3-羟基-4-氧代-6,7,8,9-四氢-4H-吡啶并[1,2-A]嘧啶-2-羧酸甲酯 | 724445-24-3

• 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: 3-羟基-4-氧代-6,7,8,9-四氢-4H-吡啶并[1,2-A]嘧啶-2-羧酸甲酯
• 英文名称: methyl 3-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxylate
• 英文别名: methyl-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxylate；methyl 3-hydroxy-4-oxo-4,6,7,8-tetrahydropyrido[1,2-a]pyrimidine-2-carboxylate；methyl 3-hydroxy-4-oxo-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidine-2-carboxylate
• CAS: 724445-24-3
• 化学式: C₁₀H₁₂N₂O₄
• 分子量: 224.216
• InChiKey: XPNODRGEKBEUOO-UHFFFAOYSA-N

物化性质

• 沸点：
  352.8±52.0 °C(Predicted)
• 密度：
  1.49±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  79.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-羟基-4-氧代-6,7,8,9-四氢-4H-吡啶并[1,2-A]嘧啶-2-羧酸甲酯 在 4-二甲氨基吡啶 、 N-溴代丁二酰亚胺(NBS) 、 三乙胺 、 过氧化苯甲酰 作用下， 以 四氢呋喃 、 四氯化碳 为溶剂， 反应 3.0h， 生成 methyl 3-(benzoyloxy)-9-bromo-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxylate
  参考文献：
  名称：

  The synthesis of tetrahydropyridopyrimidones as a new scaffold for HIV-1 integrase inhibitors

  摘要：

  An efficient synthesis of methyl 9-amino-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxylate as a late stage intermediate for a new class of HIV-1 integrase inhibitors is described. After construction of the bicyclic core scaffold, a stereoselective introduction of the chiral amino group in the 9-position is achieved. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2007.07.043
• 作为产物：
  描述：

  5-氯戊腈 在 palladium on activated charcoal 盐酸 、 氢气 、 sodium hydride 、 三乙胺 、 sodium iodide 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 、 邻二甲苯 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.0h， 生成 3-羟基-4-氧代-6,7,8,9-四氢-4H-吡啶并[1,2-A]嘧啶-2-羧酸甲酯
  参考文献：
  名称：

  The synthesis of tetrahydropyridopyrimidones as a new scaffold for HIV-1 integrase inhibitors

  摘要：

  An efficient synthesis of methyl 9-amino-3-hydroxy-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxylate as a late stage intermediate for a new class of HIV-1 integrase inhibitors is described. After construction of the bicyclic core scaffold, a stereoselective introduction of the chiral amino group in the 9-position is achieved. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2007.07.043

文献信息

• [EN] TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDINES AND RELATED COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS<br/>[FR] TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDINES ET COMPOSES CONNEXES CONVENANT COMME INHIBITEURS DE L'INTEGRASE DU VIH
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2004058756A1

  公开（公告）日：2004-07-15

  Tetrahydro-4H-pyrido[1,2-a]pyrimidines and related compounds of Formula (A): are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein n is an integer equal to zero, 1, 2 or 3, and R1, R3, R4, R12, R14, R16, R30, R32, R34 and R36 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

  Tetrahydro-4H-pyrido[1,2-a]pyrimidines及其相关化合物的化学式（A）如下：被描述为HIV整合酶的抑制剂和HIV复制的抑制剂，其中n是一个等于零、1、2或3的整数，而R1、R3、R4、R12、R14、R16、R30、R32、R34和R36在此处被定义。这些化合物对预防和治疗HIV感染以及预防、延缓艾滋病发作和治疗艾滋病具有用处。这些化合物可作为化合物本身或作为药学上可接受的盐的形式用于对抗HIV感染和艾滋病。这些化合物及其盐可作为药物组合物的成分，可选择性地与其他抗病毒药物、免疫调节剂、抗生素或疫苗结合使用。
• [EN] PYRIMIDINONE COMPOUNDS AND METHODS FOR PREVENTING AND TREATING INFLUENZA<br/>[FR] COMPOSÉS DE PYRIMIDINONE ET MÉTHODES DE PRÉVENTION ET DE TRAITEMENT DE LA GRIPPE
  申请人：ST JUDE CHILDRENS RES HOSPITAL

