4-Hydroxy-2H-naphtho<1,2-b>pyran-2-thione | 173210-13-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并呋喃类
• 英文名称: 4-Hydroxy-2H-naphtho<1,2-b>pyran-2-thione
• 英文别名: 4-hydroxybenzo[h]chromen-2-thione
• CAS: 173210-13-4
• 化学式: C₁₃H₈O₂S
• 分子量: 228.271
• InChiKey: KBFFYCKMFRGXSS-UHFFFAOYSA-N

物化性质

• 沸点：
  409.9±55.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.02
• 重原子数：
  16.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  33.37
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  4-Hydroxy-2H-naphtho<1,2-b>pyran-2-thione 在 potassium carbonate 作用下， 以 乙二醇 、 丙酮 为溶剂， 反应 5.0h， 生成 2-(3-Hydroxy-pyrrolidin-1-yl)-benzo[h]chromen-4-one
  参考文献：
  名称：

  DNA依赖性蛋白激酶的选择性苯并吡喃酮和嘧啶[2,1-a]异喹啉-4-酮抑制剂：合成，结构活性研究和体外人类肿瘤细胞系的放射增敏作用。

  摘要：

  合成了各种各样的chromen-2-one，chromen-4-one和pyrimidoisoquinolin-4-one衍生物，并评估了其对DNA修复酶DNA依赖性蛋白激酶（DNA-PK）的抑制活性，目的是阐明效价和激酶选择性的构效关系。DNA-PK抑制活性在评估的一系列化合物（IC（50）值范围从0.19到> 10 microM）上有很大差异，其中7,8-苯并铬基-4-酮和嘧啶基[2,1]表现出优异的活性。 -a] isoquinolin-4-one模板。相比之下，基于苯并色素-2-酮（香豆素）或2-芳基-7,8-苯并色素-4-酮（黄酮）支架的抑制剂效力较低。至关重要的是，这些研究揭示了在苯并吡喃酮和嘧啶基2位上的结构活性关系非常受约束[2，1-a]异喹啉-4-酮药效基团，在此位置仅可耐受2-吗啉代或2-（2'-甲基吗啉代）基团。用最有效的抑制剂NU7163（48; IC（50）= 0

  DOI：

  10.1021/jm049526a
• 作为产物：
  描述：

  二硫化碳 、 2-乙酰基-1-萘酚 在 potassium tert-butylate 、 硫酸 作用下， 以 甲苯 为溶剂， 反应 32.0h， 以29%的产率得到4-Hydroxy-2H-naphtho<1,2-b>pyran-2-thione
  参考文献：
  名称：

  DNA依赖性蛋白激酶的选择性苯并吡喃酮和嘧啶[2,1-a]异喹啉-4-酮抑制剂：合成，结构活性研究和体外人类肿瘤细胞系的放射增敏作用。

  摘要：

  合成了各种各样的chromen-2-one，chromen-4-one和pyrimidoisoquinolin-4-one衍生物，并评估了其对DNA修复酶DNA依赖性蛋白激酶（DNA-PK）的抑制活性，目的是阐明效价和激酶选择性的构效关系。DNA-PK抑制活性在评估的一系列化合物（IC（50）值范围从0.19到> 10 microM）上有很大差异，其中7,8-苯并铬基-4-酮和嘧啶基[2,1]表现出优异的活性。 -a] isoquinolin-4-one模板。相比之下，基于苯并色素-2-酮（香豆素）或2-芳基-7,8-苯并色素-4-酮（黄酮）支架的抑制剂效力较低。至关重要的是，这些研究揭示了在苯并吡喃酮和嘧啶基2位上的结构活性关系非常受约束[2，1-a]异喹啉-4-酮药效基团，在此位置仅可耐受2-吗啉代或2-（2'-甲基吗啉代）基团。用最有效的抑制剂NU7163（48; IC（50）= 0

  DOI：

  10.1021/jm049526a

文献信息

• [EN] DNA-PK INHIBITORS<br/>[FR] INHIBITEURS D'ADN-PK
  申请人：CANCER REC TECH LTD

  公开号：WO2003024949A1

  公开（公告）日：2003-03-27

  The invention relates to the use of compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, in the preparation of a medicament for inhibiting the activity of DNA-PK, wherein R?1 and R2¿ are independently hydrogen, an optionally substituted C¿1-7? 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; X and Y are selected from CR?4¿ and O, O and CR'4 and NR'4 and N, where the unsaturation is in the appropriate place in the ring, and where one of R?3 and R4 or R'4¿ is an optionally substituted C¿3-20? heteroaryl or C5-20 aryl group, and the other of R?3 and R4 or R'4¿ is H, or R?3 and R4 or R'4¿ together are -A-B-, which collectively represent a fused optionally substituted aromatic ring. The compounds also selectively inhibit the activity of DNA-PK compared to PI 3-kinase and/or ATM.

