8-oxo-4,8-dihydro-2-phenyl-5-[(3'-benzoyloxy)propyl]-4H-pyridino[3,2-d]-m-dioxin | 216580-53-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-oxo-4,8-dihydro-2-phenyl-5-[(3'-benzoyloxy)propyl]-4H-pyridino[3,2-d]-m-dioxin
• 英文别名: 3-(8-oxo-2-phenyl-4H-[1,3]dioxino[5,4-b]pyridin-5-yl)propyl benzoate
• CAS: 216580-53-9
• 化学式: C₂₃H₂₁NO₅
• 分子量: 391.423
• InChiKey: WOIUHLVNVUWGAY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  65.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  8-oxo-4,8-dihydro-2-phenyl-5-[(3'-benzoyloxy)propyl]-4H-pyridino[3,2-d]-m-dioxin 在 palladium on activated charcoal 盐酸 、 氢气 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 以85%的产率得到1-[(3'-benzoyloxy)propyl]-2-hydroxymethyl-3-hydroxypyridin-4(1H)-one hydrochloride
  参考文献：
  名称：

  Synthesis, Physicochemical Characterization, and Biological Evaluation of 2-(1‘-Hydroxyalkyl)-3-hydroxypyridin-4-ones:  Novel Iron Chelators with Enhanced pFe³⁺ Values

  摘要：

  The synthesis of a range of 2-(1'-hydroxyalkyl)-3-hydroxypyridin-4-ones as bidentate iron(III) chelators with potential for oral administration is described. The pK(a) values of the ligands and the stability constants of their iron(III) complexes have been determined. Results indicate that the introduction of a 1'-hydroxyalkyl group at the 2-position leads to a significant improvement in the pFe(3+) values. Such an effect was found to be greater with the hydroxyethyl substituent than with the hydroxymethyl substituent, particularly in the cases of 1-ethyl-2-(1'-hydroxyethyl)-3-hydroxypyridin-4-one (pFe(3+) = 21.4) and 1,6-dimethyl-2-(1'-hydroxyethyl)-3-hydroxypyridin-4-one (pFe(3+) = 21.5) where an enhancement on pFe(3+) values in the region of two orders of magnitude is observed, Bs compared with Deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one) (pFe(3+) = 19.4). The ability of these novel 3-hydroxypyridin-4-ones to facilitate the iron excretion in bile was investigated using a [Fe-59]ferritin-loaded rat model. Chelators and prodrug chelators possessing high pFe(3+) values show great promise in their ability to remove iron under in vivo conditions.

  DOI：

  10.1021/jm991080o
• 作为产物：
  描述：

  8-oxo-4,8-dihydro-2-phenyl-4H-pyrano[3,2-d]-m-dioxin 在 sodium hydroxide 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 3.0h， 生成 8-oxo-4,8-dihydro-2-phenyl-5-[(3'-benzoyloxy)propyl]-4H-pyridino[3,2-d]-m-dioxin
  参考文献：
  名称：

  Orally active iron (III) chelators

  摘要：

  提供一种化合物，其为一种新颖的3-羟基吡啶-4-酮化合物，其化学式为I，其中R为氢或在体内代谢中被去除以提供游离羟基化合物的基团，R1为脂肪烃基团或被羟基或羧酸酯、磺酸酯或其C1-6烷氧基、C6芳基氧基或C7-10芳基烷氧基所取代的脂肪烃基团，R3从氢和C1-6烷基中选择；R4从氢、C1-6烷基和如R2所述的基团中选择；其中R2从以下基团中选择：—CONH—R5 (i)—CH2NHCO—R5 (ii)—SO2NH—R5 (iii)—CH2NHSO2—R5 (iv)—CR6R6OR7 (v)—CONHCOR5 (viii) 其中R5从氢和可选的羟基、烷氧基或芳基烷氧基取代的C1-13烷基、芳基和C7-13芳基烷基中选择，R6独立选择自氢、C1-13烷基、芳基和C7-13芳基烷基，R7从氢、C1-13烷基、芳基和C7-13芳基烷基中选择，或任何这种化合物的药用盐；但是当R7为氢时，R6不选择自芳基，并且化合物不是1-乙基-2-(1'-羟乙基)-3-羟基吡啶-4-酮。

