5-fluoro-2'-deoxyuridine 3',5'-cyclic monophosphate | 36519-08-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 5-fluoro-2'-deoxyuridine 3',5'-cyclic monophosphate
• 英文别名: 5-fluoro-cdUMP；1-[(4aR,6R,7aS)-2-hydroxy-2-oxo-4a,6,7,7a-tetrahydro-4H-furo[3,2-d][1,3,2]dioxaphosphinin-6-yl]-5-fluoropyrimidine-2,4-dione
• CAS: 36519-08-1
• 化学式: C₉H₁₀FN₂O₇P
• 分子量: 308.16
• InChiKey: CEEUOYKVNIFZLL-RRKCRQDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.7
• 重原子数：
  20
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  114
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5-fluoro-2'-deoxyuridine 3',5'-cyclic monophosphate 、 碘甲烷 在 Amberlite IR-120 、 银 作用下， 生成 5-fluoro-2'-deoxyuridine 3',5'-cyclic monophosphate P-OMe 、 5-fluoro-2'-deoxyuridine 3',5'-cyclic monophosphate P-OMe
  参考文献：
  名称：

  有效合成某些5-取代的2'-脱氧尿苷3'，5'-环单磷酸对烷基（芳烷基）酯。带有轴向甲氧基的5-IODO-2'-脱氧尿苷3'，5'-环单磷酸对甲基酯的晶体和分子结构

  摘要：

  由母体环状单磷酸酯的银盐和烷基（芳烷基）碘化物的银盐制备了一些5-烷基-和5-卤代-2'-脱氧尿苷3'，5'-环状单磷酸PO-烷基（芳烷基）酯。非对映体磷酸三酯已通过光谱法表征。已经确定了具有轴向甲氧基的5-碘-2'-脱氧尿苷3'，5'-环单磷酸PO-甲酯的晶体和分子结构。与文献先前的权利要求相反，我们无法从cAMP银盐与烷基碘的反应中获得所需的三酯。

  DOI：

  10.1016/0040-4020(84)80024-1
• 作为产物：
  描述：

  5-fluoro-2'-deoxyuridine 5'-monophosphate N,N'-dicyclohexyl-4-morpholinecarboxamidine salt 在 N,N'-二环己基碳二亚胺 作用下， 以 吡啶 为溶剂， 反应 1.5h， 生成 5-fluoro-2'-deoxyuridine 3',5'-cyclic monophosphate
  参考文献：
  名称：

  5-卤代和5-（三氟甲基）-2'-脱氧尿苷3'，5'-环一磷酸和中性三酯的合成及其抗肿瘤和抗病毒特性。

  摘要：

  标题二酯（11-15；卤素取代基F，Cl，Br，I）是通过DCC诱导的前体5'-单磷酸环化或2'-脱氧尿苷3'，5'-环单磷酸的直接卤化制备的。将细胞系统（L1210和Raji / 0）中11-15的抗肿瘤活性与相应核苷和5'-单磷酸酯的抗肿瘤活性进行了比较。因此，5-F-和5-CF3-2'-脱氧尿苷被证明是高活性衍生物[L1210的ID50值（微克/ mL），分别为0.002和0.06]，而5'-单磷酸酯显示出可比的效能。相应的3'，5'-环一磷酸二酯的效力降低了20-30倍，但仍具有高度的细胞抑制作用。包括11-15在内的所有衍生物对于胸苷激酶缺陷（TK-）L1210和Raji细胞的ID50值均大大提高。3'，5' -环二酯（11-15）显然不是TK细胞中核苷5'-单磷酸的有效前药来源。他们还被证明是L1210胸苷酸合成酶抑制剂的效率比5'-单磷酸酯低100-2000倍。5-取代的2'

  DOI：

  10.1021/jm00157a022

文献信息

• Pharmaceutical compositions for high-capacity targeted delivery
  申请人：Wake Forest University Health Sciences

