3-hydroxypyridin-4(1H)-one-2-carboxamide | 760164-44-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 3-hydroxypyridin-4(1H)-one-2-carboxamide
• 英文别名: 2-Pyridinecarboxamide, 3,4-dihydroxy-；3-hydroxy-4-oxo-1H-pyridine-2-carboxamide
• CAS: 760164-44-1
• 化学式: C₆H₆N₂O₃
• mdl: MFCD18816461
• 分子量: 154.125
• InChiKey: PHRPQQJEKRXVNO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  92.4
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-hydroxypyridin-4(1H)-one-2-carboxamide 在 盐酸 作用下， 以 水 为溶剂， 生成 3-hydroxypyridin-4(1H)-one-2-carboxyamide hydrochloride
  参考文献：
  名称：

  Amido-3-hydroxypyridin-4-ones as Iron(III) Ligands

  摘要：

  AbstractThe synthesis and physicochemical properties of a range of 2‐ and 6‐amido‐3‐hydroxypyridin‐4‐ones are described. All the amido‐substituted 3‐hydroxypyridin‐4‐ones have lower pKa values than 1,2‐dimethyl‐3‐hydroxypyridin‐4‐one (deferiprone). This is due to the inductive effect of the amido group. Furthermore, the pKa values of the 3‐hydroxy group in 1‐nonsubstituted pyridinones are dramatically lower than those of the corresponding 1‐alkyl analogues, indicating that a strong hydrogen bond exists between the 2‐amido function and the 3‐oxygen anion, which stabilises the anion. As a result of the decreased competition with protons, the pFe3+ values of this group of molecules are higher than that of deferiprone. The distribution coefficients of these molecules are also increased despite the lack of a hydrophobic 1‐alkyl substituent and this is ascribed to the intramolecular hydrogen bond. X‐ray diffraction studies confirm the existence of the intramolecular hydrogen bond.

  DOI：

  10.1002/chem.200902455
• 作为产物：
  描述：

  3,4-dibenzyloxypyridine-2-carboxamide 在 palladium on activated carbon 、 氢气 作用下， 以 甲醇 为溶剂， 反应 3.0h， 生成 3-hydroxypyridin-4(1H)-one-2-carboxamide
  参考文献：
  名称：

  Amido-3-hydroxypyridin-4-ones as Iron(III) Ligands

  摘要：

  AbstractThe synthesis and physicochemical properties of a range of 2‐ and 6‐amido‐3‐hydroxypyridin‐4‐ones are described. All the amido‐substituted 3‐hydroxypyridin‐4‐ones have lower pKa values than 1,2‐dimethyl‐3‐hydroxypyridin‐4‐one (deferiprone). This is due to the inductive effect of the amido group. Furthermore, the pKa values of the 3‐hydroxy group in 1‐nonsubstituted pyridinones are dramatically lower than those of the corresponding 1‐alkyl analogues, indicating that a strong hydrogen bond exists between the 2‐amido function and the 3‐oxygen anion, which stabilises the anion. As a result of the decreased competition with protons, the pFe3+ values of this group of molecules are higher than that of deferiprone. The distribution coefficients of these molecules are also increased despite the lack of a hydrophobic 1‐alkyl substituent and this is ascribed to the intramolecular hydrogen bond. X‐ray diffraction studies confirm the existence of the intramolecular hydrogen bond.

  DOI：

  10.1002/chem.200902455

文献信息

• N-benzyl-3,4-dihyroxypyridine-2-carboxamide and n-benzyl-2,3-dihydroxypyridine-4- carboxamide compounds useful as hiv integrase inhibitors
  申请人：Jones Philip

  公开号：US20070155744A1

  公开（公告）日：2007-07-05

  N-Benzyl-dihydroxypyridine carboxamide compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the dihydroxypyridine carboxamides are of Formula (I) wherein Q is Formula (II) or Formula (III); T is Formula (IV); and R 1 , R 2 , X 1 ,X 2 ,X 3 , and Y 1 are defined herein. The 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.

  N-苄基二羟基吡啶羧酰胺化合物是HIV整合酶的抑制剂，也是HIV复制的抑制剂。在一种实施例中，二羟基吡啶羧酰胺为式（I）中的化合物，其中Q为式（II）或式（III）；T为式（IV）；R1、R2、X1、X2、X3和Y1在此处定义。这些化合物对预防和治疗HIV感染以及预防、延迟发病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抗击HIV感染和艾滋病。这些化合物及其盐可作为药物组成部分，可选择地与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。
• [EN] HIV INTEGRASE INHIBITORS<br/>[FR] INHIBITEURS DE L'INTÉGRASE DU VIH
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2005087766A1

  公开（公告）日：2005-09-22

  Pyridopyrazine- and pyrimidopyrazine-dione compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the dihydroxypyridine carboxamides are of Formula (I); wherein G, Q, bond a, R5, R6 and R7 are defined herein. The 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.

