano-4-ones identified the first highly potent and selective ATM inhibitor 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one (151C; ATM; IC50 = 13 nM) and revealed constrained SARs for ATM inhibition compared with DNA-PK. One of the most potent DNA-PK inhibitors identified, 2-(4-methoxyphenyl)-6-(morpholin-4-yl)pyran-4-one (16; DNA-PK; IC50 = 220 nM) effectively sensitized HeLa cells to the topoisomerase II inhibitor etoposide in vitro.

  DOI：

  10.1021/jm061121y
• 作为产物：
  描述：

  3'-溴苯乙酮 在 sodium ethanolate 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 生成 6-(3-bromophenyl)-2-mercapto-4H-thiopyran-4-one
  参考文献：
  名称：

  Pyranone, Thiopyranone, and Pyridone Inhibitors of Phosphatidylinositol 3-Kinase Related Kinases. Structure−Activity Relationships for DNA-Dependent Protein Kinase Inhibition, and Identification of the First Potent and Selective Inhibitor of the Ataxia Telangiectasia Mutated Kinase

  摘要：

  Structure-activity relationships have been investigated for inhibition of DNA-dependent protein kinase (DNA-PK) and ATM kinase by a series of pyran-2-ones, pyran-4-ones, thiopyran-4-ones, and pyridin-4-ones. A wide range of IC50 values were observed for pyranones and thiopyranones substituted at the 6-position, with the 3- and 5-positions proving intolerant to substitution. Related pyran-2-ones, pyran-4-ones, and thiopyran-4-ones showed similar IC50 values against DNA-PK, whereas the pyridin-4-one system proved, in general, ineffective at inhibiting DNA-PK. Extended libraries exploring the 6-position of 2-morpholino-pyran-4-ones and 2-morpholino-thiopyrano-4-ones identified the first highly potent and selective ATM inhibitor 2-morpholin-4-yl-6-thianthren-1-yl-pyran-4-one (151C; ATM; IC50 = 13 nM) and revealed constrained SARs for ATM inhibition compared with DNA-PK. One of the most potent DNA-PK inhibitors identified, 2-(4-methoxyphenyl)-6-(morpholin-4-yl)pyran-4-one (16; DNA-PK; IC50 = 220 nM) effectively sensitized HeLa cells to the topoisomerase II inhibitor etoposide in vitro.

  DOI：

  10.1021/jm061121y

文献信息

• Thiopyrane-4-ones as dna protein kinase inhibitors
  申请人：Martin Morrison Barr Niall

  公开号：US20050107367A1

  公开（公告）日：2005-05-19

  The present invention provides compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein R 1 and R 2 are independently hydrogen, an option ally substituted C 1-7 alkyl group, C 3-20 heterocyclyl group, or C 5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; and R 3 is an optionally substituted C 3-20 heterocyclyl or C 5-20 aryl group, and their use as pharmaceuticals, particularly in treating diseases which are retroviral mediated or ameliorated by the inhibition of DNA-PK,

  本发明提供了式（I）的化合物及其异构体、盐、溶剂合物、化学保护形式和前药，其中R1和R2独立地为氢、可选取代的C1-7烷基、C3-20杂环基或C5-20芳基，或者与它们连接的氮原子一起形成一个具有4至8个环原子的可选取代的杂环环；R3为可选取代的C3-20杂环基或C5-20芳基，以及它们在药物学中的应用，特别是在治疗由逆转录病毒介导或通过抑制DNA-PK改善的疾病中。
• Thiopyrane-4-ones as DNA protein kinase inhibitors
  申请人：Cancer Research Technology Limited

  公开号：US07105518B2

  公开（公告）日：2006-09-12

  The present invention provides compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, wherein R1 and R2 are independently hydrogen, an option ally substituted C1-7 alkyl group, C3-20 heterocyclyl group, or C5-20 aryl group, or may together form, along with the nitrogen atom to which they are attached, an optionally substituted heterocyclic ring having from 4 to 8 ring atoms; and R3 is an optionally substituted C3-20 heterocyclyl or C5-20 aryl group, and their use as pharmaceuticals, particularly in treating diseases which are retroviral mediated or ameliorated by the inhibition of DNA-PK,

  本发明提供了式（I）及其异构体，盐，溶剂合物，化学保护形式和前药的化合物，其中R1和R2分别为氢，可选择性取代的C1-7烷基，C3-20杂环基或C5-20芳基，或者可以与它们附着的氮原子一起形成具有4至8个环原子的可选择性取代的杂环环；而R3是可选择性取代的C3-20杂环或C5-20芳基，以及它们作为药物的用途，特别是用于治疗由逆转录病毒介导或通过抑制DNA-PK改善的疾病。
• 2,6-Disubstituted pyran-4-one and thiopyran-4-one inhibitors of DNA-Dependent protein kinase (DNA-PK)
  作者：Jonathan J. Hollick、Bernard T. Golding、Ian R. Hardcastle、Niall Martin、Caroline Richardson、Laurent J.M. Rigoreau、Graeme C.M. Smith、Roger J. Griffin

  DOI：10.1016/s0960-894x(03)00652-8

  日期：2003.9

  6-Aryl-2-morpholin-4-yl-4H-pyran-4-ones and 6-aryl-2-morpholin-4-yl-4H-thiopyran-4-ones were synthesised and evaluated as potential inhibitors of the DNA repair enzyme DNA-dependent protein kinase (DNA-PK). Several compounds in each series exhibited superior activity to the chromenone LY294002, and were of comparable potency to the benzochromenone NU7026 (IC50=0.23 muM). Importantly, members of both structural classes were found to be selective inhibitors of DNA-PK over related phosphatidylinositol 3-kinase-related kinase (PIKK) family members. A multiple-parallel synthesis approach, employing Suzuki cross-coupling methodology, was utilised to prepare libraries of thiopyran-4-ones with a range of aromatic groups at the 3'- and 4'-positions on the thiopyran-4-one 6-aryl ring. Screening of the libraries resulted in the identification of 6-aryl-2-morpholin-4-yl-4H-thiopyran-4-ones bearing naphthyl or benzo[b]thienyl substituents at the 4'-position, as potent DNA-PK inhibitors with IC50 values in the 0.2-0.4 muM range. (C) 2003 Elsevier Ltd. All rights reserved.
• THIOPYRANE-4-ONES AS DNA PROTEIN KINASE INHIBITORS
  申请人：CANCER RESEARCH TECHNOLOGY LIMITED

  公开号：EP1416936B1

  公开（公告）日：2005-06-01
• US7105518B2
  申请人：——

  公开号：US7105518B2

  公开（公告）日：2006-09-12