8-hydroxy-2-morpholin-4-yl-4H-1,3-benzoxazin-4-one | 1257411-46-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并恶嗪类
• 英文名称: 8-hydroxy-2-morpholin-4-yl-4H-1,3-benzoxazin-4-one
• 英文别名: 8-hydroxy-2-morpholin-4-yl-benzo[e][1,3]oxazin-4-one；8-hydroxy-2-morpholin-4-yl-1,3-benzoxazin-4-one
• CAS: 1257411-46-3
• 化学式: C₁₂H₁₂N₂O₄
• 分子量: 248.238
• InChiKey: LUDFEVXDXSPKGP-UHFFFAOYSA-N

物化性质

• 熔点：
  270 °C (decomp)(Solvent: Ethanol)
• 沸点：
  436.2±55.0 °C(Predicted)
• 密度：
  1.51±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  71.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-hydroxy-2-morpholin-4-yl-4H-1,3-benzoxazin-4-one 在 bis-triphenylphosphine-palladium(II) chloride 碳酸氢钠 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 为溶剂， 反应 1.0h， 生成 8-(4-amino-phenyl)-2-morpholin-4-yl-benzo[e][1,3]oxazin-4-one
  参考文献：
  名称：

  [EN] BENZO [E] [1, 3 ] OXAZIN-4-ONE DERIVATIVES AS PHOSPHOINOSITIDE 3-KINASE INHIBITORS
  [FR] DÉRIVÉS DE LA BENZO[E][1,3]OXAZIN-4-ONE EN TANT QU'INHIBITEURS DE LA PHOSPHOINOSITIDE 3-KINASE

  摘要：

  公式(I)的化合物，其中：W是O，N-H，N-烷基，N-烯基，N-炔基，N-芳基，N-杂芳基或S；每个X独立为CH或N；R1是公式(b)或R3是H，烷基，NH2，OH，=0或卤素；每个A和B独立为CH或N；D是NHR4；R4是H，烷基，-C(O)-烷基。-C(O)-NH2，-C(O)-NH-烷基，-SO2-烷基！，-SO2-NH2或-SO2-NH-烷基；R2是至少有一个含氮基团取代的芳基或R2是一个含氮杂芳基，用含氮基团取代的环烷基，含氮环烷基，C1-C6单烷基氨基，C1C6双烷基氨基，C1C6酰氨基，C1-C6氨基烷基，单(C1C6烷基)氨基C1-C6烷基，双(C1C6烷基)氨基C1C6烷基，C1-C6-酰氨基或C1 C6炔基-NR11；R11是H，烷基，烯基，炔基，芳基，杂芳基，卤素，O-烷基，NH-烷基，N-二烷基，-C(O)-R7，-C(O)-NH2，-C(O)-NH-R7，-SO2-R7，-SO2-NH2，-SO2-NH-R7，NH-酰基，NH-磺酰基，NR7-酰基，NR7-磺酰基，N-C(O)-NH-R7，N-SO2-NH-R7，N-C(O)-NR7R7或N-SO2-NR7R7；R7是烷基，芳基或杂芳基，可用作PI3K抑制剂，在治疗中有用。

  公开号：

  WO2011012883A1
• 作为产物：
  描述：

  吗啉 、 8-hydroxy-2-thioxo-2,3-dihydro-4H-benz[e]-1,3-oxazin-4-one 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以95%的产率得到8-hydroxy-2-morpholin-4-yl-4H-1,3-benzoxazin-4-one
  参考文献：
  名称：

  Synthesis, structural elucidation and DNA-dependant protein kinase and antiplatelet studies of 2-amino-[5, 6, 7, 8-mono and 7, 8-di-substituted]-1,3-benzoxazines

