<1R-(1α,2β,3α,5β)>-3-<(2-amino-6-chloro-4-pyrimidinyl)amino>-2-fluoro-5-hydroxycyclopentanemethanol | 131101-19-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: <1R-(1α,2β,3α,5β)>-3-<(2-amino-6-chloro-4-pyrimidinyl)amino>-2-fluoro-5-hydroxycyclopentanemethanol
• 英文别名: (1R-(1α,2β,3α,5β))-3-[(2-amino-6-chloro-4-pyrimidinyl)amino]-2-fluoro-5-hydroxycyclopentanemethanol；(1S,2R,3S,4S)-4-[(2-amino-6-chloropyrimidin-4-yl)amino]-3-fluoro-2-(hydroxymethyl)cyclopentan-1-ol
• CAS: 131101-19-4
• 化学式: C₁₀H₁₄ClFN₄O₂
• 分子量: 276.698
• InChiKey: QGRYFPBPPLAWGH-OLHMAJIHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  104.29
• 氢给体数：
  4.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  <1R-(1α,2β,3α,5β)>-3-<(2-amino-6-chloro-4-pyrimidinyl)amino>-2-fluoro-5-hydroxycyclopentanemethanol 在 sodium acetate 、 溶剂黄146 、 锌 作用下， 以 乙醇 、 水 为溶剂， 反应 1.0h， 生成 <1R-(1α,2β,3α,5β)>-3-<(2,5-diamino-6-chloro-4-pyrimidinyl)amino>-2-fluoro-5-hydroxycyclopentanemethanol
  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
• 作为产物：
  描述：

  <1S-(1α,2β,3α,4β)>-2-fluoro-4-(phenylmethoxy)-3-<(phenylmethoxy)methyl>-1-cyclopentanamine 在 palladium on activated charcoal 盐酸 、 氢气 、 三乙胺 作用下， 以 甲醇 、 乙醇 为溶剂， 反应 51.0h， 生成 <1R-(1α,2β,3α,5β)>-3-<(2-amino-6-chloro-4-pyrimidinyl)amino>-2-fluoro-5-hydroxycyclopentanemethanol
  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

• BORTWICK, A. D.;KIRK, B. E.;BIGGADIKE, KEITH;EXALL, ANNE M.;BUTT, SUZANNE+, J. MED. CHEM., 34,(1991) N, C. 1834
  作者：BORTWICK, A. D.、KIRK, B. E.、BIGGADIKE, KEITH、EXALL, ANNE M.、BUTT, SUZANNE+

  DOI：——

  日期：——