1-<3-C-(azidomethyl)-3-deoxy-α-D-erythro-pentofuranosyl>thymine | 146035-79-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘧啶核苷
• 英文名称: 1-<3-C-(azidomethyl)-3-deoxy-α-D-erythro-pentofuranosyl>thymine
• 英文别名: 1-[3-C-(azidomethyl)-3-deoxy-α-D-erythro-pentofuranosyl]thymine；1-(4-Azidomethyl-3-hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-5-methyl-1H-pyrimidine-2,4-dione；1-[(2R,3R,4S,5S)-4-(azidomethyl)-3-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 146035-79-2
• 化学式: C₁₁H₁₅N₅O₅
• 分子量: 297.271
• InChiKey: JSXXEEOHRDWOFK-FDDDBJFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.7
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-<3-C-(azidomethyl)-3-deoxy-α-D-erythro-pentofuranosyl>thymine 在 吡啶 、 sodium hydroxide 、 silver nitrate 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 27.25h， 生成 1-<3-C-(azidomethyl)-3-deoxy-β-D-threo-pentofuranosyl>thymine
  参考文献：
  名称：

  Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides

  摘要：

  Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells and HSV-1, HSV-2, and HIV-1 in culture. Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 muM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-1 (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine.

  DOI：

  10.1021/jm00055a006
• 作为产物：
  描述：

  O,O-二(三甲基甲硅烷基)胸苷 在 吡啶 、 sodium azide 、 ammonium cerium(IV) nitrate 、 三氟甲磺酸三甲基硅酯 、 氨 、 水 、 三氯化硼 作用下， 以 甲醇 、 二氯甲烷 、 1,2-二氯乙烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 22.83h， 生成 1-<3-C-(azidomethyl)-3-deoxy-α-D-erythro-pentofuranosyl>thymine
  参考文献：
  名称：

  3'-C支链取代的核苷和核苷酸作为结核分枝杆菌胸苷单磷酸激酶的有效抑制剂。

  摘要：

  结核分枝杆菌（TMPKmt）的胸苷单磷酸激酶（TMPK）代表了一种阻断细菌DNA合成的有吸引力的靶标。为了找到TMPKmt的高亲和力抑制剂，通过在胸苷单磷酸（dTMP）支架的3'-位置引入各种取代基来探索酶在3'-位置的空腔。从一个关键的中间体（23）合成了2'-脱氧核糖（3-6）和核糖系列（7，8）中的各种3'-C支链取代的核苷酸。2'-脱氧类似物被证明是TMPKmt的有效抑制剂：3'-CH（2）NH（2）（4），3'-CH（2）N（3）（3）和3'-CH（2 F（5）个核苷酸在该系列中表现出最高亲和力，K（i）值分别为10.5、12和15 microM。这些结果表明，TMPKmt可耐受在3'-位引入空间上要求的取代基。核糖类似物经历了显着的亲和力降低，这可能是由于Tyr103在2'位置附近的空间位阻。尽管5'-O-磷酸化的化合物对酶具有更高的亲和力，但亲本核苷通常以相同的数量级显示出对

  DOI：

  10.1021/jm021108n

文献信息

• Discovery of Bicyclic Thymidine Analogues as Selective and High-Affinity Inhibitors of <i>Mycobacterium tuberculosis</i> Thymidine Monophosphate Kinase
  作者：Veerle Vanheusden、Hélène Munier-Lehmann、Matheus Froeyen、Roger Busson、Jef Rozenski、Piet Herdewijn、Serge Van Calenbergh

  DOI：10.1021/jm040847w

  日期：2004.12.1

  Thymidine monophosphate kinase of Mycobacterium tuberculosis (TMPKmt) represents an attractive target for selectively blocking bacterial DNA synthesis. Hereby, we report on the discovery of a novel class of bicyclic nucleosides (10 and 11) and one dinucleoside (12), belonging to the most selective inhibitors of TMPKmt discovered so far.

