2'-deoxy-2'-methylidene-5-methyluridine | 119410-90-1

• 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: 2'-deoxy-2'-methylidene-5-methyluridine
• 英文别名: 1-[(2r,4s,5r)-4-Hydroxy-5-(hydroxymethyl)-3-methylene-tetrahydrofuran-2-yl]-5-methyl-pyrimidine-2,4-dione；1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)-3-methylideneoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 119410-90-1
• 化学式: C₁₁H₁₄N₂O₅
• 分子量: 254.243
• InChiKey: SOZDVWZNTLEXIE-KHQFGBGNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  99.1
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3',5'-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-2'-deoxy-2'-methylidene-5-methyluridine 在 四丁基氟化铵 作用下， 以 四氢呋喃 为溶剂， 以85%的产率得到2'-deoxy-2'-methylidene-5-methyluridine
  参考文献：
  名称：

  核苷和核苷酸。97.合成新的广谱抗肿瘤核苷，2'-脱氧-2'-亚甲基胞苷（DMDC）及其衍生物。

  摘要：

  通过Wittig反应，由相应的2'-酮嘧啶核苷3和8合成了一种新型的抗肿瘤核苷2'-脱氧-2'-亚甲基胞苷（DMDC）。在反应过程中，我们发现中间体甜菜碱可以从过量的三苯基溴化pick中挑出质子形成2'-on盐5和10，并可以进一步转化为2'-脱氧-2'-亚甲基通过氢化钠处理得到核苷4和9。还从相应的5-取代的尿苷12a-f，h合成了各种5-取代的DMDC衍生物19a-e，h及其尿嘧啶同类物16a-h。其中，DMDC以及2'-脱氧-2'-亚甲基-5-氟胞苷（19a）对培养的鼠L1210细胞显示出有效的抗白血病活性。还检查了与1-β-D-阿拉伯呋喃糖基胞嘧啶胞嘧啶和5-氟尿嘧啶相比，DMDC和19a对培养的各种人类肿瘤细胞的活性。还描述了DMDC对L1210的体内抗肿瘤活性。

  DOI：

  10.1021/jm00106a049

文献信息

• Synthesis and anticancer and antiviral activities of various 2'- and 3'-methylidene-substituted nucleoside analogs and crystal structure of 2'-deoxy-2'-methylidenecytidine hydrochloride
  作者：Tai Shun Lin、Mei Zhen Luo、Mao Chin Liu、Regina H. Clarke-Katzenburg、Yung Chi Cheng、William H. Prusoff、William R. Mancini、George I. Birnbaum、Eric J. Gabe、Jerzy Giziewicz

  DOI：10.1021/jm00112a040

  日期：1991.8

  Various 2'- and 3'-methylidene-substituted nucleoside analogues have been synthesized and evaluated as potential anticancer and/or antiviral agents. Among these compounds, 2'-deoxy-2'-methylidene-5-fluorocytidine (22) and 2'-deoxy-2'-methylidenecytidine (23) not only demonstrated potent anticancer activity in culture against murine L1210 and P388 leukemias, Sarcoma 180, and human CCRF-CEM lymphoblastic

  已经合成了各种2'-和3'-亚甲基取代的核苷类似物，并将其评估为潜在的抗癌剂和/或抗病毒剂。在这些化合物中，2'-脱氧-2'-亚甲基-5-氟胞苷（22）和2'-脱氧-2'-亚甲基胞苷（23）不仅在培养中表现出对鼠L1210和P388白血病，肉瘤180的有效抗癌活性。 ，人CCRF-CEM淋巴母细胞性白血病，其ED50值分别为1.2和0.3 microM，0.6和0.4 microM，1.5和1.5 microM，0.05和0.03 microM，但在小鼠L1210白血病中也有活性。在所有测试的药物剂量水平（分别为25、50和75 mg / kg）中，化合物23没有毒性死亡，而化合物22在最高剂量水平下仅产生一个毒性死亡。相反，在同一项研究中，1-β-D-阿拉伯呋喃糖基胞嘧啶（ara-C）分别导致2 / 5、5 / 5和5/5毒性死亡。化合物22和23均显示出比ara-C更好的抗癌活性，产生更高的T
• Oligonucleotides having A-DNA form and B-DNA form conformational geometry
  申请人：——

