5’-O-(mesyl)zidovudine | 87190-86-1

• 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: 5’-O-(mesyl)zidovudine
• 英文别名: [(2S,3S,5R)-3-azido-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl methanesulfonate
• CAS: 87190-86-1
• 化学式: C₁₁H₁₅N₅O₆S
• 分子量: 345.336
• InChiKey: QXGSBTXYDBLAOA-DJLDLDEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  125
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  5’-O-(mesyl)zidovudine 在 palladium on activated charcoal potassium fluoride 、 氢气 作用下， 以 乙醇 、 乙二醇 为溶剂， 25.0~135.0 ℃ 、344.73 kPa 条件下， 反应 4.5h， 生成 3'-amino-3'-deoxy-5'-fluorothymidine
  参考文献：
  名称：

  Synthesis and biological activity of various 3'-azido and 3'-amino analogs of 5-substituted pyrimidine deoxyribonucleosides

  摘要：

  Various new 5-substituted 3'-azido- and 3'-amino derivatives of 2'-deoxyuridine and 2'-deoxycytidine have been synthesized and biologically evaluated. Among these compounds, 3'-amino-2',3'-dideoxy-5-fluorouridine (3), 3'-amino-2',3'-dideoxycytidine (7a), and 3'-amino-2',3'-dideoxy-5-fluorocytidine (7c) were found to be the most active against murine L1210 and sarcoma 180 neoplastic cells in vitro, with an ED50 of 15 and 1 microM, 0.7 and 4 microM, and 10 and 1 microM, respectively. The 3'-azido derivatives, 2 and 6c, were less active in comparison with their 3'-amino counterparts. In addition, the 5-fluoro-3'-amino nucleosides, 3 and 7c, were tested against L1210 leukemia bearing CDF1 mice. Our preliminary findings indicate that compound 7c (6 X 200 mg/kg) was as active as the positive control, 5-fluorouracil (6 X 20 mg/kg), yielding a T/C X 100 of 146 and 129, respectively. However, 3 was found to be inactive in this experiment.

  DOI：

  10.1021/jm00366a006
• 作为产物：
  描述：

  齐多夫定 、 甲基磺酰氯 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以92 %的产率得到5’-O-(mesyl)zidovudine
  参考文献：
  名称：

  新型 5'-arylchalcogenyl-3'-N-(E)-feruloyl-3', 5'-dideoxy-amino-thymidine (AFAT) 衍生物的合成、抗氧化和抗肿瘤活性

  摘要：

  公开了一类新的 5'-芳基硫族基-3'- N- ( E )-feruloyl-3'-amino-3'-deoxythymidine (AFAT) 衍生物的合成。通过采用温和条件的酰胺化反应以良好的收率获得化合物。评估了针对膀胱癌细胞 T24 的抗肿瘤活性和新衍生物的抗氧化作用。获得的结果表明与商业标准或前体结构单元相比，TBARS 产生和 DPPH 清除活性有显着抑制作用。此外，碲 AFAT 衍生物显示出显着的抗增殖活性。体内_研究表明，用 AFAT 衍生物治疗的小鼠组在治疗 1 周后保持正常的健康状况，并且在体内生化测定中未观察到肾或肝毒性。计算机评估证实了实验结果，并证明了这些化合物作为多靶点药物的突出能力。

  DOI：

  10.1039/d2nj03487e

文献信息

• Evaluation of the effect of synthetic compounds derived from azidothymidine on MDA-MB-231 type breast cancer cells
  作者：Adriely Maria Oliveira Rocha、Fernanda Severo Sabedra Sousa、Victoria Mascarenhas Borba、Taiana S. Munchen、Julliano Guerin Leal、Oscar Endrigo Dorneles Rodrigues、Mariana G. Fronza、Lucielli Savegnago、Tiago Collares、Fabiana Kömmling Seixas

  DOI：10.1016/j.bmcl.2020.127365

  日期：2020.9

  cycle arrest in the S phase. Besides, predicted absorption, distribution, metabolization, excretion and toxicity analysis suggest that the compounds possess a good pharmacokinetic profile and possibly less toxicity when compared to conventional AZT. These compounds containing tellurium in their formulation are potential therapeutic agents for breast cancer.