  摘要：

  A number of new 2-amino-[5, 6, 7 and 8]-O-substituted 1,3-benzoxazines, and 2-amino 8-methyl-7-O-substituted-1,3-benzoxazines were synthesized. Thirty one new compounds were tested for their effect on collagen induced platelet aggregation and it was found that the most active compounds were 8-methyl-2-morpholin-4-yl-7-(pyridin-3-ylmethoxy)-4H-1,3-benzoxazin-4-one 9f and 8-methyl-2-morpholin-4-yl-7-(pyridin-4-ylmethoxy)-4H-1,3-benzoxazin-4-one 9j with IC(50) = 2 +/- 1.5 and 4 +/- 2 mu M respectively. Inhibition of DNA-PK activity at concentrations of 1.6-4 mu M were tested for 9 products 5i, 7a-e and 9b, 9f and 9j. Crown Copyright (C) 2010 Published by Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2010.07.066

文献信息

• Benzo [E] [1,3] Oxazin-4-One Derivatives as Phosphoinositide 3-Kinase Inhibitors
  申请人：Shuttleworth Stephen Joseph

  公开号：US20120129848A1

  公开（公告）日：2012-05-24

  Compounds of formula (I): wherein: W is O, N—H, N-alkyl, N-alkenyl, N-alkynyl, N-aryl, N-heteroaryl or S; each X is independently CH or N; R 1 is formula (b) or R 3 is H, alkyl, NH 2 , OH, =0 or halogen; each A and B are independently CH or N; D is NHR 4 ; R 4 is H, alkyl, —C(O)— alkyl. —C(O)—NH 2 , —C(O)—NH— alkyl, —SO 2 — alkyl, —SO 2 —NH 2 or —SO 2 —NH— alkyl; R 2 is aryl substituted with at least one nitrogen-containing group or R 2 is a nitrogen-containing heteroaryl, cycloalkyl substituted with a nitrogen-containing group, nitrogen-containing cycloalkyl, C 1 -C 6 mono alkylamino, C 1 C 6 bis alkylamino, C 1 C 6 acylamino, C 1 -C 6 aminoalkyl, mono (C 1 C 6 alkyl) amino C 1 -C 6 alkyl, bis (C 1 C 6 alkyl) amino C 1 C 6 alkyl, C 1 -C 6 -acylamino or C 1 C 6 alkynyl-NR 11 , R 11 is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, halogen, O-alkyl, NH-alkyl, N-dialkyl, —C(O)—R 7 , —C(O)—NH 2 , —C(O)—NH—R 7 , —SO 2 —R 7 , —SO 2 —NH 2 , —SO 2 —NH—R 7 , NH-acyl, NH-sulfonyl, NR 7 -acyl, NR 7 -sulfonyl, N—C(O)—NH—R 7 , N—SO 2 —NH—R 7 , N—C(O)—NR 7 R 7 or N—SO 2 —NR 7 R 7 ; and R 7 is alkyl, aryl or heteroaryl, are useful as PI3K inhibitors and are useful in therapy.

  式(I)的化合物：其中：W为O，N—H，N-烷基，N-烯基，N-炔基，N-芳基，N-杂芳基或S；每个X独立地为CH或N；R1为式(b)或R3为H，烷基，NH2，OH，=0或卤素；每个A和B独立地为CH或N；D为NHR4；R4为H，烷基，—C（O）—烷基，—C（O）—NH2，—C（O）—NH—烷基，—SO2—烷基，—SO2—NH2或—SO2—NH—烷基；R2为芳基，其上至少有一个含氮基团或R2为含氮杂芳基，被氮基团取代的环烷基，含氮的环烷基，C1-C6单烷基氨基，C1-C6双烷基氨基，C1-C6酰胺基，C1-C6氨基烷基，单（C1-C6烷基）氨基C1-C6烷基，双（C1-C6烷基）氨基C1-C6烷基，C1-C6酰胺基或C1-C6炔基-NR11，R11为H，烷基，烯基，炔基，芳基，杂芳基，卤素，O-烷基，NH-烷基，N-二烷基，—C（O）—R7，—C（O）—NH2，—C（O）—NH—R7，—SO2—R7，—SO2—NH2，—SO2—NH—R7，NH-酰基，NH-磺酰基，NR7-酰基，NR7-磺酰基，N—C（O）—NH—R7，N—SO2—NH—R7，N—C（O）—NR7R7或N—SO2—NR7R7；且R7为烷基，芳基或杂芳基。这些化合物在PI3K抑制剂中有用，并且在治疗中有用。
• Benzo [E] [1,3] oxazin-4-one derivatives as phosphoinositide 3-kinase inhibitors
  申请人：Shuttleworth Stephen Joseph

