N-(3-benzyloxy-6-methyl-pyran-4(1H)-one-2-carbonyl)-1,3-thiazolidine-2-thione | 216581-49-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃
• 英文名称: N-(3-benzyloxy-6-methyl-pyran-4(1H)-one-2-carbonyl)-1,3-thiazolidine-2-thione
• 英文别名: N-(3-benzyloxy-6-methylpyran-4(1H)-one-2-carbonyl)-1,3-thiazolidine-2-thione；3-(2-Carbonyl-3-benzyloxy-6-methyl-4(1H)-pyran-2-yl)-1,3-thiazolidine-2-thione；6-Methyl-3-phenylmethoxy-2-(2-sulfanylidene-1,3-thiazolidine-3-carbonyl)pyran-4-one
• CAS: 216581-49-6
• 化学式: C₁₇H₁₅NO₄S₂
• 分子量: 361.442
• InChiKey: OOHHAAXUPJEKBH-UHFFFAOYSA-N

物化性质

• 沸点：
  564.3±60.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  113
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  N-(3-benzyloxy-6-methyl-pyran-4(1H)-one-2-carbonyl)-1,3-thiazolidine-2-thione 生成 1,6-dimethyl-3-hydroxypyridin-4(1H)-one-2-carboxy-(N-isopropyl)-amide
  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：

  2-甲酰基-3-苄氧基-6-甲基-吡喃-4(1H)-酮 在 4-二甲氨基吡啶 、 sodium chlorite 、 氨基磺酸 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 25.0h， 生成 N-(3-benzyloxy-6-methyl-pyran-4(1H)-one-2-carbonyl)-1,3-thiazolidine-2-thione
  参考文献：
  名称：

  Synthesis of 2-amido-3-hydroxypyridin-4(1H)-ones: novel iron chelators with enhanced pFe3+ values

  摘要：

  The synthesis of a range of 2-amido-3-hydroxypyridin-4-ones as bidentate iron(III) chelators with potential for oral administration is described. The pKa values of the ligands together with the stability constants of their iron(III) complexes have been determined. Results indicate that the introduction of an amido substituent at the 2-position leads to an appreciable enhancement of the pFe(3+) values. 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. The optimal effect was observed with the N-methyl amido derivative 15b, which has an associated pFe(3+) value of 21.7, more than two orders of magnitude higher than that of deferiprone (1,2-dimethyl-3-hydroxypyridin-4-one) 1a (pFe(3+) = 19.4). Dose response studies suggest that chelators with high pFe(3+) values scavenge iron more effectively at lower doses when compared with simple dialkyl substituted hydroxypyridinones. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(00)00273-x

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。
• 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。
• Amido-3-hydroxypyridin-4-ones as Iron(III) Ligands
  作者：Sirivipa Piyamongkol、Yong M. Ma、Xiao L. Kong、Zu D. Liu、Mutlu D. Aytemir、Dick van der Helm、Robert C. Hider

  DOI：10.1002/chem.200902455

  日期：——

  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.
• PROCESSES FOR THE MANUFACTURING OF 3-HYDROXY-N,1,6-TRIALKYL-4-OXO-1,4-DIHYDROPYRIDINE-2-CARBOXAMIDE
  申请人：APOTEX INC.

  公开号：EP1440061B1

  公开（公告）日：2007-04-11
• US7893269B2
  申请人：——

  公开号：US7893269B2

  公开（公告）日：2011-02-22