9-(1-羟基乙基)-7-甲基-2-(吗啉-4-基)-4H-吡啶并[1,2-a]嘧啶-4-酮 | 1173900-35-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶并嘧啶类
• 中文名称: 9-(1-羟基乙基)-7-甲基-2-(吗啉-4-基)-4H-吡啶并[1,2-a]嘧啶-4-酮
• 中文别名: 9-(1-羟基乙基)-7-甲基-2-(吗啉-4-基)-4H-吡啶并[1,2-A]嘧啶-4-酮
• 英文名称: 9-(1-hydroxyethyl)-7-methyl-2-morpholino-4H-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: 9-(1-hydroxyethyl)-7-methyl-2-morpholinopyrido[1,2-a]pyrimidin-4-one；9-(1-hydroxyethyl)-7-methyl-2-morpholin-4-yl-4H-pyrido[1,2-a]pyrimidin-4-one；9-(1-hydroxyethyl)-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one
• CAS: 1173900-35-0
• 化学式: C₁₅H₁₉N₃O₃
• 分子量: 289.334
• InChiKey: VIXZNJXTMFRZSC-UHFFFAOYSA-N

物化性质

• 密度：
  1.35

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  65.4
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  9-(1-羟基乙基)-7-甲基-2-(吗啉-4-基)-4H-吡啶并[1,2-a]嘧啶-4-酮 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 25.0h， 生成 7-methyl-9-(1-(4-methylpiperazin-1-yl)ethyl)-2-morpholino-4H-pyrido[1,2-a]pyrimidin-4-one
  参考文献：
  名称：

  Synthesis of New TGX-221 Analogs

  摘要：

  TGX-221是一种强效的磷酸肌醇3-激酶（PI3K）β抑制剂，在治疗前列腺癌方面具有巨大的治疗潜力。研究人员对 TGX-221 的第 2 位和第 9 位进行了化学修饰。合成了5种新的TGX-221类似物，它们在2位和9位上具有吗啉、1-甲基哌嗪、苯胺和噻唑-2-胺等不同的杂环取代基。在 TGX-221 第 2 位和第 9 位的 SN2 置换反应中采用了平行合成方法。

  DOI：

  10.5560/znb.2014-4081
• 作为产物：
  描述：

  9-溴-2-羟基-7-甲基-4H-吡啶并[1,2-a]嘧啶-4-酮 在 盐酸 、 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 sodium tetrahydroborate 、 水 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 19.75h， 生成 9-(1-羟基乙基)-7-甲基-2-(吗啉-4-基)-4H-吡啶并[1,2-a]嘧啶-4-酮
  参考文献：
  名称：

  Synthesis of New TGX-221 Analogs

  摘要：

  TGX-221是一种强效的磷酸肌醇3-激酶（PI3K）β抑制剂，在治疗前列腺癌方面具有巨大的治疗潜力。研究人员对 TGX-221 的第 2 位和第 9 位进行了化学修饰。合成了5种新的TGX-221类似物，它们在2位和9位上具有吗啉、1-甲基哌嗪、苯胺和噻唑-2-胺等不同的杂环取代基。在 TGX-221 第 2 位和第 9 位的 SN2 置换反应中采用了平行合成方法。

  DOI：

  10.5560/znb.2014-4081

文献信息

• Enantiomerically Pure (-) 2-[1-(7-methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-A]pyrimidin-9-yl)ethylamino]benzoic Acid, Its Use In Medical Therapy, And A Pharmaceutical Composition Comprising It - 026
  申请人：Fjellstrom Ola

  公开号：US20090191177A1

  公开（公告）日：2009-07-30

  The present invention relates to enantiomerically pure (−) 2-[1-(7-methyl-2-(morpholin-4-yl)-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)ethylamino]benzoic acid or pharmaceutically acceptable salts thereof, it being in a solid state, its use in medical therapy, pharmaceutical composition comprising it, its use in the preparation of a medicament for use in a method for preventing or treating diseases, and its use in method for preventing or treating disease. The present invention relates to a selective inhibitor of phosphoinositide (PI) 3-kinase β and use of the selective inhibitor in e.g. anti-thrombotic therapy.