  公开号：US08981087B2

  公开（公告）日：2015-03-17

  Compounds of formula (I): wherein: W is O, N—H, N-alkyl, N-alkenyl, N-alkynyl, N-aryl, N-heteroaryl or S; each X is independently CH or N; R1 is formula (b) or R3 is H, alkyl, NH2, OH, =0 or halogen; each A and B are independently CH or N; D is NHR4; R4 is H, alkyl, —C(O)-alkyl. —C(O)—NH2, —C(O)—NH-alkyl, —SO2-alkyl, —SO2—NH2 or —SO2—NH-alkyl; R2 is aryl substituted with at least one nitrogen-containing group or R2 is a nitrogen-containing heteroaryl, cycloalkyl substituted with a nitrogen-containing group, nitrogen-containing cycloalkyl, C1-C6 mono alkylamino, C1C6 bis alkylamino, C1C6 acylamino, C1-C6 aminoalkyl, mono (C1C6 alkyl)amino C1-C6 alkyl, bis (C1C6 alkyl)amino C1C6 alkyl, C1-C6-acylamino or C1 C6 alkynyl-NR11, R11 is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, halogen, O-alkyl, NH-alkyl, N-dialkyl, —C(O)—R7, —C(O)—NH2, —C(O)—NH—R7, —SO2—R7, —SO2—NH2, —SO2—NH—R7, NH-acyl, NH-sulfonyl, NR7-acyl, NR7-sulfonyl, N—C(O)—NH—R7, N—SO2—NH—R7, N—C(O)—NR7R7 or N—SO2—NR7R7; and R7 is alkyl, aryl or heteroaryl, are useful as PI3K inhibitors and are useful in therapy.

  式（I）的化合物：其中：W是O、N-H、N-烷基、N-烯基、N-炔基、N-芳基、N-杂环芳基或S；每个X独立地是CH或N；R1是式（b）或R3是H、烷基、NH2、OH、=0或卤素；每个A和B独立地是CH或N；D是NHR4；R4是H、烷基、-C（O）-烷基、-C（O）-NH2、-C（O）-NH-烷基、-SO2-烷基、-SO2-NH2或-SO2-NH-烷基；R2是芳基，其上至少有一个含氮基团，或R2是含氮杂环芳基、环烷基，其上带有含氮基团、含氮环烷基、C1-C6单烷基氨基、C1C6双烷基氨基、C1C6酰基氨基、C1-C6氨基烷基、单（C1C6烷基）氨基C1-C6烷基、双（C1C6烷基）氨基C1C6烷基、C1-C6-酰胺基或C1C6炔基-NR11，其中R11是H、烷基、烯基、炔基、芳基、杂环芳基、卤素、O-烷基、NH-烷基、N-二烷基、-C（O）-R7、-C（O）-NH2、-C（O）-NH-R7、-SO2-R7、-SO2-NH2、-SO2-NH-R7、NH-酰基、NH-磺酰基、NR7-酰基、NR7-磺酰基、N-C（O）-NH-R7、N-SO2-NH-R7、N-C（O）-NR7R7或N-SO2-NR7R7；R7是烷基、芳基或杂环芳基，可用作PI3K抑制剂，并且可用于治疗。
• BENZO[E][1,3]OXAZIN-4-ONE DERIVATIVES AS PHOSPHOINOSITIDE 3-KINASE INHIBITORS
  申请人：Karus Therapeutics Limited

