(R)-2-((2-acetamido-1,6-dihydro-6-oxo-7H-purin-7-yl)methoxy)-4-chlorobutyl benzoate | 150943-39-8

• 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: (R)-2-((2-acetamido-1,6-dihydro-6-oxo-7H-purin-7-yl)methoxy)-4-chlorobutyl benzoate
• 英文别名: [(2R)-2-[(2-acetamido-6-oxo-1H-purin-7-yl)methoxy]-4-chlorobutyl] benzoate
• CAS: 150943-39-8
• 化学式: C₁₉H₂₀ClN₅O₅
• 分子量: 433.851
• InChiKey: JNUIYRHMFROVTK-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  124
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (R)-2-((2-acetamido-1,6-dihydro-6-oxo-7H-purin-7-yl)methoxy)-4-chlorobutyl benzoate 在 sodium hydroxide 、 phosphodiesterase 、 甲胺 作用下， 生成 (R)-ethyl hydrogen <3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutyl>phosphonate
  参考文献：
  名称：

  An Enantiospecific Synthesis of the Human Cytomegalovirus Antiviral Agent [(R)-3-((2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4- hydroxybutyl]phosphonic Acid

  摘要：

  The racemic isosteric phosphonate of ganciclovir monophosphate (BW2482U89, SR3745, [3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutyl]phosphonic acid, 1) has potent and selective in vitro;activity against human cytomegalovirus. An enantiospecific synthesis of the R-enantiomer of compound 1 starting from L-arabinose was developed. The synthesis involved (1) the preparation of a chiral acyclic moiety, (2) the coupling of the chiral acyclic moiety to diacetylguanine, (3) the introduction; of phosphorus, and (4) the final deprotection. The R-enantiomer, which has stereochemistry analogous to the natural compound GMP, was tested against human cytomegalovirus and had an IC50 Of 1.7 mu M, which was approximately 2-fold more active than the racemic material. Both racemic and chiral compounds were less toxic than ganciclovir to bone marrow progenitor cells in an in vitro assay.

  DOI：

  10.1021/jm00035a018
• 作为产物：
  描述：

  (R)-1-((tert-butyldiphenylsilyl)oxy)-4-chloro-2-(methoxymethoxy)butane 在 苯磺酰胺 、 三氟甲磺酸三甲基硅酯 、 四丁基氟化铵 作用下， 以 乙腈 为溶剂， 反应 22.25h， 生成 (R)-2-((2-acetamido-1,6-dihydro-6-oxo-7H-purin-7-yl)methoxy)-4-chlorobutyl benzoate
  参考文献：
  名称：

  An Enantiospecific Synthesis of the Human Cytomegalovirus Antiviral Agent [(R)-3-((2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4- hydroxybutyl]phosphonic Acid

  摘要：

  The racemic isosteric phosphonate of ganciclovir monophosphate (BW2482U89, SR3745, [3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutyl]phosphonic acid, 1) has potent and selective in vitro;activity against human cytomegalovirus. An enantiospecific synthesis of the R-enantiomer of compound 1 starting from L-arabinose was developed. The synthesis involved (1) the preparation of a chiral acyclic moiety, (2) the coupling of the chiral acyclic moiety to diacetylguanine, (3) the introduction; of phosphorus, and (4) the final deprotection. The R-enantiomer, which has stereochemistry analogous to the natural compound GMP, was tested against human cytomegalovirus and had an IC50 Of 1.7 mu M, which was approximately 2-fold more active than the racemic material. Both racemic and chiral compounds were less toxic than ganciclovir to bone marrow progenitor cells in an in vitro assay.

  DOI：

  10.1021/jm00035a018

文献信息

• [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.
• An Enantiospecific Synthesis of the Human Cytomegalovirus Antiviral Agent [(R)-3-((2-Amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4- hydroxybutyl]phosphonic Acid
  作者：Stanley D. Chamberlain、Karen K. Biron、Ronna E. Dornsife、Devron R. Averett、Lilia Beauchamp、George W. Koszalka

  DOI：10.1021/jm00035a018

  日期：1994.4

  The racemic isosteric phosphonate of ganciclovir monophosphate (BW2482U89, SR3745, [3-((2-amino-1,6-dihydro-6-oxo-9H-purin-9-yl)methoxy)-4-hydroxybutyl]phosphonic acid, 1) has potent and selective in vitro;activity against human cytomegalovirus. An enantiospecific synthesis of the R-enantiomer of compound 1 starting from L-arabinose was developed. The synthesis involved (1) the preparation of a chiral acyclic moiety, (2) the coupling of the chiral acyclic moiety to diacetylguanine, (3) the introduction; of phosphorus, and (4) the final deprotection. The R-enantiomer, which has stereochemistry analogous to the natural compound GMP, was tested against human cytomegalovirus and had an IC50 Of 1.7 mu M, which was approximately 2-fold more active than the racemic material. Both racemic and chiral compounds were less toxic than ganciclovir to bone marrow progenitor cells in an in vitro assay.