4H-1-苯并吡喃-4-酮,8-羟基-2-(4-吗啉基)- | 130735-95-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 中文名称: 4H-1-苯并吡喃-4-酮,8-羟基-2-(4-吗啉基)-
• 英文名称: 8-hydroxy-2-morpholin-4-yl-4H-chromen-4-one
• 英文别名: 8-hydroxy-2-(morpholin-4-yl)chromen-4-one；8-Hydroxy-2-(4-morpholinyl)-4H-1-benzopyran-4-one；8-hydroxy-2-morpholino-4H-chromen-4-one；2-(4-morpholinyl)-8-hydroxy-4H-1-benzopyran-4one；8-hydroxy-2-morpholine-4-yl-chromen-4-one；8-hydroxy-2-morpholin-4-ylchromen-4-one
• CAS: 130735-95-4
• 化学式: C₁₃H₁₃NO₄
• 分子量: 247.251
• InChiKey: FTTLDYBBQXGKRN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  4H-1-苯并吡喃-4-酮,8-羟基-2-(4-吗啉基)- 在 palladium diacetate 四丁基溴化铵 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 52.0h， 生成 2-吗啉代-8-苯基色酮
  参考文献：
  名称：

  磷脂酰肌醇3-激酶抑制剂LY294002及相关类似物的合成研究

  摘要：

  已经开发了用于直接和高产制备磷脂酰肌醇 3-激酶抑制剂 LY294002 的合成方法。这些方法很容易适用于有效生成类似物，这将有助于对这一重要的酶家族进行详细研究。

  DOI：

  10.1071/ch03113
• 作为产物：
  描述：

  4-乙酰基吗啉 在 三氟甲磺酸酐 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 4H-1-苯并吡喃-4-酮,8-羟基-2-(4-吗啉基)-
  参考文献：
  名称：

  PDE2 inhibition by the PI3 kinase inhibitor LY294002 and analogues

  摘要：

  Synthetic 2-morpholinochromones, including the known PI3-kinase inhibitor LY294002, have been evaluated in vitro as inhibitors of isolated human platelet phosphodiesterases. Inhibition of the cAMP-phosphodiesterases, PDE2 and PDE3 by LY294002 is reported for the first time. Preliminary screening across a range of 2-morpholinochromones has revealed structural features for optimised PDE2 inhibition. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.03.043

文献信息

• Judicious Application of Allyl Protecting Groups for the Synthesis of 2-Morpholin-4-yl-4-oxo-4<i>H</i>-chromen-8-yl Triflate, a Key Precursor of DNA-Dependent Protein Kinase Inhibitors
  作者：Sonsoles Rodriguez Aristegui、Marine Desage El-Murr、Bernard T. Golding、Roger J. Griffin、Ian R. Hardcastle

  DOI：10.1021/ol062297x

  日期：2006.12.1

  [Structure: see text] 2-morpholin-4-yl-4-oxo-4H-chromen-8-yl 2,2,2-trifluoromethanesulfonate is a key intermediate for the synthesis of the DNA-dependent protein kinase (DNA-PK) inhibitor 8-dibenzothiophen-4-yl-2-morpholin-4-yl-chromen-4-one (NU7441). Two improved methods for the synthesis of this triflate have been developed: (A) in 35% overall yield, through modification of the published route, and (B)

  [结构：见正文] 2-吗啉-4-基-4-氧代-4H-铬n-8-基2,2,2-三氟甲磺酸盐是合成DNA依赖性蛋白激酶（DNA-PK）的关键中间体）抑制剂8-二苯并噻吩-4-基-2-吗啉-4-基-铬基-4-酮（NU7441）。已开发出两种改进的合成三氟甲磺酸酯的方法：（A）通过修饰已公开的路线使总收率达到35％，（B）通过采用Baker-Venkataraman重排反应的新路线来提高总收率15％。能够生成色酮支架。两种合成都取决于对烯丙基保护基的明智使用。
• Potent enantioselective inhibition of DNA-dependent protein kinase (DNA-PK) by atropisomeric chromenone derivatives
  作者：Kate M. Clapham、Tommy Rennison、Gavin Jones、Faye Craven、Julia Bardos、Bernard T. Golding、Roger J. Griffin、Karen Haggerty、Ian R. Hardcastle、Pia Thommes、Attilla Ting、Céline Cano

  DOI：10.1039/c2ob26035b

  日期：——

  Substitution at the 7-position of the chromen-4-one pharmacophore of 8-(dibenzo[b,d]thiophen-4-yl)-2-morpholino-4H-chromen-4-one NU7441, a potent and selective DNA-dependent protein kinase (DNA-PK) inhibitor, with allyl, n-propyl or methyl enabled the resolution by chiral HPLC of atropisomers. Biological evaluation against DNA-PK of each pair of atropisomers showed a marked difference in potency, with

  取代在7位的chromen-4-one药效基团上 8-（二苯并[ b，d ]噻吩-4-基）-2-吗啉代-4 H-铬烯-4-一NU7441是一种有效的，选择性的DNA依赖性蛋白激酶（DNA-PK）抑制剂，具有烯丙基，正丙基或甲基，可以通过手性HPLC拆分阻转异构体。对每一对阻转异构体的DNA-PK的生物学评估显示，其效价存在显着差异，而生物学活性仅存在于Laororotatory对映异构体中。
• Therapeutic morpholino-substituted compounds
  申请人：——

