1,6-dimethyl-2-methoxymethyl-3-benzyloxypyridin-4(1H)-one | 734520-07-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,6-dimethyl-2-methoxymethyl-3-benzyloxypyridin-4(1H)-one
• 英文别名: 2-(Methoxymethyl)-1,6-dimethyl-3-phenylmethoxypyridin-4-one
• CAS: 734520-07-1
• 化学式: C₁₆H₁₉NO₃
• 分子量: 273.332
• InChiKey: KFXVDWITWDPTID-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  20
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  38.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,6-dimethyl-2-methoxymethyl-3-benzyloxypyridin-4(1H)-one 在 5%-palladium/activated carbon 盐酸 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 4.0h， 生成 1,6-Dimethyl-2-methoxymethyl-3-hydroxy-pyridin-4(1H)-one hydrochloride
  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
• 作为产物：
  描述：

  曲酸 在 盐酸 、 sodium hydroxide 、 氯化亚砜 、 四丁基硫酸氢铵 、 锌 作用下， 以 甲醇 、 乙醇 、 二氯甲烷 为溶剂， 反应 39.5h， 生成 1,6-dimethyl-2-methoxymethyl-3-benzyloxypyridin-4(1H)-one
  参考文献：
  名称：

  Design, Synthesis, and Evaluation of Novel 2-Substituted 3-Hydroxypyridin-4-ones:  Structure−Activity Investigation of Metalloenzyme Inhibition by Iron Chelators

  摘要：

  A range of novel 3-hydroxypyridin-4-ones with different R(2) substitutents has been synthesized for the investigation of the structure-activity relationship between the chemical nature of the ligand and the inhibitory activity of the iron-containing metalloenzyme 5-lipoxygenase. Results indicate that the molecular dimensions, together with the lipophilicity, have a critical impact on the ability of this class of chelator to inhibit 5-lipoxygenase. Hydrophilic ligands with a bulky R(2) substitutent tend to be weak inhibitors; thus 1,6-dimethyl-2-(4'-N-n-propylsuccinamido)methyl-3-hydroxypyridin-4(1H)-one (22b) which has the largest R(2) substitutent only caused 2% inhibition of the enzyme activity after 30 min incubation at 110 muM IBE (iron-binding equivalents), as compared with deferiprone which caused 40% inhibition of the enzyme activity, under the same conditions.

  DOI：

  10.1021/jm010817i

文献信息

• Novel orally active iron (III) chelators
  申请人：BTG International Limited.

  公开号：US20020068758A1

  公开（公告）日：2002-06-06

  A novel 3-hydroxypyridinone compound of formula I is provided 1 wherein R is hydrogen or a group that is removed by metabolism in vivo to provide the free hydroxy compound, R 1 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 C 1-6 alkoxy, C 6 -aryloxy or C 7-10 aralkoxy ether thereof, R 3 is selected from hydrogen and C 1-6 alkyl; and R 4 is selected from hydrogen, C 1-6 alkyl and a group as described for R 2 ; characterized in that R 2 is selected from groups (i) —CONH—R 5 (ii) —CH 2 NHCO—R 5 (iii) —SO 2 NH—R 5 (iv) —CH 2 NHSO 2 —R 5 (v) —CR 6 R 6 OR 7 (viii) —CONHCOR 5 wherein R 5 is selected from hydrogen and optionally hydroxy, alkoxy, or aralkoxy substituted C 1-13 alkyl, aryl and C 7-13 aralkyl, R 6 is independently selected from hydrogen, C 1-13 alkyl, aryl and C 7-13 aralkyl, and R 7 is selected from hydrogen, C 1-13 alkyl, aryl and C 7-13 aralkyl or a pharmaceutically acceptable salt of any such compound with the proviso that when R 7 is hydrogen, R 6 is not selected from aryl and with the proviso that the compound is not 1-ethyl-2-(1′-hydroxyethyl)-3-hydroxypyridin-4-one.

  提供了一种新的3-羟基吡啶酮化合物，其化学式为I，其中R为氢或代谢在体内提供自由羟基化合物的基团，R1为脂肪族烃基或被羟基基团或羧酸酯、磺酸酯或其C1-6烷氧基、C6-芳氧基或C7-10芳基烷氧基所取代的脂肪族烃基，R3选自氢和C1-6烷基；R4选自氢、C1-6烷基和如R2所述的基团，其中R2选自以下基团：(i) —CONH—R5(ii) —CH2NHCO—R5(iii) —SO2NH—R5(iv) —CH2NHSO2—R5(v) —CR6R6OR7(viii) —CONHCOR5，其中R5选自氢和可选的羟基、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，R6独立选自氢、C1-13烷基、芳基和C7-13芳基烷基，R7选自氢、C1-13烷基、芳基和C7-13芳基烷基，或任何这种化合物的药学上可接受的盐，但是当R7为氢时，R6不选自芳基，并且该化合物不是1-乙基-2-(1'-羟乙基)-3-羟基吡啶-4-酮。
• Design, Synthesis, and Evaluation of Novel 2-Substituted 3-Hydroxypyridin-4-ones:  Structure−Activity Investigation of Metalloenzyme Inhibition by Iron Chelators
  作者：Zu D. Liu、Reem Kayyali、Robert C. Hider、John B. Porter、Anthony E. Theobald

  DOI：10.1021/jm010817i

  日期：2002.1.1

  A range of novel 3-hydroxypyridin-4-ones with different R(2) substitutents has been synthesized for the investigation of the structure-activity relationship between the chemical nature of the ligand and the inhibitory activity of the iron-containing metalloenzyme 5-lipoxygenase. Results indicate that the molecular dimensions, together with the lipophilicity, have a critical impact on the ability of this class of chelator to inhibit 5-lipoxygenase. Hydrophilic ligands with a bulky R(2) substitutent tend to be weak inhibitors; thus 1,6-dimethyl-2-(4'-N-n-propylsuccinamido)methyl-3-hydroxypyridin-4(1H)-one (22b) which has the largest R(2) substitutent only caused 2% inhibition of the enzyme activity after 30 min incubation at 110 muM IBE (iron-binding equivalents), as compared with deferiprone which caused 40% inhibition of the enzyme activity, under the same conditions.
• 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。