1-[(2R,3R,4R,5S)-4-(azidomethyl)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-phenoxycarbothioyloxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione | 816452-29-6

• 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-[(2R,3R,4R,5S)-4-(azidomethyl)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-phenoxycarbothioyloxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
• CAS: 816452-29-6
• 化学式: C₂₄H₃₃N₅O₆SSi
• 分子量: 547.707
• InChiKey: BTOHOBAKPISRKO-ANTGDGSKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.44
• 重原子数：
  37
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  133
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  1-[(2R,3R,4R,5S)-4-(azidomethyl)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-phenoxycarbothioyloxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione 在 偶氮二异丁腈 、 四丁基氟化铵 、 三正丁基氢锡 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 6.0h， 生成 1,3-bis[(3R)-(3'-deoxythymidin-3'-yl)methyl]urea
  参考文献：
  名称：

  发现双环胸苷类似物作为结核分枝杆菌胸苷单磷酸激酶的选择性和高亲和力抑制剂。

  摘要：

  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。

  DOI：

  10.1021/jm040847w
• 作为产物：
  描述：

  1,2-O-isopropylidene-5-O-(tert-butyl)dimethylsilyl-α-D-xylofuranoside 在 四氢呋喃 、 吡啶 、 chromium(VI) oxide 、 4-二甲氨基吡啶 、 sodium hydroxide 、 叠氮化锂 、 C₄F₉SO₃K 、 硼烷 、 氨 、 双氧水 、 乙酸酐 、 sodium hydride 、 silver nitrate 、 溶剂黄146 、 六甲基二硅氮烷 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 109.5h， 生成 1-[(2R,3R,4R,5S)-4-(azidomethyl)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-3-phenoxycarbothioyloxyoxolan-2-yl]-5-methylpyrimidine-2,4-dione
  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

文献信息

• 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.
• 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。