  吡啶吡嘧啶酮和嘧啶吡嘧啶二酮化合物是HIV整合酶的抑制剂，也是HIV复制的抑制剂。在一个实施例中，二羟基吡啶羧酰胺属于式（I）的化合物；其中G，Q，键a，R5，R6和R7在此处有定义。这些化合物对预防和治疗HIV感染以及预防、延迟发病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中的成分使用，可选地与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。
• Cycloalkyl derivatives of 3-hydroxy-4-pyridinones field of the invention
  申请人：Tam Fat Tim

  公开号：US20070082904A1

  公开（公告）日：2007-04-12

  The present invention provides an cycloalkyl derivative of 3-hydroxy-4-pyridinone which is useful for the chelation of metal ions such as iron. Its preparation and use is described. In particular, the invention concerns the removal of iron in chemical and biological systems including chelating agents having the formula (I); wherein R 1 is X with the proviso that R 2 is y; or R 1 is T with the proviso that R 2 is W; or R 1 is X with the proviso that R 2 R 5 N when taken together form a heterocyclic ring selected from piperidinyl, morpholinyl, pyrrolidinyl or piperazinyl, wherein the group piperidinyl, morphoninyl, pyrrolidinyl or piperazinyl is either unsubstituted or substituted with one to three C 1 to C 6 alkyl groups. X is C 3 -C 6 cycloalkyl; Y is selected from the group consisting of C, to C 6 cycloalkyl; C 1 to C 6 alkyl, and C 1 to C 6 alkyl monosubstituted with a C 3 -C 6 cycloalkyl; T is C 1 to C 6 alkyl; W is C 3 -C 6 cycloalkyl; R 3 is selected from the group consisting of hydrogen and C 1 to C 6 alkyl; R 4 is selected from the group consisting of hydrogen and C 1 to C 6 alkyl; R 5 is selected from the group consisting of hydrogen and C 1 to C 6 alkyl; and its pharmaceutically acceptable salt thereof. Pharmaceutical compositions of such compounds are useful in the removal of excess body iron from patients with iron overload diseases.

  本发明提供了3-羟基-4-吡啶酮的环烷基衍生物，可用于螯合金属离子，如铁离子。描述了其制备和用途。特别是，本发明涉及化学和生物系统中铁的去除，包括具有式（I）的螯合剂，其中R1为X，但R2为y；或R1为T，但R2为W；或R1为X，但R2R5N在一起形成从哌啶基，吗啉基，吡咯烷基或哌嗪基中选择的杂环环，其中哌啶基，吗啉基，吡咯烷基或哌嗪基的基团是未取代的或用1至3个C1至C6烷基基团取代的。X为C3-C6环烷基；Y选自由C到C6环烷基；C1到C6烷基和C1到C6烷基单取代的C3-C6环烷基；T为C1到C6烷基；W为C3-C6环烷基；R3选自氢和C1到C6烷基的群；R4选自氢和C1到C6烷基的群；R5选自氢和C1到C6烷基的群；以及其药学上可接受的盐。这些化合物的制药组合物可用于治疗铁过载病患者的体内多余铁的去除。
• Process For The Manufacture Of 3-Hydroxy-N-Alkyl-1-Cycloalkyl-6-Alkyl-4-Oxo-1,4-Dihydropyridine-2-Carboxamide And Its Related Analogues
  申请人：Tam Fat Tim

  公开号：US20080096886A1

  公开（公告）日：2008-04-24

  The present invention relates to a novel process for the preparation of 1-alkyl or 1-cycloalkyl derivatives of 3-hydroxy-4-oxo-1,4-dihydropyridine-2-carboxamide of formula I. The process includes reacting an amine R 2 NH 2 with a compound of formula II in a solution of metal hydroxide in water to give a compound of formula III. Subsequent reaction of the compound of formula III with an acid chloride formation reagent in an inert solvent gives compounds of formula I. The acid chloride formation reagent is selected from oxalyl chloride and dimethylformamide, dimethylchloromethylene-ammonium chloride and thionyl chloride and dimethylformamide. If desired, a compound of formula I where R 5 is hydrogen may be formed when an intermediate substituent is used wherein R 5 is an alcohol protective group removable by catalytic hydrogenation.

  本发明涉及一种新型方法，用于制备式I的1-烷基或1-环烷基的3-羟基-4-氧代-1,4-二氢吡啶-2-羧酰胺衍生物。该方法包括将胺R2NH2与式II的化合物在水中的金属氢氧化物溶液中反应，以得到式III的化合物。随后，在惰性溶剂中使用酸氯化物形成试剂与式III的化合物反应，得到式I的化合物。酸氯化物形成试剂选自草酰氯和二甲基甲酰胺、二甲基氯甲基胺盐酸盐和亚磺酰氯和二甲基甲酰胺。如果需要，当使用中间体取代基时，可以形成式I的化合物，其中R5为氢，R5是通过催化氢化可去除的醇保护基。
• Hiv integrase inhibitors
  申请人：Jones Philip

  公开号：US20070161639A1

  公开（公告）日：2007-07-12

  Pyridopyrazine- and pyrimidopyrazine-dione compounds are inhibitors of HIV integrase and inhibitors of HIV replication. In one embodiment, the dihydroxypyridine carboxamides are of Formula (I); wherein G, Q, bond a, R 5 , R 6 and R 7 are defined herein. The 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.

  吡啶并吡嗪和嘧啶并吡嗪二酮化合物是HIV整合酶的抑制剂和HIV复制的抑制剂。在一种实施例中，二羟基吡啶羧酰胺为式（I）；其中G、Q、键a、R5、R6和R7的定义如本文所述。这些化合物在预防和治疗HIV感染以及预防、延迟发病和治疗艾滋病方面非常有用。这些化合物可以作为化合物本身或作为药物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成部分，可与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。