(S)-3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutylphosphonic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: (S)-3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutylphosphonic acid
• 英文别名: (S)-ganciclovir phosphonate；9-[(S(+)-1-Hydroxymethyl-3-phosphono) propyl-oxymethyl] guanine；[(3S)-3-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]-4-hydroxy-butyl]phosphonic acid；[(3S)-3-[(2-amino-6-oxo-1H-purin-9-yl)methoxy]-4-hydroxybutyl]phosphonic acid
• 化学式: C₁₀H₁₆N₅O₆P
• 分子量: 333.241
• InChiKey: QVNXYSKNFUJRMI-LURJTMIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.3
• 重原子数：
  22
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  172
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (S)-3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutylphosphonic acid 在 GMP kinase from numan red blood cells 作用下， 生成 (S)-3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutylphosphonic acid monophosphate
  参考文献：
  名称：

  Phosphorylation of Ganciclovir Phosphonate by Cellular GMP Kinase Determines the Stereoselectivity of Anti-Human Cytomegalovirus Activity

  摘要：

  A racemic mixture of ganciclovir phosphonate was resolved by stereoselective phosphorylation using GMP kinase. The R-enantiomer of ganciclovir phosphonate was active against human cytomegalovirus but the S-enantiomer was less active. We show that enantiomeric selectivity of antiviral activity for ganciclovir phosphonate was conferred by stereoselective phosphorylations by mammalian enzymes, not by stereoslective inhibition of DNA polymerase from human cytomegalovirus.

  DOI：

  10.1080/15257770008033013
• 作为产物：
  描述：

  [3-[(2-氨基-6-氧代-3H-嘌呤-9-基)甲氧基]-4-羟基丁基]膦酸 在 GMP kinaze from porcine brain 、 5’-三磷酸腺苷 、 magnesium chloride 作用下， 以 水 为溶剂， 反应 5.0h， 生成 (S)-3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutylphosphonic acid 、 3-((2-amino-1,6-dihydro-6-oxo-7H-purin-7-yl)methoxy)-4-hydroxybutylphosphonic acid 、 (R)-3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutylphosphonic acid monophosphate
  参考文献：
  名称：

  Phosphorylation of Ganciclovir Phosphonate by Cellular GMP Kinase Determines the Stereoselectivity of Anti-Human Cytomegalovirus Activity

  摘要：

  A racemic mixture of ganciclovir phosphonate was resolved by stereoselective phosphorylation using GMP kinase. The R-enantiomer of ganciclovir phosphonate was active against human cytomegalovirus but the S-enantiomer was less active. We show that enantiomeric selectivity of antiviral activity for ganciclovir phosphonate was conferred by stereoselective phosphorylations by mammalian enzymes, not by stereoslective inhibition of DNA polymerase from human cytomegalovirus.

  DOI：

  10.1080/15257770008033013

文献信息

• US5532225A
  申请人：——

  公开号：US5532225A

  公开（公告）日：1996-07-02
• [EN] ACYCLIC PURINE PHOSPHONATE NUCLEOTIDE ANALOGS AS ANTIVIRAL AGENTS, AND RELATED SYNTHETIC METHODS<br/>[FR] ANALOGUES DE NUCLEOTIDES PHOSPHONATES DE PURINE ACYCLIQUE UTILES COMME AGENTS ANTIVIRAUX ET PROCEDES SYNTHETIQUES CONNEXES
  申请人：SRI INTERNATIONAL

  公开号：WO1994003466A1

  公开（公告）日：1994-02-17

  (EN) Acyclic purine phosphonate nucleotide analogs useful to treat herpes viral infections are provided in enantiomerically pure form. These antiviral agents have structural formula (Ia) or (Ib), and may be in acid, salt or ester form. Such compounds may also be dehydrated to provide antiviral agents in cyclic form. Pharmaceutical compositions are provided containing the antiviral agents, as is a chiral synthesis which may be used to prepare the agents in enantiomerically pure form or as a racemic mixture.(FR) Des analogues de nucléotides phosphonatés de purine acyclique utilisés dans le traitement des infections virales de l'herpès sont obtenus sous une forme énantiomériquement pure. Ces agents antiviraux ont la formule structurelle (Ia) ou (Ib) et peuvent être sous forme d'acides, de sels ou d'esters. Ces composés peuvent également être déshydratés afin d'obtenir des agents antiviraux sous forme cyclique. On produit également des compositions pharmaceutiques contenant les agents antiviraux comme dans une synthèse chirale qui peut être utilisée pour préparer les agents sous forme énantiomériquement pure ou comme mélange racémique.
• [EN] THERAPEUTIC NUCLEOSIDES
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：WO1993006112A1

  公开（公告）日：1993-04-01

  (EN) The present invention relates to an antiviral phosphonate derivate of an acyclic purine nucleoside analog, to pharmaceutically acceptable derivatives thereof and to their use in medical therapy, particularly in the treatment of cytomegalovirus infections. Methods for preparing the R-enantiomer of the compound of the invention, substantially free from the corresponding S-enantiomer are disclosed.(FR) La présente invention se rapporte à un dérivé de phosphonate antiviral d'un analogue de nucléoside de purine acyclique, à des dérivés pharmaceutiquement acceptables, ainsi qu'à leur utilisation en thérapie médicale, en particulier pour le traitement d'infections par cytomégalovirus. Des procédés de préparation de l'énantiomère-R du composé de l'invention, lequel est pratiquement dépourvu de l'énantiomère-S correspondant, sont également décrits.
• Phosphorylation of Ganciclovir Phosphonate by Cellular GMP Kinase Determines the Stereoselectivity of Anti-Human Cytomegalovirus Activity
  作者：Wayne H. Miller、Lilia M. Beauchamp、Eric Meade、John E. Reardon、Karen K. Biron、Albert A. Smith、Charles A. Goss、Richard L. Miller

  DOI：10.1080/15257770008033013

  日期：2000.1

  A racemic mixture of ganciclovir phosphonate was resolved by stereoselective phosphorylation using GMP kinase. The R-enantiomer of ganciclovir phosphonate was active against human cytomegalovirus but the S-enantiomer was less active. We show that enantiomeric selectivity of antiviral activity for ganciclovir phosphonate was conferred by stereoselective phosphorylations by mammalian enzymes, not by stereoslective inhibition of DNA polymerase from human cytomegalovirus.