  公开号：

  US06335353B1

文献信息

• Orally active iron (III) chelators
  申请人：BTG International Limited

  公开号：US06335353B1

  公开（公告）日：2002-01-01

  A novel 3-hydroxypyridin-4-one compound of formula I is provided wherein R is hydrogen or a group that is removed by metabolism in vivo to provide the free hydroxy compound, R1 is an aliphatic hydrocarbon group or an aliphatic hydrocarbon group substituted by a hydroxy group or a carboxylic acid ester, sulpho acid ester or a C1-6 alkoxy, C6-aryloxy or C7-10aralkoxy ether thereof, R3 is selected from hydrogen and C1-6alkyl; and R4 is selected from hydrogen, C1-6alkyl and a group as described for R2; characterised in that R2 is selected from groups —CONH—R5  (i) —CH2NHCO—R5  (ii) —SO2NH—R5  (iii) —CH2NHSO2—R5  (iv) —CR6R6OR7  (v) —CONHCOR5  (viii)  wherein R5 is selected from hydrogen and optionally hydroxy, alkoxy, or aralkoxy substituted C1-13 alkyl, aryl and C71-13 aralkyl, R6 is independently selected from hydrogen, C1-13 alkyl, aryl and C7-13 aralkyl, and R7 is selected from hydrogen, C1-13 alkyl, aryl and C7-13 aralkyl or a pharmaceutically acceptable salt of any such compound with the proviso that when R7 is hydrogen, R6 is not selected from aryl and with the proviso that the compound is not 1-ethyl-2-(1′-hydroxyethyl)-3-hydroxypyridin-4-one.

  提供一种化合物，其为一种新颖的3-羟基吡啶-4-酮化合物，其化学式为I，其中R为氢或在体内代谢中被去除以提供游离羟基化合物的基团，R1为脂肪烃基团或被羟基或羧酸酯、磺酸酯或其C1-6烷氧基、C6芳基氧基或C7-10芳基烷氧基所取代的脂肪烃基团，R3从氢和C1-6烷基中选择；R4从氢、C1-6烷基和如R2所述的基团中选择；其中R2从以下基团中选择：—CONH—R5 (i)—CH2NHCO—R5 (ii)—SO2NH—R5 (iii)—CH2NHSO2—R5 (iv)—CR6R6OR7 (v)—CONHCOR5 (viii) 其中R5从氢和可选的羟基、烷氧基或芳基烷氧基取代的C1-13烷基、芳基和C7-13芳基烷基中选择，R6独立选择自氢、C1-13烷基、芳基和C7-13芳基烷基，R7从氢、C1-13烷基、芳基和C7-13芳基烷基中选择，或任何这种化合物的药用盐；但是当R7为氢时，R6不选择自芳基，并且化合物不是1-乙基-2-(1'-羟乙基)-3-羟基吡啶-4-酮。
• Synthesis, Physicochemical Characterization, and Biological Evaluation of 2-(1‘-Hydroxyalkyl)-3-hydroxypyridin-4-ones:  Novel Iron Chelators with Enhanced pFe³⁺ Values
  作者：Zu D. Liu、Hicham H. Khodr、Ding Y. Liu、Shu L. Lu、Robert C. Hider

  DOI：10.1021/jm991080o

  日期：1999.11.1

  The synthesis of a range of 2-(1'-hydroxyalkyl)-3-hydroxypyridin-4-ones as bidentate iron(III) chelators with potential for oral administration is described. The pK(a) values of the ligands and the stability constants of their iron(III) complexes have been determined. Results indicate that the introduction of a 1'-hydroxyalkyl group at the 2-position leads to a significant improvement in the pFe(3+) values. Such an effect was found to be greater with the hydroxyethyl substituent than with the hydroxymethyl substituent, particularly in the cases of 1-ethyl-2-(1'-hydroxyethyl)-3-hydroxypyridin-4-one (pFe(3+) = 21.4) and 1,6-dimethyl-2-(1'-hydroxyethyl)-3-hydroxypyridin-4-one (pFe(3+) = 21.5) where an enhancement on pFe(3+) values in the region of two orders of magnitude is observed, Bs compared with Deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one) (pFe(3+) = 19.4). The ability of these novel 3-hydroxypyridin-4-ones to facilitate the iron excretion in bile was investigated using a [Fe-59]ferritin-loaded rat model. Chelators and prodrug chelators possessing high pFe(3+) values show great promise in their ability to remove iron under in vivo conditions.