  公开号：US20030216389A1

  公开（公告）日：2003-11-20

  Morpholino-substituted pyridopyrimidine, quinolone, and benzopyranone derivatives inhibit phosphoinositide (PI) 3-kinase, an enzyme that regulates platelet-adhesion processes. As a consequence, the compounds in question have anti-thrombotic activity, as well as other pharmaceutical properties. The compounds claimed are represented by formula (I), (II) and (III). PI 3-kinase generates 3-phosphorylated PI second messengers which stimulate platelet adhesion under blood-flow conditions. Because platelet adhesion is a necessary step in the formation of a thrombus, inhibition by these compounds of PI 3-kinase under such conditions inhibits or prevents thrombus formation. The compounds are useful in treating PI 3-kinase-dependent conditions including cardiovascular diseases such as coronary artery occlusion, stroke, acute coronary syndrome, acute myocardial infarction, vascular restenosis, atherosclerosis, and unstable angina; respiratory diseases such as asthma, chronic obstructive pulmonary diseases (COPD), and bronchitis; inflammatory disorders; neoplasms including cancers such as glioma, prostate cancer, small cell lung cancer, and breast cancer, and diseases linked to disordered white blood cell function, such as autoimmune and inflammatory diseases. 1

  Morpholino取代的吡啶并嘧啶、喹诺酮和苯并吡喃酮衍生物抑制磷脂酰肌醇(PI)3-激酶，这是一种调节血小板粘附过程的酶。因此，这些化合物具有抗血栓活性，以及其他药理特性。所声称的化合物由式(I)、(II)和(III)表示。PI3-激酶产生3-磷酸化PI第二信使，在血液流动条件下刺激血小板粘附。由于血小板粘附是血栓形成的一个必要步骤，这些化合物在这些条件下抑制PI3-激酶，从而抑制或防止血栓形成。这些化合物可用于治疗依赖PI3-激酶的疾病，包括心血管疾病，如冠状动脉闭塞、中风、急性冠状动脉综合征、急性心肌梗死、血管再狭窄、动脉粥样硬化和不稳定型心绞痛；呼吸系统疾病，如哮喘、慢性阻塞性肺病(COPD)和支气管炎；炎症性疾病；肿瘤，包括胶质瘤、前列腺癌、小细胞肺癌和乳腺癌等癌症，以及与白细胞功能紊乱相关的疾病，如自身免疫和炎症性疾病。
• SYNTHESIS OF 2-AMINO-SUBSTITUTED 4-OXO-4H-CHROMEN-8.YL-TRIFLUORO-METHANESULFONIC ACID ESTERS
  申请人：Griffin Roger John

  公开号：US20090326223A1

  公开（公告）日：2009-12-31

  A method of synthesising a compound of formula (I): wherein R N1 and R N2 are independently selected from 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; from a compound of formula (III): comprising the steps of: (a) removing the allyl group from the compound of formula (III) with appropriate reaction conditions to yield a compound of formula (II): and (b) reacting the compound of formula (II) with a triflating agent to yield a compound of formula (I).

  一种合成公式(I)化合物的方法：其中RN1和RN2分别选自氢、可选择取代的C1-7烷基、C3-20杂环基或C5-20芳基，或者与它们所连接的氮原子一起形成一个具有4到8个环原子的可选择取代的杂环环；从公式(III)化合物开始，包括以下步骤：(a)使用适当的反应条件去除公式(III)化合物的烯丙基，得到公式(II)化合物；(b)将公式(II)化合物与三氟甲烷磺酰化试剂反应，得到公式(I)化合物。
• Therapeutic Morpholino-Substituted Compounds
  申请人：Robertson Alan D.

  公开号：US20080206312A1

  公开（公告）日：2008-08-28

  Morpholino-substituted pyridopyrimidine, quinolone, and benzopyranone derivatives inhibit phosphoinositide (PI) 3-kinase, an enzyme that regulates platelet-adhesion processes. As a consequence, the compounds in question have anti-thrombotic activity, as well as other pharmaceutical properties. The compounds claimed are represented by formula (I), (II) and (III). PI 3-kinase generates 3-phosphorylated PI second messengers which stimulate platelet adhesion under blood-flow conditions. Because platelet adhesion is a necessary step in the formation of a thrombus, inhibition by these compounds of PI 3-kinase under such conditions inhibits or prevents thrombus formation. The compounds are useful in treating PI 3-kinase-dependent conditions including cardiovascular diseases such as coronary artery occlusion, stroke, acute coronary syndrome, acute myocardial infarction, vascular restenosis, atherosclerosis, and unstable angina; respiratory diseases such as asthma, chronic obstructive pulmonary diseases (COPD), and bronchitis; inflammatory disorders; neoplasms including cancers such as glioma, prostate cancer, small cell lung cancer, and breast cancer; and diseases linked to disordered white blood cell function, such as autoimmune and inflammatory diseases.

  Morpholino取代的吡啶并[3,4-d]吡嗪、喹诺酮和苯并吡喃衍生物抑制磷脂酰肌醇（PI）3-激酶，一种调节血小板粘附过程的酶。因此，所述化合物具有抗血栓活性以及其他药物性质。所要求的化合物由公式（I）、（II）和（III）表示。PI 3-激酶产生3-磷酸化PI第二信使，在血流条件下刺激血小板粘附。由于血小板粘附是形成血栓的必要步骤，这些化合物在这种条件下抑制PI 3-激酶会抑制或预防血栓形成。这些化合物可用于治疗PI 3-激酶依赖性疾病，包括心血管疾病，如冠状动脉闭塞、中风、急性冠状动脉综合症、急性心肌梗死、血管再狭窄、动脉粥样硬化和不稳定性心绞痛；呼吸系统疾病，如哮喘、慢性阻塞性肺疾病（COPD）和支气管炎；炎症性疾病；肿瘤，包括胶质瘤、前列腺癌、小细胞肺癌和乳腺癌等癌症；以及与白细胞功能紊乱有关的疾病，如自身免疫性和炎症性疾病。