5-(6-amino-purin-9-yl)-4-fluoro-cyclopent-3-ene-1,2-diol | 664302-82-3

• 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: 5-(6-amino-purin-9-yl)-4-fluoro-cyclopent-3-ene-1,2-diol
• 英文别名: (1S,2R,5S)-5-(6-Amino-purin-9-yl)-4-fluoro-cyclopent-3-ene-1,2-diol；(1S,2R,5S)-5-(6-aminopurin-9-yl)-4-fluorocyclopent-3-ene-1,2-diol
• CAS: 664302-82-3
• 化学式: C₁₀H₁₀FN₅O₂
• 分子量: 251.22
• InChiKey: BKOIRYNJVRCWLG-LPBLVHEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  110
• 氢给体数：
  3
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  (-)-(3Ar,6ar)-3a,6a-二氢-2,2-二甲基-4H-环戊并-1,3-二氧代-4-酮 在 吡啶 、 咪唑 、 sodium tetrahydroborate 、 正丁基锂 、 18-冠醚-6 、 cerium(III) chloride heptahydrate 、 四丁基氟化铵 、 水 、 碘 、 sodium hydride 、 N-氟代双苯磺酰胺 、 三乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 四氯化碳 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 生成 5-(6-amino-purin-9-yl)-4-fluoro-cyclopent-3-ene-1,2-diol
  参考文献：
  名称：

  X-ray Crystal Structure and Binding Mode Analysis of Human S-Adenosylhomocysteine Hydrolase Complexed with Novel Mechanism-Based Inhibitors, Haloneplanocin A Analogues

  摘要：

  The X-ray crystal structure of human S-adenosylhomocysteine (AdoHcy) hydrolase was first determined as a tetrameric form bound with the novel mechanism-based inhibitor fluoroneplanocin A (4b). The crystallized enzyme complex showed the closed conformation and turned out to be the intermediate of mechanism-based inhibition. It confirmed that the cofactor depletion by 3'-oxidation of fluoroneplanocin A contributes to the enzyme inhibition along with the irreversible covalent modification of AdoHcy hydrolase. In addition, a series of haloneplanocin A analogues (4b-e and 5b-e) were designed and synthesized to characterize the binding role and reactivity of the halogen substituents and the 4'-CH2OH group. The biological evaluation and molecular modeling studies identified the key pharmacophores and structural requirements for the inhibitor binding of AdoHcy hydrolase. The inhibitory activity was decreased as the size of the halogen atom increased and/or if the 4'-CH2OH group was absent. These results could be utilized to design new therapeutic agents operating via AdoHcy hydrolase inhibition.

  DOI：

  10.1021/jm1010836

文献信息

• Synthesis of Halogenated 9-(Dihydroxycyclopent-4′-enyl) Adenines and Their Inhibitory Activities Against<i>S</i>-Adenosylhomocysteine Hydrolase
  作者：Lak Shin Jeong、Jae Gyu Park、Won Jun Choi、Hyung Ryong Moon、Kang Man Lee、Hea Ok Kim、Hee-Doo Kim、Moon Woo Chun、Hea-Young Park、Kilhyoun Kim、Yhun Y. Sheen

  DOI：10.1081/ncn-120022686

  日期：2003.10

  Novel halovinyl analogues of neplanocin A without 4'-hydroxymethyl group were easily synthesized starting from D-ribose via cyclopentenone 5 as a key intermediate and their inhibitory activity against SAH hydrolase was assayed.
• Synthesis of fluorinated cyclopentenyladenine as potent inhibitor of S -adenosylhomocysteine hydrolase
  作者：Hea Ok Kim、Su Jeong Yoo、Hee Sung Ahn、Won Jun Choi、Hyung Ryong Moon、Kang Man Lee、Moon Woo Chun、Lak Shin Jeong

  DOI：10.1016/j.bmcl.2004.02.039

  日期：2004.5

  Fluoro-DHCeA (4) was efficiently synthesized from D-cyclopentenone derivative 5 using electrophilic fluorination as a key step. Fluoro-DHCeA (4) was found to be as potent as DHCeA (3), but exhibited irreversible inhibition of enzyme unlike DHCeA (3) showing reversible inhibition. From this Study, 4'-hydroxymethyl groups of neplanocin A and fluoro-neplanocin A played an important role in binding to the active site of the enzyme. (C) 2004 Elsevier Ltd. All rights reserved.
• Novel neplanocin derivatives
  申请人：MERRELL DOW PHARMACEUTICALS INC.

  公开号：EP0347852B1

  公开（公告）日：1995-08-23
• X-ray Crystal Structure and Binding Mode Analysis of Human <i>S</i>-Adenosylhomocysteine Hydrolase Complexed with Novel Mechanism-Based Inhibitors, Haloneplanocin A Analogues
  作者：Kang Man Lee、Won Jun Choi、Yoonji Lee、Hyun Joo Lee、Long Xuan Zhao、Hyuk Woo Lee、Jae Gyu Park、Hea Ok Kim、Kwang Yeon Hwang、Yong-Seok Heo、Sun Choi、Lak Shin Jeong

  DOI：10.1021/jm1010836

  日期：2011.2.24

  The X-ray crystal structure of human S-adenosylhomocysteine (AdoHcy) hydrolase was first determined as a tetrameric form bound with the novel mechanism-based inhibitor fluoroneplanocin A (4b). The crystallized enzyme complex showed the closed conformation and turned out to be the intermediate of mechanism-based inhibition. It confirmed that the cofactor depletion by 3'-oxidation of fluoroneplanocin A contributes to the enzyme inhibition along with the irreversible covalent modification of AdoHcy hydrolase. In addition, a series of haloneplanocin A analogues (4b-e and 5b-e) were designed and synthesized to characterize the binding role and reactivity of the halogen substituents and the 4'-CH2OH group. The biological evaluation and molecular modeling studies identified the key pharmacophores and structural requirements for the inhibitor binding of AdoHcy hydrolase. The inhibitory activity was decreased as the size of the halogen atom increased and/or if the 4'-CH2OH group was absent. These results could be utilized to design new therapeutic agents operating via AdoHcy hydrolase inhibition.