6-氯-9-(3,5-二-O-苯甲酰基-2-脱氧-2-氟-beta-D-阿拉伯呋喃糖基)-9H-嘌呤-2-胺 | 118373-61-8

• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 中文名称: 6-氯-9-(3,5-二-O-苯甲酰基-2-脱氧-2-氟-beta-D-阿拉伯呋喃糖基)-9H-嘌呤-2-胺
• 中文别名: 6-氯-9-(3,5-二-O-苯甲酰基-2-脱氧-2-氟-BETA-D-阿拉伯呋喃糖基)-9H-嘌呤-2-胺
• 英文名称: 2-amino-6-chloro-9-(3',5'-di-O-benzoyl-2'-deoxy-2'-fluoro-β-D-arabinofuranosyl)-9H-purine
• 英文别名: (2R,3R,4S,5R)-5-(2-amino-6-chloro-9H-purin-9-yl)-2-((benzoyloxy)methyl)-4-fluorotetrahydrofuran-3-yl benzoate；[(2R,3R,4S,5R)-5-(2-amino-6-chloropurin-9-yl)-3-benzoyloxy-4-fluorooxolan-2-yl]methyl benzoate
• CAS: 118373-61-8
• 化学式: C₂₄H₁₉ClFN₅O₅
• 分子量: 511.897
• InChiKey: NBBXMRVTXICTEV-VWFIUDSGSA-N

物化性质

• 沸点：
  735.1±70.0 °C(Predicted)
• 密度：
  1.58±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  36
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  10

制备方法与用途

2-氨基-6-氯嘌呤-9-β-D-(2'-脱氧-3',5'-二-O-苯甲酰基-2'-氟)阿糖胞苷是一种嘌呤核苷类似物，具有广泛的抗肿瘤活性，尤其针对惰性淋巴系统恶性肿瘤。其抗癌机制主要依赖于抑制DNA合成和诱导细胞凋亡等过程。

反应信息

• 作为反应物：
  描述：

  6-氯-9-(3,5-二-O-苯甲酰基-2-脱氧-2-氟-beta-D-阿拉伯呋喃糖基)-9H-嘌呤-2-胺 在 sodium methylate 、 2-巯基乙醇 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以72%的产率得到9-(2-脱氧-2-氟阿拉伯呋喃基)鸟嘌呤
  参考文献：
  名称：

  通过嘌呤衍生物的钾盐与糖基溴化物的选择性糖基化反应合成2'-脱氧-2'-氟-β-d-阿拉伯呋喃糖基嘌呤核苷

  摘要：

  9-（2-脱氧-2-氟-β - d-阿拉伯呋喃糖基）-鸟嘌呤（1）和-腺嘌呤（2）的合成是由容易获得的1,3,5-三-O-苯甲酰基-2-脱氧完成的-2-氟-α - d-阿拉伯呋喃糖（3）。利用α-1- O-苯甲酸酯的轻度溴化作用，开发了一种新的高效合成1-α-溴化物的方法（3）。溴糖与嘌呤钾盐的选择性偶联反应，然后对中间体封闭的2'-氟β-阿拉伯糖核苷进行衍生化和/或去保护，导致形成具有高总收率的目标化合物。

  DOI：

  10.1016/j.tetlet.2015.11.091
• 作为产物：
  描述：

  2-氨基-6-氯嘌呤 在 ammonium sulfate 、 四丁基氟化铵 、 氰化汞 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 11.65h， 生成 6-氯-9-(3,5-二-O-苯甲酰基-2-脱氧-2-氟-beta-D-阿拉伯呋喃糖基)-9H-嘌呤-2-胺
  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

• [EN] ECTONUCLEOTIDASE INHIBITORS AND METHODS OF USE THEREOF<br/>[FR] INHIBITEURS D'ÉCTONUCLÉOTIDASE ET LEURS MÉTHODES D'UTILISATION
  申请人：CALITHERA BIOSCIENCES INC

  公开号：WO2018119284A1

  公开（公告）日：2018-06-28

  The invention relates to novel heterocyclic compounds and pharmaceutical preparations thereof. The invention further relates to methods of treating or preventing cancer using the novel heterocyclic compounds of the invention.

  这项发明涉及新颖的杂环化合物及其制药制剂。该发明还涉及使用该发明的新颖杂环化合物治疗或预防癌症的方法。
• Synthesis and enzymatic resolution of carbocyclic 2′-ara-fluoro-guanosine: a potent new anti-herpetic agent
  作者：Alan D. Borthwick、Suzanne Butt、Keith Biggadike、Anne M. Exall、Stanley M. Roberts、Peter M. Youds、Barrie E. Kirk、Brian R. Booth、Janet M. Cameron、Susan W. Cox、Clara L. P. Marr、Mark D. Shill

  DOI：10.1039/c39880000656

  日期：——

  (±)-Carbocyclic-9-(2′-deoxy-2′-β-fluoroarabinofuranosyl) guanine (8) and the corresponding furanose compound (12) have been synthesised; the former compound [which was resolved by formation of the monophosphate (20) and enantioselective hydrolysis using a 5′-nucleotidase] is an extremely potent inhibitor of herpes simplex viruses types 1 and 2.

