9-溴-7-甲基-2-(4-吗啉基)-4H-吡啶并[1,2-a]嘧啶-4-酮 | 351002-16-9

• 物质功能分类: 医药中间体 - 吡啶类化合物
• 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-溴-7-甲基-2-(4-吗啉基)-4H-吡啶并[1,2-a]嘧啶-4-酮
• 中文别名: 9-溴-7-甲基-2-(4-吗啉基)-4H-吡啶并[1,2-A]嘧啶-4-酮
• 英文名称: 9-bromo-7-methyl-2-morpholino-4H-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: TGX066；9-bromo-7-methyl-2-morpholin-4-ylpyrido[1,2-a]pyrimidin-4-one
• CAS: 351002-16-9
• 化学式: C₁₃H₁₄BrN₃O₂
• 分子量: 324.177
• InChiKey: CUSBPCYPCUDPSC-UHFFFAOYSA-N

物化性质

• 沸点：
  447.3±55.0 °C(Predicted)
• 密度：
  1.63

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  45.1
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 海关编码：
  2934999090
• 危险性防范说明：
  P261,P280,P301+P312,P302+P352,P305+P351+P338
• 危险性描述：
  H302,H315,H320,H335
• 储存条件：
  室温

反应信息

• 作为反应物：
  描述：

  9-溴-7-甲基-2-(4-吗啉基)-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 19.5h， 生成 1-(7-methyl-2-morpholino-4-oxo-4H-pyrido[1,2-a]pyrimidin-9-yl)ethyl methanesulfonate
  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：

  2-氨基-5-甲基吡啶 在 溴 、 sodium acetate 、 溶剂黄146 、 甲基磺酰氯 、 三乙胺 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 26.0h， 生成 9-溴-7-甲基-2-(4-吗啉基)-4H-吡啶并[1,2-a]嘧啶-4-酮
  参考文献：
  名称：

  Exploring the isoform selectivity of TGX-221 related pyrido[1,2-a]pyrimidinone-based Class IA PI 3-kinase inhibitors: Synthesis, biological evaluation and molecular modelling

  摘要：

  A novel series of TGX-221 analogues was prepared and tested for their potency against the p110 alpha, p110 beta, and p110 delta isoforms of the PI3K enzyme, and in two cellular assays. The biological results were interpreted in terms of a p110 beta comparative model, in order to account for their selectivity towards this isoform. A CH2NH type linker is proposed to allow binding into the specificity pocket proposed to accommodate the high p110 beta-selectivity of TGX-221, although there was limited steric tolerance for substituents on the pendant ring with the 2-position most favourable for substitution. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.03.073

文献信息

• [EN] INHIBITION OF PHOSPHOINOSITIDE 3-KINASE BETA<br/>[FR] INHIBITION DE LA PHOSPHOINOSITIDE 3-KINASE BETA
  申请人：KINACIA PTY LTD

  公开号：WO2004016607A1

  公开（公告）日：2004-02-26

  The present invention relates to selective inhibitors of phosphoinositide (PI) 3-kinase ß, use of the selective inhibitors in anti-thrombotic therapy, and a method for screening compounds useful for the new anti-thrombotic therapy by detecting selective inhibitory activity of PI 3-kinase ß of the compound. The invention also relates to novel compounds that are inhibitors of PI 3-kinase.

  本发明涉及磷酸肌醇（PI）3-激酶β的选择性抑制剂，以及这些选择性抑制剂在抗血栓治疗中的应用，以及通过检测化合物对PI 3-激酶β的选择性抑制活性来筛选对新型抗血栓治疗有用的化合物的方法。该发明还涉及作为PI 3-激酶抑制剂的新化合物。
• 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。
• Inhibition Of Phosphoinositide 3-Kinase Beta
  申请人：Jackson Shaun P.

  公开号：US20080319021A1

  公开（公告）日：2008-12-25

  The present invention relates to selective inhibitors of phosphoinositide (PI) 3-kinase β, use of the selective inhibitors in anti-thrombotic therapy, and a method for screening compounds useful for the new anti-thrombotic therapy by detecting selective inhibitory activity of PI 3-kinase β of the compound. The invention also relates to novel compounds that are inhibitors of PI 3-kinase.

  本发明涉及选择性磷脂酰肌醇（PI）3-激酶β的抑制剂，使用这些选择性抑制剂进行抗血栓治疗的方法，以及通过检测化合物的PI 3-激酶β的选择性抑制活性筛选有用于新抗血栓治疗的化合物的方法。该发明还涉及新型PI 3-激酶抑制剂化合物。
• 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。
• [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。