2,2-dimethylpropyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-ethoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-[[(2S)-1-(2,2-dimethylpropoxy)-1-oxopropan-2-yl]amino]phosphoryl]amino]propanoate | 1350765-96-6

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷酸
• 英文名称: 2,2-dimethylpropyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-ethoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-[[(2S)-1-(2,2-dimethylpropoxy)-1-oxopropan-2-yl]amino]phosphoryl]amino]propanoate
• CAS: 1350765-96-6
• 化学式: C₂₉H₅₀N₇O₁₀P
• 分子量: 687.731
• InChiKey: VQWLOEMJIHYRAF-XSNSQEFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  47
• 可旋转键数：
  18
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.76
• 拓扑面积：
  232
• 氢给体数：
  5
• 氢受体数：
  16

反应信息

• 作为产物：
  描述：

  L-alanine neopentyl ester tosylate 、 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以80 mg的产率得到2,2-dimethylpropyl (2S)-2-[[[(2R,3R,4R,5R)-5-(2-amino-6-ethoxypurin-9-yl)-3,4-dihydroxy-4-methyloxolan-2-yl]methoxy-[[(2S)-1-(2,2-dimethylpropoxy)-1-oxopropan-2-yl]amino]phosphoryl]amino]propanoate
  参考文献：
  名称：

  Phosphorodiamidates as a Promising New Phosphate Prodrug Motif for Antiviral Drug Discovery: Application to Anti-HCV Agents

  摘要：

  We herein report phosphorodiamidates as a significant new phosphate prodrug motif. Sixty-seven phosphorodiamidates are reported of two 6-O-alkyl 2'-C-methyl guanosines, with significant variation in the diamidate structure. Both symmetrical and asymmetric phosphorodiamidates are reported, derived from various esterified amino acids, both D and L., and also from various simple amines. All of the compounds were evaluated versus hepatitis C virus in replicon assay, and nanomolar activity levels were observed. Many compounds were noncytotoxic at 100 mu M, leading to high antiviral selectivities. The agents are stable in acidic, neutral, and moderately basic media and in selected biological media but show efficient processing by carboxypeptidases and efficiently yield the free nucleoside monophosphate in cells. On the basis of in vitro data, eight leads were selected for additional in vivo evaluation, with the intent of selecting one candidate for progression toward clinical studies. This phosphorodiamidate prodrug method may have broad application outside of HCV and antivirals as it offers many of the advantages of phosphoramidate ProTides but without the chirality issues present in most cases.

  DOI：

  10.1021/jm2011673

文献信息

• [EN] PHOSPHORODIAMIDATE DERIVATIVES OF GUANOSINE NUCLEOSIDE COMPOUNDS FOR TREATMENT OF VIRAL INJECTIONS<br/>[FR] DÉRIVÉS PHOSPHORODIAMIDATE DE COMPOSÉS NUCLÉOSIDIQUES À BASE DE GUANOSINE DESTINÉS À TRAITER DES INFECTIONS VIRALES
  申请人：INHIBITEX INC

  公开号：WO2012048013A2

  公开（公告）日：2012-04-12

  This invention is directed to novel compounds of formula (I) having the structure that are useful in the treatment of viral infections in mammals mediated, at least in part, by a virus in the Flaviviridae family of viruses. Methods of treating viral infections via administration of these compounds are also disclosed.