  合成了（±）-碳环-9-（2'-脱氧-2'-β-氟阿拉伯呋喃糖基）鸟嘌呤（8）和相应的呋喃糖化合物（12）；前一种化合物[通过形成单磷酸酯（20）和使用5'-核苷酸酶进行对映选择性水解而拆分]是一种非常有效的1型和2型单纯疱疹病毒抑制剂。
• Isolation, Synthesis, and Characterization of Impurities and Degradants from the Clofarabine Process
  作者：Bruce G. Anderson、William E. Bauta、William R. Cantrell, Jr.、Tracy Engles、Dennis P. Lovett

  DOI：10.1021/op800182x

  日期：2008.11.21

  process impurities and their subsequent isolation, synthesis, and characterization is described. Two isomeric process impurities resulting from N6-attachment of a fluoroarabinose to clofarabine were found. Clofarabine’s base degradation products, which were different from the process impurities, were also synthesized and characterized. These compounds resulted from modifications to the sugar moiety, the

  介绍了氯法拉滨工艺杂质的鉴定及其随后的分离，合成和表征。发现了由氟代阿拉伯糖的N 6-附着至氯法拉滨产生的两种异构过程杂质。还合成并表征了与工艺杂质不同的氯法拉滨的碱降解产物。这些化合物是由糖部分，嘌呤环或两者的修饰产生的。提供了用于形成各种工艺杂质和降解产物的机械原理。
• Synthesis and Biological Evaluation of Purine 2′-Fluoro-2′-deoxyriboside ProTides as Anti-influenza Virus Agents
  作者：Silvia Meneghesso、Evelien Vanderlinden、Andrea Brancale、Jan Balzarini、Lieve Naesens、Christopher McGuigan

  DOI：10.1002/cmdc.201200562

  日期：2013.3

  6‐O‐methyl‐2′‐fluoro‐2′‐deoxyguanosine, 6‐O‐ethyl‐2′‐fluoro‐2′‐deoxyguanosine, and 2′‐deoxy‐2′‐fluoro‐6‐chloroguanosine, and the 5′‐O‐naphthyl(ethoxy‐L‐alaninyl) ProTide of 6‐O‐ethyl‐2′‐fluoro‐2′‐deoxyguanosine displayed antiviral EC99 values of ∼12 μM. The antiviral results are supported by metabolism studies. Rapid conversion into the L‐alaninyl metabolite and then 6‐modified 2′‐fluoro‐2′‐deoxyguanosine

  据报道2'-氟-2'-脱氧鸟苷在体外和体内均具有有效的抗流感病毒活性。本文中，我们描述了6-修饰的2'-氟-2'-脱氧鸟苷类似物及其相应的氨基磷酸酯ProTides作为潜在的抗流感病毒制剂的合成和生物学评估。亲本核苷在两种不同的细胞分析中均没有抗病毒活性，而6 - O-甲基-2'-氟-2'-脱氧鸟苷的5'- O-萘基（甲氧基-L-丙氨酸）ProTide衍生物，6- ø -乙基-2'-氟-2'-脱氧鸟苷和2'-脱氧-2'-氟-6- chloroguanosine，和5'- Ò萘基（乙氧基大号-alaninyl）6- ProTide ö-乙基-2'-氟-2'-脱氧鸟苷抗病毒显示EC 99个的值〜12μ中号。抗病毒结果得到新陈代谢研究的支持。在用酵母羧肽酶Y或粗细胞裂解液进行酶法测定时，观察到迅速转化为L-丙氨酸代谢产物，然后迅速转化为6-修饰的2'-氟-2'-脱氧鸟苷5'-单磷酸酯。腺苷脱氨酶
• 抗ウィルス薬
  申请人：国立大学法人 長崎大学

  公开号：JP2020164521A

  公开（公告）日：2020-10-08

  【課題】本発明は、優れた抗ウィルス活性（特に抗Ｂ型肝炎ウィルス活性）を有する核酸アナログを提供する。【解決手段】下記の式（Ｉ）：（式中、各記号は本明細書中で定義した通りである）で表される化合物またはその塩。【選択図】なし

  This invention provides nucleoside analogs with excellent antiviral activity (especially anti-hepatitis B virus activity). The compound represented by the following formula (I): (wherein each symbol is as defined in the present specification) or its salt. No drawings are included.