  结核分枝杆菌（TMPKmt）的胸苷单磷酸激酶代表了选择性阻断细菌DNA合成的诱人靶标。据此，我们报道了一种新型的双环核苷（10和11）和一个二核苷（12）的发现，它们属于迄今为止发现的最具选择性的TMPKmt抑制剂。
• Syntheses and biological evaluations of 3'-deoxy-3'-C-branched-chain-substituted nucleosides
  作者：Tai Shun Lin、Ju Liang Zhu、Ginger E. Dutschman、Yung Chi Cheng、William H. Prusoff

  DOI：10.1021/jm00055a006

  日期：1993.2

  Various 3'-deoxy-3'-C-(hydroxymethyl)-, 3'-deoxy-3'-C-(fluoromethyl)-, 3'-deoxy-3'-C-(azidomethyl)-, and 3'-deoxy-3'-C-(aminomethyl)-substituted nucleosides (total 12 compounds) have been synthesized and evaluated against L1210, P388, S-180, and CCRF-CEM cells and HSV-1, HSV-2, and HIV-1 in culture. Only 3'-deoxy-3'-C-(hydroxymethyl)thymidine (36) was found to show significant anticancer activity against L1210, P388, S-180, and CCRF-CEM cells with ED50 values of 50, 5, 10, and 1 muM, respectively. None of these compounds demonstrated significant antiviral activity against HSV-1, HSV-2, or HIV-1. These compounds were also evaluated against thymidine kinases derived from HSV-1 (strain KOS), HSV-2 (strain 333), and mammalian (K562) cells. The thymidine kinase (HSV-1 strain KOS) was inhibited significantly by both 3'-deoxy-3'-C-(hydroxymethyl)- and 3'-deoxy-3'-C-(fluoromethyl)thymidine.
• 3‘-<i>C</i>-Branched-Chain-Substituted Nucleosides and Nucleotides as Potent Inhibitors of <i>Mycobacterium </i><i>t</i><i>uberculosis </i>Thymidine Monophosphate Kinase
  作者：Veerle Vanheusden、Hélène Munier-Lehmann、Matheus Froeyen、Laurence Dugué、Arne Heyerick、Denis De Keukeleire、Sylvie Pochet、Roger Busson、Piet Herdewijn、Serge Van Calenbergh

  DOI：10.1021/jm021108n

  日期：2003.8.1

  3'-position was explored via the introduction of various substituents at the 3'-position of the thymidine monophosphate (dTMP) scaffold. Various 3'-C-branched chain substituted nucleotides in the 2'-deoxyribo (3-6) and ribo series (7, 8) were synthesized from one key intermediate (23). 2'-Deoxy analogues proved to be potent inhibitors of TMPKmt: 3'-CH(2)NH(2) (4), 3'-CH(2)N(3) (3), and 3'-CH(2)F (5) nucleotides

  结核分枝杆菌（TMPKmt）的胸苷单磷酸激酶（TMPK）代表了一种阻断细菌DNA合成的有吸引力的靶标。为了找到TMPKmt的高亲和力抑制剂，通过在胸苷单磷酸（dTMP）支架的3'-位置引入各种取代基来探索酶在3'-位置的空腔。从一个关键的中间体（23）合成了2'-脱氧核糖（3-6）和核糖系列（7，8）中的各种3'-C支链取代的核苷酸。2'-脱氧类似物被证明是TMPKmt的有效抑制剂：3'-CH（2）NH（2）（4），3'-CH（2）N（3）（3）和3'-CH（2 F（5）个核苷酸在该系列中表现出最高亲和力，K（i）值分别为10.5、12和15 microM。这些结果表明，TMPKmt可耐受在3'-位引入空间上要求的取代基。核糖类似物经历了显着的亲和力降低，这可能是由于Tyr103在2'位置附近的空间位阻。尽管5'-O-磷酸化的化合物对酶具有更高的亲和力，但亲本核苷通常以相同的数量级显示出对