9-溴-2-羟基-7-甲基-4H-吡啶并[1,2-a]嘧啶-4-酮 | 663619-90-7

• 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
• 中文名称: 9-溴-2-羟基-7-甲基-4H-吡啶并[1,2-a]嘧啶-4-酮
• 中文别名: 9-溴-2-羟基-7-甲基-4H-吡啶并[1,2-A]嘧啶-4-酮
• 英文名称: 9-bromo-2-hydroxy-7-methyl-4H-pyrido[1,2-a]pyrimidin-4-one
• 英文别名: 9-bromo-2-hydroxy-7-methylpyrido [1,2-a]pyrimidin-4-one；9-Bromo-2-hydroxy-7-methylpyrido[1,2-a]pyrimidin-4-one
• CAS: 663619-90-7
• 化学式: C₉H₇BrN₂O₂
• 分子量: 255.071
• InChiKey: GDFHXJXNYYMCMC-UHFFFAOYSA-N

物化性质

• 沸点：
  377.1±52.0 °C(Predicted)
• 密度：
  1.79

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  52.9
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  9-溴-2-羟基-7-甲基-4H-吡啶并[1,2-a]嘧啶-4-酮 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride sodium carbonate 、 三氯氧磷 作用下， 以 四氢呋喃 为溶剂， 反应 43.0h， 生成 MCA49
  参考文献：
  名称：

  Isoform-specific phosphoinositide 3-kinase inhibitors from an arylmorpholine scaffold

  摘要：

  Phosphoinositide 3-kinases (PI3-Ks) are an ubiquitous class of signaling enzymes that regulate diverse cellular processes including growth, differentiation, and motility. Physiological roles of PI3-Ks have traditionally been assigned using two pharmacological inhibitors, LY294002 and wortmannin. Although these compounds are broadly specific for the PI3-K family, they show little selectivity among family members, and the development of isoform-specific inhibitors of these enzymes has been long anticipated. Herein, we prepare compounds from two classes of arylmorpholine PI3-K inhibitors and characterize their specificity against a comprehensive panel of targets within the PI3-K family. We identify multiplex inhibitors that potently inhibit distinct subsets of PI3-K isoforms, including the first selective inhibitor of p110beta/p110delta (IC50 p110beta = 0.13 muM, p110delta = 0.63 muM). We also identify trends that suggest certain PI3-K isoforms may be more sensitive to potent inhibition by arylmorpholines, thereby guiding future drug design based on this pharmacophore. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.022
• 作为产物：
  描述：

  2-氨基-5-甲基吡啶 在 溴 、 sodium acetate 、 溶剂黄146 作用下， 以 丙酮 为溶剂， 反应 2.0h， 生成 9-溴-2-羟基-7-甲基-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] ALLOSTERIC CHROMENONE INHIBITORS OF PHOSPHOINOSITIDE 3-KINASE (PI3K) FOR THE TREATMENT OF DISEASES ASSOCIATED WITH P13K MODULATION<br/>[FR] INHIBITEURS CHROMÉNONE ALLOSTÉRIQUES DE LA PHOSPHOINOSITIDE 3-KINASE (PI3K) POUR LE TRAITEMENT DE MALADIES ASSOCIÉES À LA MODULATION DE PI3K
  申请人：PETRA PHARMA CORP

  公开号：WO2021202964A1

  公开（公告）日：2021-10-07

  The disclosure relates to compounds of Formula (I) as allosteric chromenone inhibitors of phosphoinositide 3-kinase (PI3K) useful in the treatment of diseases or disorders associated with PI3K modulation, Formula (I), or a prodrug, solvate, enantiomer, stereoisomer, tautomer, or pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8, R9, W, X, Y, s, and Ring A are as described herein.

  该披露涉及到式(I)的化合物，作为磷脂酰肌醇3-激酶（PI3K）的变构色酮抑制剂，在与PI3K调节相关的疾病或紊乱的治疗中有用，式(I)，或其前药、溶剂化合物、对映体、立体异构体、互变异构体或其药学上可接受的盐，其中R1、R2、R3、R4、R5、R6、R7、R8、R9、W、X、Y、s和环A如本文所述。
• [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。
• Synthesis of New TGX-221 Analogs
  作者：Chunjing Liu、Benyi Li、Lester Mitscher

  DOI：10.5560/znb.2014-4081

  日期：2014.7.1

  TGX-221 is a potent phosphoinositide 3-kinase (PI3K)β inhibitor that has great therapeutic potential to treat prostate cancer. Chemical modification of TGX-221 at positions 2 and 9 was made. Five new TGX-221 analogs with different heterocyclic substituents of morpholine, 1-methylpiperazine, aniline, and thiazole-2-amine at positions 2 and 9 were synthesized. Parallel synthetic methods were employed in S_N2 replacement reactions at positions 2 and 9 of TGX-221.

  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。
• 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。
• [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。