(+/-)-2-amino-1,9-dihydro-9-<(1α,2β,3β,4α)-2-fluoro-3-hydroxy-4-(hydroxymethyl)cyclopentyl>-6H-purin-6-one | 131101-25-2

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 核苷和核苷酸类似物
• 英文名称: (+/-)-2-amino-1,9-dihydro-9-<(1α,2β,3β,4α)-2-fluoro-3-hydroxy-4-(hydroxymethyl)cyclopentyl>-6H-purin-6-one
• 英文别名: 2-amino-9-[(1R,2S,3R,4R)-2-fluoro-3-hydroxy-4-(hydroxymethyl)cyclopentyl]-1H-purin-6-one
• CAS: 131101-25-2
• 化学式: C₁₁H₁₄FN₅O₃
• 分子量: 283.262
• InChiKey: RAXDGCQXNUHPMZ-MNCSTQPFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  126
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (+/-)-(1α,2β,3β,4α)-4-<(2-amino-6-chloro-4-pyrimidinyl)amino>-3-fluoro-2-hydroxycyclopentanemethanol 在 盐酸 、 sodium acetate 、 溶剂黄146 、 锌 作用下， 以 乙醇 、 水 为溶剂， 反应 7.5h， 生成 (+/-)-2-amino-1,9-dihydro-9-<(1α,2β,3β,4α)-2-fluoro-3-hydroxy-4-(hydroxymethyl)cyclopentyl>-6H-purin-6-one
  参考文献：
  名称：

  Fluorocarbocyclic nucleosides: synthesis and antiviral activity of 2'- and 6'-fluorocarbocyclic 2'-deoxyguanosines

  摘要：

  A series of four isomeric 2'- and 6'-fluorocarbocyclic guanosine analogues have been prepared and evaluated as potential anti-herpes agents. The racemic 2'-beta-fluoro isomer 2-amino-1,9-dihydro-9-[(1-alpha, 2-alpha, 3-beta, 4-alpha)-2-fluoro-3-hydroxy-4-(hydroxymethyl)cyclopenty]-6H-purin-6-one (11a, C-AFG) and its 2'-alpha-fluoro epimer 11b plus the chiral 6'-beta-fluoro isomer 2-amino-1,9-dihydro-9-[[1S-(1-alpha, 2-alpha, 3-alpha, 4-beta)]-2-fluoro-4-hydroxy-3-(hydroxymethyl)cyclopentyl]-6H-purin-6-one (11c) and its 6'-alpha-fluoro epimer 11d were prepared from their respective fluoro amino diol hydrochlorides (6a,d). For comparison, the furanosyl compound 9-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)guanine (17, AFG) was prepared by coupling 2-amino-6-chloropurine with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha-D-arabinofuranosyl bromide followed by base hydrolysis. The 6'-alpha-fluoro derivative 11d exhibited comparable activity to that of acyclovir (ACV) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro but was > 30-fold more active than ACV against HSV-1 and HSV-2 in vivo in the mouse systemic model. The 2'-beta-fluoro derivative (11a, C-AFG) was extremely potent in vitro against HSV-1 and HSV-2 (ID50 0.006 and 0.05-mu-g/mL) and in vivo it was greater than 2 orders of magnitude more potent than ACV against HSV-1 and 70-fold more potent against HSV-2. The 2'-alpha-fluoro 11b and 6'-beta-fluoro 11c isomers were much less active.

  DOI：

  10.1021/jm00107a006

文献信息

• Fluorocarbocyclic nucleosides: synthesis and antiviral activity of 2'- and 6'-fluorocarbocyclic 2'-deoxyguanosines
  作者：Alan D. Borthwick、Barrie E. Kirk、Keith Biggadike、Anne M. Exall、Suzanne Butt、Stanley M. Roberts、David J. Knight、Jonathan A. V. Coates、D. Michael Ryan

  DOI：10.1021/jm00107a006

  日期：1991.3

  A series of four isomeric 2'- and 6'-fluorocarbocyclic guanosine analogues have been prepared and evaluated as potential anti-herpes agents. The racemic 2'-beta-fluoro isomer 2-amino-1,9-dihydro-9-[(1-alpha, 2-alpha, 3-beta, 4-alpha)-2-fluoro-3-hydroxy-4-(hydroxymethyl)cyclopenty]-6H-purin-6-one (11a, C-AFG) and its 2'-alpha-fluoro epimer 11b plus the chiral 6'-beta-fluoro isomer 2-amino-1,9-dihydro-9-[[1S-(1-alpha, 2-alpha, 3-alpha, 4-beta)]-2-fluoro-4-hydroxy-3-(hydroxymethyl)cyclopentyl]-6H-purin-6-one (11c) and its 6'-alpha-fluoro epimer 11d were prepared from their respective fluoro amino diol hydrochlorides (6a,d). For comparison, the furanosyl compound 9-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)guanine (17, AFG) was prepared by coupling 2-amino-6-chloropurine with 2-deoxy-2-fluoro-3,5-di-O-benzoyl-alpha-D-arabinofuranosyl bromide followed by base hydrolysis. The 6'-alpha-fluoro derivative 11d exhibited comparable activity to that of acyclovir (ACV) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in vitro but was > 30-fold more active than ACV against HSV-1 and HSV-2 in vivo in the mouse systemic model. The 2'-beta-fluoro derivative (11a, C-AFG) was extremely potent in vitro against HSV-1 and HSV-2 (ID50 0.006 and 0.05-mu-g/mL) and in vivo it was greater than 2 orders of magnitude more potent than ACV against HSV-1 and 70-fold more potent against HSV-2. The 2'-alpha-fluoro 11b and 6'-beta-fluoro 11c isomers were much less active.