  本发明涉及对映纯的(−)2-[1-(7-甲基-2-(吗啡啉-4-基)-4-氧代-4H-吡啶[1,2-a]嘧啶-9-基)乙基氨基]苯甲酸或其药学上可接受的盐，其处于固态，以及其在医疗治疗中的用途，包含它的制药组合物，其在制备用于预防或治疗疾病的药物的方法中的用途，以及其在预防或治疗疾病的方法中的用途。本发明涉及选择性抑制磷脂酰肌醇(PI) 3-激酶β和使用该选择性抑制剂在抗血栓治疗中的用途。
• [EN] PHOSPHOINOSITIDE 3 KINASE BETA INHIBITORS AND COMPOSITIONS AND METHODS THEREOF<br/>[FR] INHIBITEURS DE LA PHOSPHOINOSITIDE 3 KINASE BÊTA ET COMPOSITIONS ET PROCÉDÉS ASSOCIÉS
  申请人：GEODE THERAPEUTICS INC

  公开号：WO2022164812A1

  公开（公告）日：2022-08-04

  The invention provides novel phosphoinositide 3 kinase beta- selective inhibitors and pharmaceutical compositions thereof, as well as methods of their preparation and use, in therapy of various diseases and conditions, such as solid tunors.

  该发明提供了一种新型的磷脂酰肌醇3激酶β选择性抑制剂及其制备和应用方法，用于治疗各种疾病和病况，例如实体肿瘤。同时还提供了相关的制药组合物。
• Prodrug Strategy for PSMA-Targeted Delivery of TGX-221 to Prostate Cancer Cells
  作者：Yunqi Zhao、Shaofeng Duan、Xing Zeng、Chunjing Liu、Neal M. Davies、Benyi Li、M. Laird Forrest

  DOI：10.1021/mp3000309

  日期：2012.6.4

  TGX-221 is a potent, selective, and cell membrane permeable inhibitor of the PI3K p110 beta catalytic subunit. Recent studies showed that TGX-221 has anti-proliferative activity against PTEN-deficient tumor cell lines including prostate cancers. The objective of this study was to develop an encapsulation system for parenterally delivering TGX-221 to the target tissue through a prostate-specific membrane aptamer (PSMAa10) with little or no side effects. In this study, PEG-PCL micelles were formulated to encapsulate the drug, and a prodrug strategy was pursued to improve the stability of the carrier system. Fluorescence imaging studies demonstrated that the cellular uptake of both drug and nanoparticles was significantly improved by targeted micelles in a PSMA positive cell line. The area under the plasma concentration time curve of the micelle formulation in nude mice was 2.27-fold greater than that of the naked drug, and the drug clearance rate was 6.16-fold slower. These findings suggest a novel formulation approach for improving site-specific drug delivery of a molecular-targeted prostate cancer treatment.
• Discovery of 9-(1-phenoxyethyl)-2-morpholino-4-oxo-pyrido[1,2-a]pyrimidine-7-carboxamides as oral PI3Kβ inhibitors, useful as antiplatelet agents
  作者：Fabrizio Giordanetto、Bernard Barlaam、Susanne Berglund、Karl Edman、Olle Karlsson、Jan Lindberg、Sven Nylander、Tord Inghardt

  DOI：10.1016/j.bmcl.2014.07.007

  日期：2014.8

  Optimization of AZD6482 (2), the first antiplatelet PI3K beta inhibitor evaluated in man, focused on improving the pharmacokinetic profile to a level compatible with once daily oral dosing as well as achieving adequate selectivity towards PI3K alpha to minimize the risk for insulin resistance. Structure-based design and optimization of DMPK properties resulted in (R)-16, a novel, orally bioavailable PI3K beta inhibitor with potent in vivo anti-thrombotic effect with excellent separation to bleeding risk and insulin resistance. (C) 2014 Elsevier Ltd. All rights reserved.