  公开号：US20030096979A1

  公开（公告）日：2003-05-22

  Modified oligonucleotides containing both A-form conformation geometry and B-from conformation geometry nucleotides are disclosed. The B-form geometry allows the oligonucleotide to serve as substrates for RNase H when bound to a target nucleic acid strand. The A-form geometry imparts properties to the oligonucleotide that modulate binding affinity and nuclease resistance. By utilizing C2′ endo sugars or O4′ endo sugars, the B-form characteristics are imparted to a portion of the oligonucleotide. The A-form characteristics are imparted via use of either 2′-O-modified nucleotides that have 3′ endo geometries or use of end caps having particular nuclease stability or by use of both of these in conjunction with each other.

  修改的寡核苷酸同时包含A型构象几何和B型构象几何核苷酸。B型构象允许寡核苷酸在与靶核酸链结合时充当RNase H的底物。A型构象赋予寡核苷酸特定属性，调节结合亲和力和核酸酶抵抗性。通过利用C2′内醛糖或O4′内醛糖，将B型特性赋予寡核苷酸的一部分。通过使用具有3′内醛几何结构的2′-O修饰核苷酸或具有特定核酸酶稳定性的端盖，或者同时使用这两者来赋予A型特性。
• Human RNase H1 and oligonucleotide compositions thereof
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US20040102618A1

  公开（公告）日：2004-05-27

  The present invention provides oligonucleotides that can serve as substrates for human Type 2 RNase H. The present invention is also directed to methods of using these oligonucleotides in enhancing antisense oligonucleotide therapies.

  本发明提供了可以作为人类2型RNA酶H底物的寡核苷酸。本发明还涉及使用这些寡核苷酸增强反义寡核苷酸治疗的方法。
• Oligonucleotdies having A-DNA form and B-DNA form conformational geometry
  申请人：Manoharan Muthiah

  公开号：US20070123702A1

  公开（公告）日：2007-05-31

  Modified oligonucleotides containing both A-form conformation geometry and B-from conformation geometry nucleotides are disclosed. The B-form geometry allows the oligonucleotide to serve as substrates for RNase H when bound to a target nucleic acid strand. The A-form geometry imparts properties to the oligonucleotide that modulate binding affinity and nuclease resistance. By utilizing C2′ endo sugars or O4′ endo sugars, the B-form characteristics are imparted to a portion of the oligonucleotide. The A-form characteristics are imparted via use of either 2′-O-modified nucleotides that have 3′ endo geometries or use of end caps having particular nuclease stability or by use of both of these in conjunction with each other.

  本发明揭示了含有A形构象几何和B形构象几何核苷酸的修饰寡核苷酸。B形几何使寡核苷酸在与靶核酸链结合时可以作为RNase H的底物。A形几何赋予寡核苷酸特定的性质，可以调节结合亲和力和核酸酶抵抗性。通过利用C2′内糖或O4′内糖，将B形特征赋予寡核苷酸的一部分。通过使用具有3′内糖几何的2′-O修饰核苷酸或具有特定核酸酶稳定性的末端盖子或同时使用这两种方法，将A形特征赋予寡核苷酸。
• Human RNase H1 oligonucleotide compositions thereof
  申请人：Crooke T. Stanley

  公开号：US20070292875A1

  公开（公告）日：2007-12-20

  The present invention provides oligonucleotides that can serve as substrates for human Type 2 RNase H. The present invention is also directed to methods of using these oligonucleotides in enhancing antisense oligonucleotide therapies.

  本发明提供了可以作为人类2型RNase H底物的寡核苷酸。本发明还涉及使用这些寡核苷酸增强反义寡核苷酸治疗的方法。