  本发明涉及使用式(I)化合物及其异构体、盐、溶剂合物、化学保护形式和前药，在制备用于抑制DNA-PK活性的药物中使用，其中R?1和R2¿分别为氢、可选取代的C¿1-7?烷基、C3-20杂环基或C5-20芳基，或者可以与它们连接的氮原子一起形成具有4到8个环原子的可选取代杂环环；X和Y从CR?4¿和O、O和CR'4和NR'4和N中选取，其中不饱和度在环中适当位置，其中R?3和R4或R'4¿中的一个为可选取代的C¿3-20?杂芳基或C5-20芳基，而另一个为H，或者R?3和R4或R'4¿一起是-A-B-，它们共同代表一个融合的可选取代芳香环。这些化合物还比PI 3-激酶和/或ATM选择性地抑制DNA-PK活性。
• Dna-pk inhibitors
  申请人：——

  公开号：US20040192687A1

  公开（公告）日：2004-09-30

  The invention relates to the use of compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, in the preparation of a medicament for inhibiting the activity of DNA-PK, wherein R 1 and R 2 are independently hydrogen, an optionally 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; X and Y are selected from CR 4 and O, O and CR′ 4 and NR″ 4 and N, where the unsaturation is in the appropriate place in the ring, and where one of R 3 and R 4 or R′ 4 is an optionally substituted C 3-20 heteroaryl or C 5-20 aryl group, and the other of R 3 and R 4 or R′ 4 is H, or R 3 and R 4 or R″ 4 together are —A—B—, which collectively represent a fused optionally substituted aromatic ring. The compounds also selectively inhibit the activity of DNA-PK compared to PI 3-kinase and/or ATM. 1

  本发明涉及使用式(I)化合物及其异构体、盐、溶剂合物、化学保护形式及其前药，在制备抑制DNA-PK活性的药物方面使用。其中，R1和R2分别为氢、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含有4到8个环原子的可选取代杂环环；X和Y从CR4和O、O和CR'4以及NR"4和N中选择，其中不饱和度在环中适当位置，且R3和R4或R'4中的一个为可选取代的C3-20杂芳基或C5-20芳基，而另一个为氢，或者R3和R4或R"4一起为-A-B-，它们共同表示一个融合的可选取代芳香环。这些化合物与PI 3-激酶和/或ATM相比，也具有选择性抑制DNA-PK活性的作用。
• DNA-PK INHIBITORS
  申请人：Martin Morrison Barr Niall

  公开号：US20070238729A1

  公开（公告）日：2007-10-11

  The invention relates to the use of compounds of formula (I) and isomers, salts, solvates, chemically protected forms, and prodrugs thereof, in the preparation of a medicament for inhibiting the activity of DNA-PK, wherein R 1 and R 2 are independently hydrogen, an optionally 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; X and Y are selected from CR 4 and O, O and CR′ 4 and NR″ 4 and N, where the unsaturation is in the appropriate place in the ring, and where one of R 3 and R 4 or R′ 4 is an optionally substituted C 3-20 heteroaryl or C 5-20 aryl group, and the other of R 3 and R 4 or R′ 4 is H, or R 3 and R 4 or R″ 4 together are -A-B—, which collectively represent a fused optionally substituted aromatic ring. The compounds also selectively inhibit the activity of DNA-PK compared to PI 3-kinase and/or ATM.

  本发明涉及使用式(I)的化合物及其异构体、盐、溶剂合物、化学保护形式和前药，在制备抑制DNA-PK活性的药物方面有用。其中，R1和R2独立地表示氢、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可选取代的含有4到8个环原子的杂环环；X和Y选自CR4和O，O和CR'4以及NR"4和N，其中不饱和度在环中适当位置，其中R3和R4或R'4中的一个为可选取代的C3-20杂芳基或C5-20芳基，而另一个为H，或者R3和R4或R"4在一起为-A-B-，代表一种融合的可选取代芳香环。这些化合物与PI 3-激酶和/或ATM相比，具有选择性地抑制DNA-PK的活性。
• Discovery of Potent Chromen-4-one Inhibitors of the DNA-Dependent Protein Kinase (DNA-PK) Using a Small-Molecule Library Approach
  作者：Ian R. Hardcastle、Xiaoling Cockcroft、Nicola J. Curtin、Marine Desage El-Murr、Justin J. J. Leahy、Martin Stockley、Bernard T. Golding、Laurent Rigoreau、Caroline Richardson、Graeme C. M. Smith、Roger J. Griffin

  DOI：10.1021/jm050444b

  日期：2005.12.1

  Structure-activity relationships for inhibition of DNA-dependent protein kinase (DNA-PK) have been defined for substituted chromen-4-ones. For the 2-amino-substituted benzo[h]chromen-4-ones, a morpholine substituent at this position was essential for activity. Small libraries of 6- and 7-alkoxy-substituted chromen-4-ones showed that a number of 7-alkoxysubstituted chromenones displayed improved activity. Focused libraries incorporating 6-, 7-, and 8-aryl and heteroaryl substituents were prepared. In these cases, 6- and 7-substitution was disfavored, whereas 8-substitution was largely tolerated. Surprisingly, two compounds, 2-N-morpholino-8-dibenzofuranyl-chromen-4-one (NU7427, 3238}) and the 2-N-morpholino-8-dibenzothiophenyl-chromen-4-one (NU7441, 3226}) were excellent inhibitors (IC50 vs DNAPK = 40 and 13 nM, respectively). The ring-saturated analogue 2-N-morpholino-8-(6',7',8',9'-tetrahydrodibenzothiophene)chromen-4-one, 36, retained potent activity (IC50 vs DNA-PK = 23 nM). The dibenzothiophene 3238} sensitized HeLa cells to ionizing radiation in vitro, with dose modification factors of 2.5 at 10% survival being observed at 0.5 mu M. The cytotoxicity of the topoisomerase II inhibitor etoposide was also potentiated.
• Di Braccio; Roma; Leoncini, Il Farmaco, 1995, vol. 50, # 10, p. 703 - 711
  作者：Di Braccio、Roma、Leoncini、Poggi

  DOI：——

  日期：——