5'-O-{[bis(1-methylethyl)amino](2-cyanoethoxy)phosphino}-5-fluoro-2’,3’-O-(1-propylbutylidene)-3-[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrien-1-yl]uridine | 1581758-42-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: 5'-O-{[bis(1-methylethyl)amino](2-cyanoethoxy)phosphino}-5-fluoro-2’,3’-O-(1-propylbutylidene)-3-[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrien-1-yl]uridine
• 英文别名: 2-cyanoethyl-(((3aR,4R,6R,6aR)-6-(5-fluoro-2,4-dioxo-3-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dipropyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl) diisopropylphosphoramidite；2-cyanoethyl [(3aR,4R,6R,6aR)-6-{5-fluoro-2,4-dioxo-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl]-3,4-dihydropyrimidin-1(2H)-yl}-2,2-dipropyltetrahydrofuro[3,4-d][1,3]dioxol-4-yl]methyl bis(1-methylethyl)phosphoramidoite；2-Cyanoethyl (((3aR,4R,6R,6aR)-6-(5-fluoro-2,4-dioxo-3-((2E,6E)-3,7,11-trimethyldodeca-2,6,10-trien-1-yl)-3,4-dihydropyrimidin-1(2H)-yl)-2,2-dipropyl-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methyl) diisopropylphosphoramidite；3-[[(3aR,4R,6R,6aR)-4-[5-fluoro-2,4-dioxo-3-[(2E,6E)-3,7,11-trimethyldodeca-2,6,10-trienyl]pyrimidin-1-yl]-2,2-dipropyl-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-6-yl]methoxy-[di(propan-2-yl)amino]phosphanyl]oxypropanenitrile
• CAS: 1581758-42-0
• 化学式: C₄₀H₆₄FN₄O₇P
• 分子量: 762.943
• InChiKey: RROAAZPXKKFHIO-VVRTVIMYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.84
• 重原子数：
  53.0
• 可旋转键数：
  22.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.72
• 拓扑面积：
  117.18
• 氢给体数：
  0.0
• 氢受体数：
  11.0

反应信息

• 作为产物：
  描述：

  4-庚酮 在 potassium carbonate 、 N,N-二异丙基乙胺 、 原甲酸三乙酯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.42h， 生成 5'-O-{[bis(1-methylethyl)amino](2-cyanoethoxy)phosphino}-5-fluoro-2’,3’-O-(1-propylbutylidene)-3-[(2E,6E)-3,7,11-trimethyl-2,6,10-dodecatrien-1-yl]uridine
  参考文献：
  名称：

  抑制癌的 5-氟尿苷的核脂：合成、寡核苷酸的粘附和人工脂质双层的掺入

  摘要：

  5-氟尿苷 (1a) 通过与法呢基溴 (4) 直接烷基化转化为其 N(3)-法呢基化核萜衍生物 8。抑癌剂 1a 与丙酮、庚烷-4-one、十九烷-10-one 或十六烷-16-one 反应得到 2',3'-O-缩酮 2a-2d。然后化合物 2b 首先被法呢基化 (→5) 然后亚磷酸化得到亚磷酰胺 6。缩酮 2c 直接被 5'-亚磷酸化而不对碱进行法呢基化得到亚磷酰胺 7。此外，最近制备的环状 2',3' -O-缩酮 11 被 5'-亚磷酸酯化以产生亚磷酰胺 12。2',3'-O-异亚丙基衍生物 2a 被证明太不稳定而无法转化为亚磷酰胺。1a 的所有新衍生物均通过 NMR 和 UV 光谱和 ESI 质谱以及元素分析明确表征。亚磷酰胺前体的亲脂性通过它们在 RP-18 HPLC 中的保留时间和计算的 log P 值来表征。亚磷酰胺 6、7 和 12 示例性地用于制备在 5'-(n-1) 位置（即

  DOI：

  10.1002/cbdv.201300127

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。