  本研究旨在研究含碲（Te）的AZT衍生物对人乳腺癌细胞系的影响以及细胞死亡的潜在机制。AZT及其衍生物（7m和7r的抑制作用）。通过MTT测定（在24和48小时时间点分别为6.25、12.5、25、50和100μM）测定），同时通过流式细胞术研究细胞凋亡的诱导和细胞周期阶段。MTT分析表明，在浓度为12.5μM的条件下，AZT衍生物可降低细胞增殖速率，而商用AZT则显示出较低的抗肿瘤潜力。在流式细胞仪分析中，我们证明了AZT衍生物在所测试的浓度下不会诱导细胞凋亡，并促进了S期的细胞周期停滞。此外，预测的吸收，分布，代谢，排泄和毒性分析表明，与常规AZT相比，该化合物具有良好的药代动力学特征，且毒性可能更低。这些在制剂中含有碲的化合物是潜在的乳腺癌治疗剂。
• Antiviral Effect of 5′-Arylchalcogeno-3-aminothymidine Derivatives in SARS-CoV-2 Infection
  作者：Amanda Resende Tucci、Raquel Mello da Rosa、Alice Santos Rosa、Otávio Augusto Chaves、Vivian Neuza Santos Ferreira、Thamara Kelcya Fonseca Oliveira、Daniel Dias Coutinho Souza、Nathalia Roberto Resende Borba、Luciano Dornelles、Nayra Salazar Rocha、João Candido Pilar Mayer、João B. Teixeira da Rocha、Oscar Endrigo D. Rodrigues、Milene Dias Miranda

  DOI：10.3390/molecules28186696

  日期：——

  discovery of novel potential anti-coronavirus compounds. Here, the antiviral activity of selenium and tellurium containing AZT derivatives in human type II pneumocytes cell model (Calu-3) and monkey kidney cells (Vero E6) infected with SARS-CoV-2, and their toxic effects on these cells, was evaluated. Cell viability analysis revealed that organoselenium (R3a-R3e) showed lower cytotoxicity than organotellurium

  齐多夫定（ZDV 或叠氮胸苷，AZT）抑制 SARS-CoV-2 的 RNA 依赖性 RNA 聚合酶（RdRp）以及硫属原子可以增加 AZT 的生物活性并降低毒性，这一认识指导我们寻找新的药物潜在的抗冠状病毒化合物。本研究评估了含 AZT 衍生物的硒和碲在感染 SARS-CoV-2 的人 II 型肺细胞模型 (Calu-3) 和猴肾细胞 (Vero E6) 中的抗病毒活性及其对这些细胞的毒性作用。细胞活力分析显示，有机硒 (R3a-R3e) 的细胞毒性低于有机碲 (R3f、R3n-R3q)，CC50 ≥ 100 µM。R3b 和 R3e 在抑制两种细胞模型中的病毒复制方面尤其值得注意，并表现出更好的选择性指数。在 Vero E6 中，R3b 和 R3e 的 EC50 值分别为 2.97 ± 0.62 µM 和 1.99 ± 0.42 µM，而在 Calu-3 中，浓度分别为 3.82 ± 1
• New Organochalcogen Multitarget Drug: Synthesis and Antioxidant and Antitumoral Activities of Chalcogenozidovudine Derivatives
  作者：Diego de Souza、Douglas O. C. Mariano、Fernanda Nedel、Eduarda Schultze、Vinícius F. Campos、Fabiana Seixas、Rafael S. da Silva、Taiana S. Munchen、Vinicius Ilha、Luciano Dornelles、Antonio L. Braga、João B. T. Rocha、Tiago Collares、Oscar E. D. Rodrigues

