6-(3-methoxyphenyl)-2-(4-morpholinyl)-4H-pyran-4-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 6-(3-methoxyphenyl)-2-(4-morpholinyl)-4H-pyran-4-one
• 英文别名: 2-(3-methoxyphenyl)-6-morpholino-4H-pyran-4-one；2-(3-methoxyphenyl)-6-morpholin-4-ylpyran-4-one
• 化学式: C₁₆H₁₇NO₄
• 分子量: 287.315
• InChiKey: OLIONIBTYZDPMY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  48
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  4-乙酰基吗啉 在 甲烷磺酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正庚烷 、 乙基苯 为溶剂， 反应 1.75h， 生成 6-(3-methoxyphenyl)-2-(4-morpholinyl)-4H-pyran-4-one
  参考文献：
  名称：

  Synthesis of 2-Amino-6-phenyl-4H-pyran-4-ones

  摘要：

  一系列苯乙炔基β-酮酰胺与甲磺酸反应，高效地发生分子内环化，生成相应的2-氨基-6-苯基-4H-吡喃-4-酮。

  DOI：

  10.1055/s-1994-25402

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。
• 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.
• 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
  作者：Jonathan J. Hollick、Laurent J. M. Rigoreau、Celine Cano-Soumillac、Xiaoling Cockcroft、Nicola J. Curtin、Mark Frigerio、Bernard T. Golding、Sophie Guiard、Ian R. Hardcastle、Ian Hickson、Marc G. Hummersone、Keith A. Menear、Niall M. B. Martin、Ian Matthews、David R. Newell、Rachel Ord、Caroline J. Richardson、Graeme C. M. Smith、Roger J. Griffin

  DOI：10.1021/jm061121y

  日期：2007.4.1

  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.