2′-deoxy-2′-fluoro-2-iodoadenosine | 157762-25-9

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: 2′-deoxy-2′-fluoro-2-iodoadenosine
• 英文别名: 2-iodo-2'-deoxy-2'-fluoroadenosine；(2R,3R,4R,5R)-5-(6-amino-2-iodo-purin-9-yl)-4-fluoro-2-(hydroxymethyl)tetrahydrofuran-3-ol；(2R,3R,4R,5R)-5-(6-amino-2-iodopurin-9-yl)-4-fluoro-2-(hydroxymethyl)oxolan-3-ol
• CAS: 157762-25-9
• 化学式: C₁₀H₁₁FIN₅O₃
• 分子量: 395.132
• InChiKey: KUXMANZJOIXSJI-DXTOWSMRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2′-deoxy-2′-fluoro-2-iodoadenosine 在 potassium fluoride 作用下， 以 六甲基磷酰三胺 、 乙二醇二甲醚 为溶剂， 生成 2'-Deoxy-2,2'-difluoro-adenosine
  参考文献：
  名称：

  Synthesis and Anti-HIV Activity of 2-Substituted 2′-Deoxy-2′-fluoroadenosines

  摘要：

  2-Iodo-6-methoxypurine 2'-deoxy-2'-fluororiboside 8 was prepared from 2-iodo-6-methoxypurine riboside 1 in 8 steps. Reaction of 8 with ammonia in methanol gave the 2-iodoadenosine derivative 9 in 69% yield. Treatment of 9 with various nucleophiles gave 2-substituted analogues of 2'-deoxy-2'-fluoroadenosine 10-12. 2'-Deoxy-2,2'-difluoroadenosine 14 was also prepared by the treatment of the quaternary salt 13 with fluoride ion, but similar reactions of 13 with chloride or bromide ion gave the corresponding piperidine congeners 15a,b.

  DOI：

  10.1080/15257779408012146
• 作为产物：
  描述：

  2-iodo-6-methoxy-9-(2-O-acetyl-3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-β-D-arabinofuranosyl)purine 在 四丁基氟化铵 、 氨 、 4-甲基苯磺酸吡啶 、 对甲苯磺酸 、 溶剂黄146 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 作用下， 以 四氢呋喃 、 吡啶 、 甲醇 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.17h， 生成 2′-deoxy-2′-fluoro-2-iodoadenosine
  参考文献：
  名称：

  Synthesis and Anti-HIV Activity of 2-Substituted 2′-Deoxy-2′-fluoroadenosines

  摘要：

  2-Iodo-6-methoxypurine 2'-deoxy-2'-fluororiboside 8 was prepared from 2-iodo-6-methoxypurine riboside 1 in 8 steps. Reaction of 8 with ammonia in methanol gave the 2-iodoadenosine derivative 9 in 69% yield. Treatment of 9 with various nucleophiles gave 2-substituted analogues of 2'-deoxy-2'-fluoroadenosine 10-12. 2'-Deoxy-2,2'-difluoroadenosine 14 was also prepared by the treatment of the quaternary salt 13 with fluoride ion, but similar reactions of 13 with chloride or bromide ion gave the corresponding piperidine congeners 15a,b.

  DOI：

  10.1080/15257779408012146

文献信息

• Synthesis and Pharmacokinetic Evaluation of Siderophore Biosynthesis Inhibitors for <i>Mycobacterium tuberculosis</i>
  作者：Kathryn M. Nelson、Kishore Viswanathan、Surendra Dawadi、Benjamin P. Duckworth、Helena I. Boshoff、Clifton E. Barry、Courtney C. Aldrich

  DOI：10.1021/acs.jmedchem.5b00391

  日期：2015.7.23

  development. 5′-O-[N-(Salicyl)sulfamoyl]adenosine (1) is a bisubstrate inhibitor of MbtA and exhibits exceptionally potent biochemical and antitubercular activity. However, 1 suffers from suboptimal drug disposition properties resulting in a short half-life (t1/2), low exposure (AUC), and low bioavailability (F). Four strategies were pursued to address these liabilities including the synthesis of prodrugs

  MbtA催化分枝杆菌素的第一个重要的生物合成步骤，这是与结核分枝杆菌中铁摄入有关的重要毒力因子。MbtA是抗结核药物开发的经过验证的治疗靶标。5'- O- [ N-（水杨基）氨磺酰基]腺苷（1）是MbtA的双底物抑制剂，具有极强的生化和抗结核活性。然而，1的药物处置特性欠佳，导致半衰期短（t 1/2），低暴露（AUC）和低生物利用度（F）。采取了四种策略来解决这些问题，包括前药的合成，增加酰基磺酰基部分的p K a，调节亲脂性以及将氟引入1的策略。对所有化合物进行了完整的药代动力学（PK）分析。最成功的修饰涉及核苷的氟化，这可显着改善t 1/2和AUC。增加酰基-磺酰基接头的p K a会产生增量的增强，而亲脂性和前药方法的调节则导致PK参数大大降低。
• Synthesis and Anti-HIV Activity of 2-Substituted 2′-Deoxy-2′-fluoroadenosines
  作者：Tokumi Maruyama、Kunihiko Utsumi、Yoshiko Sato、Douglas D. Richman

  DOI：10.1080/15257779408012146

  日期：1994.7

  2-Iodo-6-methoxypurine 2'-deoxy-2'-fluororiboside 8 was prepared from 2-iodo-6-methoxypurine riboside 1 in 8 steps. Reaction of 8 with ammonia in methanol gave the 2-iodoadenosine derivative 9 in 69% yield. Treatment of 9 with various nucleophiles gave 2-substituted analogues of 2'-deoxy-2'-fluoroadenosine 10-12. 2'-Deoxy-2,2'-difluoroadenosine 14 was also prepared by the treatment of the quaternary salt 13 with fluoride ion, but similar reactions of 13 with chloride or bromide ion gave the corresponding piperidine congeners 15a,b.