  DOI：10.1021/jm5015296

  日期：2015.4.23

  In this article we present the synthesis, characterization, and in vitro biological and biochemical activities Of new chalcogenozidovudine derivatives as antioxidant (inhibition of TBARS in brain membranes and thiol peroxidase-like activity) as well as antitumoral agents in bladder carcinoma 5637. A prominent response was obtained for the selected chalcogenonucleosides, showing effective antioxidant and antitumoral activities.
• Synthesis and biological activity of various 3'-azido and 3'-amino analogs of 5-substituted pyrimidine deoxyribonucleosides
  作者：Tai Shun Lin、You Song Gao、William R. Mancini

  DOI：10.1021/jm00366a006

  日期：1983.12

  Various new 5-substituted 3'-azido- and 3'-amino derivatives of 2'-deoxyuridine and 2'-deoxycytidine have been synthesized and biologically evaluated. Among these compounds, 3'-amino-2',3'-dideoxy-5-fluorouridine (3), 3'-amino-2',3'-dideoxycytidine (7a), and 3'-amino-2',3'-dideoxy-5-fluorocytidine (7c) were found to be the most active against murine L1210 and sarcoma 180 neoplastic cells in vitro, with an ED50 of 15 and 1 microM, 0.7 and 4 microM, and 10 and 1 microM, respectively. The 3'-azido derivatives, 2 and 6c, were less active in comparison with their 3'-amino counterparts. In addition, the 5-fluoro-3'-amino nucleosides, 3 and 7c, were tested against L1210 leukemia bearing CDF1 mice. Our preliminary findings indicate that compound 7c (6 X 200 mg/kg) was as active as the positive control, 5-fluorouracil (6 X 20 mg/kg), yielding a T/C X 100 of 146 and 129, respectively. However, 3 was found to be inactive in this experiment.
• Synthesis, antioxidant and antitumoral activity of new 5′-arylchalcogenyl-3′-<i>N</i>-(<i>E</i>)-feruloyl-3′, 5′-dideoxy-amino-thymidine (AFAT) derivatives
  作者：Julliano G. Leal、Bruna Candia Piccoli、Cláudia Sirlene Oliveira、Fernanda D’Avila da Silva、Folorunsho Bright Omage、João Batista Teixeira da Rocha、Mariana Souza Sonego、Natália Vieira Segatto、Fabiana Kommling Seixas、Tiago Veiras Collares、Rafael Santos da Silva、Joelma Menegazzi Sarturi、Luciano Dornelles、Maria Amparo F. Faustino、Oscar E. D. Rodrigues

  DOI：10.1039/d2nj03487e

  日期：——

  The synthesis of a new class of 5′-arylchalcogenyl-3′-N-(E)-feruloyl-3′-amino-3′-deoxythymidine (AFAT) derivatives is disclosed. The compounds were obtained in good yields by an amidation reaction employing soft conditions. Both antitumoral activity against bladder carcinoma cells T24 and the antioxidant effect of the new derivatives were assessed. The results obtained demonstrated a notable inhibition

  公开了一类新的 5'-芳基硫族基-3'- N- ( E )-feruloyl-3'-amino-3'-deoxythymidine (AFAT) 衍生物的合成。通过采用温和条件的酰胺化反应以良好的收率获得化合物。评估了针对膀胱癌细胞 T24 的抗肿瘤活性和新衍生物的抗氧化作用。获得的结果表明与商业标准或前体结构单元相比，TBARS 产生和 DPPH 清除活性有显着抑制作用。此外，碲 AFAT 衍生物显示出显着的抗增殖活性。体内_研究表明，用 AFAT 衍生物治疗的小鼠组在治疗 1 周后保持正常的健康状况，并且在体内生化测定中未观察到肾或肝毒性。计算机评估证实了实验结果，并证明了这些化合物作为多靶点药物的突出能力。