  公开号：WO2012151567A1

  公开（公告）日：2012-11-08

  In one aspect, the invention relates to novel, broad-spectrum anti-viral, pyrimidinone compounds, methods of use, compositions and kits useful in treating and/or preventing influenza. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

  在一个方面，该发明涉及新颖的、广谱抗病毒的嘧啶酮化合物，以及用于治疗和/或预防流感的方法、组合物和工具包。本摘要旨在作为在特定领域进行搜索的扫描工具，并不意味着对本发明的限制。
• Design and Synthesis of Bicyclic Pyrimidinones as Potent and Orally Bioavailable HIV-1 Integrase Inhibitors
  作者：Ester Muraglia、Olaf Kinzel、Cristina Gardelli、Benedetta Crescenzi、Monica Donghi、Marco Ferrara、Emanuela Nizi、Federica Orvieto、Giovanna Pescatore、Ralph Laufer、Odalys Gonzalez-Paz、Annalise Di Marco、Fabrizio Fiore、Edith Monteagudo、Massimiliano Fonsi、Peter J. Felock、Michael Rowley、Vincenzo Summa

  DOI：10.1021/jm701164t

  日期：2008.2.1

  HIV integrase is one of the three enzymes encoded by HIV genome and is essential for viral replication, but integrase inhibitors as marketed drugs have just very recently started to emerge. In this study, we show the evolution from the N-methylpyrimidinone structure to bicyclic pyrimidinones. Introduction of a suitably substituted amino moiety modulated the physical-chemical properties of the molecules

  HIV整合酶是HIV基因组编码的三种酶之一，对于病毒复制至关重要，但是作为上市药物的整合酶抑制剂是最近才开始出现的。在这项研究中，我们显示了从N-甲基嘧啶酮结构向双环嘧啶酮的演变。引入适当取代的氨基部分可调节分子的物理化学性质，并在抑制HIV-1感染在细胞培养中扩散方面赋予纳米摩尔活性。广泛的SAR研究导致了磺酰胺（R）-22b，它以7 nM的IC50抑制了链转移，并以44 nM的CIC95抑制了MT4细胞中的HIV感染，
• HIV INTEGRASE INHIBITORS
  申请人：Summa Vincenzo

  公开号：US20090221571A1

  公开（公告）日：2009-09-03

  Pyridopyrimidine carboxamide compounds of Formula I are inhibitors of HIV integrase and inhibitors of HIV replication: wherein R 1 , R 2 , R 3 , R 4 , R 5 and R 6 are defined herein. The compounds are useful for the prophylaxis or treatment of infection by HIV and the prophylaxis, treatment, or delay in the onset of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

  公式I的吡啶基嘧啶羧酰胺化合物是HIV整合酶的抑制剂，也是HIV复制的抑制剂：其中R1、R2、R3、R4、R5和R6在此被定义。这些化合物可用于预防或治疗HIV感染，以及预防、治疗或延缓艾滋病的发作。这些化合物可作为药物本身或作为药学上可接受的盐形式用于对抗HIV感染和艾滋病。这些化合物及其盐可用作药物组合物的成分，可选地与其他抗病毒药物、免疫调节剂、抗生素或疫苗结合使用。
• [EN] TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDINES AND RELATED COMPOUNDS USEFUL AS HIV INTEGRASE INHIBITORS<br/>[FR] TETRAHYDRO-4H-PYRIDO[1,2-A]PYRIMIDINES ET COMPOSES ASSOCIES UTILISES EN TANT QU'INHIBITEURS DE L'INTEGRASE DU VIH
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2004058757A1

  公开（公告）日：2004-07-15

  Tetrahydro-4H-pyrido[1,2-a]pyrimidines and related compounds of Formula (I): are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein n is an integer equal to zero, 1 or 2, and R1, R3, R4, R12 and R14 are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines.

  描述了公式（I）中的四氢-4H-吡啶并[1,2-a]嘧啶及其相关化合物作为HIV整合酶抑制剂和HIV复制抑制剂，其中n是等于零、1或2的整数，R1、R3、R4、R12和R14在此定义。这些化合物对于预防和治疗HIV感染以及预防、延缓发病和治疗艾滋病非常有用。这些化合物可作为化合物本身或药学上可接受的盐的形式用于对抗HIV感染和艾滋病。这些化合物及其盐可作为成分用于制药组合物中，可选择与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。