  公开号：EP2459543B1

  公开（公告）日：2017-08-30
• US8981087B2
  申请人：——

  公开号：US8981087B2

  公开（公告）日：2015-03-17
• [EN] BENZO [E] [1, 3 ] OXAZIN-4-ONE DERIVATIVES AS PHOSPHOINOSITIDE 3-KINASE INHIBITORS<br/>[FR] DÉRIVÉS DE LA BENZO[E][1,3]OXAZIN-4-ONE EN TANT QU'INHIBITEURS DE LA PHOSPHOINOSITIDE 3-KINASE
  申请人：KARUS THERAPEUTICS LTD

  公开号：WO2011012883A1

  公开（公告）日：2011-02-03

  Compounds of formula (I): wherein: W is O, N-H, N-alky!, N-alkenyl, N-alkynyl, N-aryl, N-heteroaryl or S; each X is independently CH or N; R1 is formula (b) or R3 is H, alkyl, NH2, OH, =0 or halogen; each A and B are independently CH or N; D is NHR4; R4 is H, alkyl, -C(O)- alkyl. -C(O)-NH2, -C(O)-NH- alkyl, -SO2- alky!, -SO2-NH2 or -SO2-NH- alkyl; R2 is aryl substituted with at least one nitrogen-containing group or R2 is a nitrogen-containing heteroaryl, cycloalkyl substituted with a nitrogen-containing group, nitrogen-containing cycloalkyl, C1-C6 mono alkylamino, C1C6 bis alkylamino, C1C6 acylamino, C1-C6 aminoalkyl, mono (C1C6 alkyl) amino C1-C6 alkyl, bis (C1C6 alkyl) amino C1C6 alkyl, C1-C6-acylamino or C1 C6 alkynyl-NR11; R11 is H, alkyl, alkenyl, alkynyl, aryl, heteroaryl, halogen, O-alkyl, NH-alkyl, N-dialkyl, -C(O)-R7, -C(O)-NH2, -C(O)-NH-R7, -SO2-R7, -SO2-NH2, -SO2-NH- R7, NH-acyl, NH-sulfonyl, NR7-acyl, NR7-suIfonyl, N-C(O)-NH-R7, N-SO2-NH-R7, N-C(O)-NR7R7 or N-SO2-NR7R7; and R7 is alkyl, aryl or heteroaryl, are useful as PI3K inhibitors and are useful in therapy.

  公式(I)的化合物，其中：W是O，N-H，N-烷基，N-烯基，N-炔基，N-芳基，N-杂芳基或S；每个X独立为CH或N；R1是公式(b)或R3是H，烷基，NH2，OH，=0或卤素；每个A和B独立为CH或N；D是NHR4；R4是H，烷基，-C(O)-烷基。-C(O)-NH2，-C(O)-NH-烷基，-SO2-烷基！，-SO2-NH2或-SO2-NH-烷基；R2是至少有一个含氮基团取代的芳基或R2是一个含氮杂芳基，用含氮基团取代的环烷基，含氮环烷基，C1-C6单烷基氨基，C1C6双烷基氨基，C1C6酰氨基，C1-C6氨基烷基，单(C1C6烷基)氨基C1-C6烷基，双(C1C6烷基)氨基C1C6烷基，C1-C6-酰氨基或C1 C6炔基-NR11；R11是H，烷基，烯基，炔基，芳基，杂芳基，卤素，O-烷基，NH-烷基，N-二烷基，-C(O)-R7，-C(O)-NH2，-C(O)-NH-R7，-SO2-R7，-SO2-NH2，-SO2-NH-R7，NH-酰基，NH-磺酰基，NR7-酰基，NR7-磺酰基，N-C(O)-NH-R7，N-SO2-NH-R7，N-C(O)-NR7R7或N-SO2-NR7R7；R7是烷基，芳基或杂芳基，可用作PI3K抑制剂，在治疗中有用。