  公开号：US10105446B2

  公开（公告）日：2018-10-23

  Provided herein are aptamers and pharmaceutical compositions comprising the same. In some embodiments, the aptamer selectively binds a protein of interest such as an extracellular receptor protein of interest (e.g., a cancer cell extracellular receptor protein, which may be differentially expressed in some embodiments). In some embodiments, the aptamer is directly linked by covalent bonding (e.g., via a geminal diamine linkage) to from 2 to 10 toxin compounds. Also provided herein is a method of selecting an aptamer that specifically binds to a protein expressed by a cell of interest, wherein in some embodiments the aptamer comprises at least one binding site for one or more active compounds. In some embodiments, primer regions flanking the variable region of the aptamers in the pool contains from 1 to 10 mismatches with respect to said forward or reverse primer.

  本文提供的是适配体和包含适配体的药物组合物。在一些实施方案中，适配体选择性地结合感兴趣的蛋白，如感兴趣的细胞外受体蛋白（如癌细胞细胞外受体蛋白，在一些实施方案中可能是差异表达的）。在某些实施方案中，合体通过共价键（例如，通过基端二胺连接）与 2 至 10 种毒素化合物直接连接。本文还提供了一种选择与相关细胞表达的蛋白质特异性结合的适配体的方法，其中在一些实施方案中，适配体包括至少一个与一种或多种活性化合物结合的位点。在一些实施方案中，池中适配体的可变区侧翼引物区相对于所述正向或反向引物包含 1 至 10 个错配。
• MULTIVALENT APTAMER COMPLEXES
  申请人：Gmeiner William H.

  公开号：US20100261781A1

  公开（公告）日：2010-10-14

  A compound of the formula A-B-C, is provided, wherein: A is a first nucleic acid that specifically binds to an extracellular surface protein expressed by a cell of interest, B is an alkyl linker; and C is a second nucleic acid that hybridizes to a complementary nucleic acid. In some embodiments, the first nucleic acid is an aptamer. In some embodiments, the nucleic acid comprises an active compound, particularly cytotoxic nucleotides such as poly-FdUMP. Compositions and methods of using such compounds for treating and/or detecting cancer are also described.
• Cytotoxic Nucleotides for Targeted Therapeutics
  申请人：Gmeiner William H.

  公开号：US20110213135A1

  公开（公告）日：2011-09-01

  The present invention provides a method of generating a nucleic acid, which specifically binds to an extracellular surface protein expressed by a cell of interest, and which nucleic acid comprises a compound of interest to be delivered to the cell of interest.
• METHOD OF TREATING ACUTE MYELOGENOUS LEUKEMIA
  申请人：Gmeiner William H.

  公开号：US20130041018A1

  公开（公告）日：2013-02-14

  A method of treating acute myelogenous leukemia (AML) in a subject in need thereof is carried out by administering the subject an active compound in an amount effective to treat the leukemia. The active compound comprises FdUMP[10] or a pharmaceutically acceptable salt thereof.
• PHARMACEUTICAL COMPOSITIONS FOR HIGH-CAPACITY TARGETED DELIVERY
  申请人：Wake Forest University Health Sciences

  公开号：US20150094359A1

  公开（公告）日：2015-04-02

  Provided herein are aptamers and pharmaceutical compositions comprising the same. In some embodiments, the aptamer selectively binds a protein of interest such as an extracellular receptor protein of interest (e.g., a cancer cell extracellular receptor protein, which may be differentially expressed in some embodiments). In some embodiments, the aptamer is directly linked by covalent bonding (e.g., via a geminal diamine linkage) to from 2 to 10 toxin compounds. Also provided herein is a method of selecting an aptamer that specifically binds to a protein expressed by a cell of interest, wherein in some embodiments the aptamer comprises at least one binding site for one or more active compounds. In some embodiments, primer regions flanking the variable region of the aptamers in the pool contains from 1 to 10 mismatches with respect to said forward or reverse primer.