5’-{4-[3-(ethoxycarbonyl)-7,8-dihydro-6,8,8-trimethyl-2-oxo-2H-pyrano[3,2-g]quinolin-9(6H)-yl]butanoyl}-2’,3’-O-[(1R)-4-ethoxy-1-methyl-4-oxobutylidene]-5-fluorouridine | 1590381-25-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: 5’-{4-[3-(ethoxycarbonyl)-7,8-dihydro-6,8,8-trimethyl-2-oxo-2H-pyrano[3,2-g]quinolin-9(6H)-yl]butanoyl}-2’,3’-O-[(1R)-4-ethoxy-1-methyl-4-oxobutylidene]-5-fluorouridine
• 英文别名: 5'-O-{4-[3-(ethoxycarbonyl)-6,8,8-trimethyl-2-oxo-7,8-dihydro-2H-pyrano[3,2-g]quinolin-9(6H)-yl]butanoyl}-2',3'-O-[(1R)-4-ethoxy-1-methyl-4-oxobutylidene]-5-fluorouridine；ethyl 9-[4-[[(2R,3aR,4R,6R,6aR)-2-(3-ethoxy-3-oxopropyl)-4-(5-fluoro-2,4-dioxopyrimidin-1-yl)-2-methyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy]-4-oxobutyl]-6,8,8-trimethyl-2-oxo-6,7-dihydropyrano[3,2-g]quinoline-3-carboxylate
• CAS: 1590381-25-1
• 化学式: C₃₈H₄₆FN₃O₁₃
• 分子量: 771.794
• InChiKey: MSHHHICPPXTYML-XXNQLAFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  55
• 可旋转键数：
  16
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  186
• 氢给体数：
  1
• 氢受体数：
  15

反应信息

• 作为产物：
  描述：

  AT425-酸 、 ethyl 3-[(2R,3aR,4R,6R,6aR)-4-(3,4-dihydro-5-fluoro-2,4-dioxopyrimidin-1(2H)-yl)-6-(hydroxymethyl)-2-methyltetrahydrofuro[3,4-d] [1,3]dioxol-2-yl]propanoate 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以100%的产率得到5’-{4-[3-(ethoxycarbonyl)-7,8-dihydro-6,8,8-trimethyl-2-oxo-2H-pyrano[3,2-g]quinolin-9(6H)-yl]butanoyl}-2’,3’-O-[(1R)-4-ethoxy-1-methyl-4-oxobutylidene]-5-fluorouridine
  参考文献：
  名称：

  5-氟尿苷核脂衍生物的合成及其对人 HT-29 结肠癌细胞的细胞抑制/细胞毒活性

  摘要：

  化学治疗剂的主要缺点之一是由于高疏水性，它们不能充分穿透细胞膜。因此，我们合成了一系列选定的 5-氟尿苷 (5-FUrd; 2a) 核脂衍生物，在 N(3) 和/或 2',3'-O-位（即 3a- 7a 和 3c)，并使用 HT-29 人结肠癌细胞测试它们的细胞抑制/细胞毒性活性，与例如 5-FU (1) 和 5-FUrd (2a) 进行比较。在与荧光染料 Atto 425 缀合后进行被测物质的掺入和细胞内定位。我们发现所有 5'-O 标记的 Atto 425 衍生物都被人类 HT-29 细胞掺入并积累在其细胞质中。此外，在 HT-29 人结肠癌细胞处理 24 小时后，1 或 2a (10, 20, 40, 或 80 μM）显示与（阴性）对照相比，存活率显着降低（分别为 14-23 或 33-45%）。有趣的是，衍生物 3a 和 3c（40 和 80 μM）导致显着（77-95 或 89-96%，分别）抑制人

  DOI：

  10.1002/cbdv.201300219

文献信息

• 5-Fluoruoracil Derivatives
  申请人：B. Braun Melsungen AG

  公开号：EP2712868A1

  公开（公告）日：2014-04-02

  The present invention relates to a compound represented by formula (I) wherein X is selected from the group of formulae (II) to (IV) wherein R1 is H or C1-C50 chain which may be branched or linear and which may be saturated or unsaturated and which may optionally be interrupted and/or substituted by one or more hetero atom(s) (Het1) and/or functional group(s)(G1); or R1 is a C3-C28 moiety which comprises at least one cyclic structure and which may be saturated or unsaturated and which may optionally be interrupted and/or substituted by one or more hetero atom(s) (Het1) and functional group(s)(G1); R2 is H; or R2 is a Mono-phosphate, Di-phosphate, Tri-phosphate or phosphoramidite moiety; or R2 is -Y-X or -Y-L-Y1- X; Y and Y1 are independently from each other a single bond or a functional connecting moiety, X is a colloid-active compound (CA) or a fluorescence marker (FA) or a polynucleotide moiety having up to 50 nucleotide residues, preferably 10 to 25 nucleotides, especially a polynucleotide having an antisense or antigen effect; L is a linker by means of which Y and X are covalently linked together; R3 and R4 represent independently from each other a C1-C28-alkyl moiety which may optionally be substituted or interrupted by one or more heteroatom(s) and/or functional group(s);or R3 and R4 form a ring having at least 5 members, preferably a ring having 5 to 8 carbon atoms and wherein the ring may be substituted or interrupted by one or more hetero atom(s) and/or functional group(s); or R3 and R4 represent independently from each other a C1-C28-alkyl moiety substituted with one or more moieties selected from the group -Y-X or -Y-L-Y1-X; or R3 and R4 represent independently from each other -Y-X or -Y-L-Y1- X; R5 and R6 represent independently from each other a C1-C28-alkyl moiety which may optionally be substituted or interrupted by one or more heteroatom(s) and/or functional group(s); or R5 and R6 represent independently from each other a C1-C28-alkyl moiety substituted with one or more moieties selected from the group -Y-X or -Y-L-Y1-X; or R5 and R6 form a ring having at least 5 members, preferably a ring having 5 to 18 carbon atoms and wherein the ring may be substituted or interrupted by one or more hetero atom(s) and/or functional group(s); and/or one or more moieties selected from the group -Y-X or -Y-L-Y1- X; R5 and R6 represent independently from each other -Y-X or -Y-L-Y1- X; R7 is a hydrogen atom or -O-R8; R8 is H or C1-C28 chain which may be branched or linear and which may be saturated or unsaturated and which may optionally be interrupted and/or substituted by one or more hetero atom(s) (Het1) and/or functional group(s)(G1); or R8 is -Y-X or -Y-L-Y1- X, with the proviso that R1 and R2 are not both H and/or with the proviso that the compound comprises at least two chains each of which having 4 or more carbon atoms.

  本发明涉及一种由以下公式（I）表示的化合物，其中X选自以下公式（II）至（IV）中的一种：其中R1为H或C1-C50链，可以是支链或直链，可以是饱和或不饱和，并且可能被一个或多个杂原子（Het1）和/或功能基团（G1）中断和/或取代；或R1为包含至少一个环结构的C3-C28基团，可以是饱和或不饱和，并且可能被一个或多个杂原子（Het1）和功能基团（G1）中断和/或取代；R2为H；或R2为单磷酸酯、双磷酸酯、三磷酸酯或磷酰胺基团；或R2为-Y-X或-Y-L-Y1-X；Y和Y1分别独立地为单键或功能连接基团；X为胶体活性化合物（CA）或荧光标记物（FA）或具有最多50个核苷酸残基的多核苷酸基团，优选为10至25个核苷酸，特别是具有反义或抗原效应的多核苷酸；L为连接剂，用于将Y和X共价连接在一起；R3和R4分别独立地表示可以选择性地被一个或多个杂原子和/或功能基团取代或中断的C1-C28烷基基团；或R3和R4形成具有至少5个成员的环，优选为具有5至8个碳原子的环，并且该环可以被一个或多个杂原子和/或功能基团取代或中断；或R3和R4分别独立地表示用一个或多个从-Y-X或-Y-L-Y1-X中选择的基团取代的C1-C28烷基基团；或R3和R4分别独立地表示-Y-X或-Y-L-Y1-X；R5和R6分别独立地表示可以选择性地被一个或多个杂原子和/或功能基团取代或中断的C1-C28烷基基团；或R5和R6分别独立地表示用一个或多个从-Y-X或-Y-L-Y1-X中选择的基团取代的C1-C28烷基基团；或R5和R6形成具有至少5个成员的环，优选为具有5至18个碳原子的环，并且该环可以被一个或多个杂原子和/或功能基团取代或中断；和/或一个或多个从-Y-X或-Y-L-Y1-X中选择的基团；R5和R6分别独立地表示-Y-X或-Y-L-Y1-X；R7为氢原子或-O-R8；R8为H或C1-C28链，可以是支链或直链，可以是饱和或不饱和，并且可能被一个或多个杂原子（Het1）和/或功能基团（G1）中断和/或取代；或R8为-Y-X或-Y-L-Y1-X，但R1和R2不能同时为H，且化合物至少包含两条每条至少有4个或更多碳原子的链。
• 5-Fluorouracil Derivatives
  申请人：B. Braun Melsungen AG

  公开号：US20150291649A1

  公开（公告）日：2015-10-15

  The present invention relates to 5-fluorouracil derivatives represented by formula (i), pharmaceutical compositions comprising said derivative and their use in the treatment of cancer as well as a process for preparing the 5-fluorouracil derivative represented by formula (I).

  本发明涉及由式（i）表示的5-氟尿嘧啶衍生物，包括该衍生物的制药组合物及其在癌症治疗中的应用，以及制备由式（I）表示的5-氟尿嘧啶衍生物的过程。
• US9902752B2
  申请人：——

  公开号：US9902752B2

  公开（公告）日：2018-02-27