1-[5-O-benzoyl-2-deoxy-4-C-ethynyl-β-D-threo-pentofuranosyl]thymine | 744217-15-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1-[5-O-benzoyl-2-deoxy-4-C-ethynyl-β-D-threo-pentofuranosyl]thymine
• 英文别名: 1-[5-O-benzoyl-2-deoxy-4-ethynyl-β-D-threo-pentofuranosyl]thymine；1-[5-O-Benzoyl-2-deoxy-4-ethynyl-beta-D-threo-pentofuranosyl]thymine；[(2R,3R,5R)-2-ethynyl-3-hydroxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl benzoate
• CAS: 744217-15-0
• 化学式: C₁₉H₁₈N₂O₆
• 分子量: 370.362
• InChiKey: KVFNWXBIQVZSCN-SPYBWZPUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-[5-O-benzoyl-2-deoxy-4-C-ethynyl-β-D-threo-pentofuranosyl]thymine 在 吡啶 、 1,5-二氮杂双环[4.3.0]壬-5-烯 、 sodium methylate 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 15.0h， 生成 festinavir
  参考文献：
  名称：

  Anti-viral nucleoside analogs and methods for treating viral infections, especially HIV infections

  摘要：

  本发明涉及根据一般式I、II、III、IV或V的新化合物： 其中B是根据以下结构的核苷酸碱基： 以及规范中定义的其余变量，以及包含这些化合物的药物组合物。这些化合物可用作抗病毒剂，用于病毒治疗。

  公开号：

  US09126971B2
• 作为产物：
  描述：

  1-[5-O-benzoyl-3-O-(tert-butyldimethylsilyl)-4-chloro-2-deoxy-β-D-threo-pentofuranosyl]thymine 在 四丁基氟化铵 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 1.5h， 生成 1-[5-O-benzoyl-2-deoxy-4-C-ethynyl-β-D-threo-pentofuranosyl]thymine
  参考文献：
  名称：

  Nucleophilic Substitution at the 4‘-Position of Nucleosides: New Access to a Promising Anti-HIV Agent 2‘,3‘-Didehydro-3‘-deoxy-4‘-ethynylthymidine

  摘要：

  For the synthesis of 2',3'-didehydro-3'-deoxy-4'-ethynylthymidine (8: 4'-Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-L-glyceropent4- enofuranosyl) thymine with Pb(OBz) 4 allowed the introduction of the 4'-benzoyloxy leaving group, nucleophilic substitution at the 4'-position became feasible for the first time. Thus, reaction between the 4'-benzoyloxy derivative (14) and Me3SiC CAl(Et) Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (18) stereoselectively in 62% yield. As an application of this approach, other 4'-substituted nucleosides, such as the 4'-allyl (24a) and 4'-cyano (26a) derivatives, were synthesized using organosilicon reagents. In these instances, pretreatment of 14 with MeAlCl2 was necessary.

  DOI：

  10.1021/jo060194m

文献信息

• ANTI-VIRAL NUCLEOSIDE ANALOGS AND METHODS FOR TREATING VIRAL INFECTIONS, ESPECIALLY HIV INFECTIONS
  申请人：Cheng Yung-chi

  公开号：US20120252751A1

  公开（公告）日：2012-10-04

  The present invention relates to novel compounds according to the general formulas I, II, III, IV or V: wherein B is nucleoside base according to the structure: and the remaining variables as defined in the specification, and pharmaceutical compositions comprising the compounds. The compounds are useful interalia as anti-viral agents in viral therapy.

  本发明涉及一种新型化合物，其通式为I、II、III、IV或V：其中B是核苷酸碱基，其结构如下：其余变量如规范中所定义，并且包括这些化合物的药物组合物。这些化合物可用作抗病毒治疗中的抗病毒剂。
• Anti-viral nucleoside analogs and methods for treating viral infections, especially hiv infections
  申请人：Yale University

  公开号：EP2298783A1

  公开（公告）日：2011-03-23

  The present invention relates to novel compounds according to the general Formulae (I, II, III, IV or V); wherein B is nucleoside base according to the structure Formula (VI); R is H, F, Cl, Br, I, C1-C4 alkyl (preferably CH3), -C≡N, -C≡C-Ra, Formula (VII); X is H, C1-C4 alkyl (preferably CH3), F,Cl,Br or 1; Z is 0 or CH2 with the proviso that Z is CH2 and not O when the compound is according to general formula II, R3 is -C≡C-H and R2 is H or a phosphate, diphosphate, triphosphate or phosphotriester group; R1 is H, an acyl group, a C1-C20 alkyl or an ether group; R2 is H, an acyl group, a CI-C20 alkyl or ether group, a phosphate, diphosphate, triphosphate, phosphodiester group or a Formula; (VIII) or Formula (IX) group; Nu is a radical of a biologically active antiviral compound such that an amino group or hydroxyl group from said biologically active antiviral compound forms a phosphate, phosphoramidate, carbonate or urethane group with the adjacent moiety; R8 is H, or a C1-C20 alkyl or ether group, preferably a C1-C12 alkyl group; k is 0-12, preferably, 0-2; R3 is selected from a C1-C4 alkyl (preferably CH3), -(CH2)n-C=C-Ra, Formula (X) or Formula (XI); R3a and R3b are independently selected from H, F, C1, Br or I; R4 and R5 are independently selected from H, F, Cl, Br, I, OH, C1-C4 alkyl (preferably CH3),-(CH2)n-C≡C-Ra, Formula (XII) or Formula (XIII) with the proviso that R4 and R5 are not both H; Ra is H,F,Cl,Br,I or -C1-C4 alkyl, preferably H or CH3; Y is H, F, C1, Br, I or -C1-C4 alkyl, preferably H or CH3; and n is 0,1,2,3,4 or 5, preferably 0, 1 or 2; and their anomers, pharmaceutically acceptable salts, solvates or polymorphs thereof.

  本发明涉及根据通式(I，II，III，IV或V)的新型化合物；其中B是根据结构式(VI)的核苷碱；R是H，F，Cl，Br，I，C1-C4烷基(最好是CH3)，-C≡N，-C≡C-Ra，式(VII)；X是H，C1-C4烷基(最好是CH3)，F，Cl，Br或1；Z 是 0 或 CH2，但当化合物符合通式 II 时，Z 是 CH2 而不是 O，R3 是-C≡C-H，R2 是 H 或磷酸、二磷酸、三磷酸或磷酸三酯基团；R1 是 H、酰基、C1-C20 烷基或醚基；R2 是 H、酰基、CI-C20 烷基或醚基、磷酸酯、二磷酸酯、三磷酸 酯、磷酸二酯基团或式(VIII)或式(IX)基团；R8 是 H 或 C1-C20 烷基或醚基，最好是 C1-C12 烷基；k 是 0-12，最好是 0-2；R3 选自 C1-C4 烷基（最好是 CH3）、-(CH2)n-C=C-Ra、式 (X) 或式 (XI)；R3a 和 R3b 独立选自 H、F、C1、Br 或 I； R4 和 R5 独立选自 H、F、Cl、Br、I、OH、C1-C4 烷基（优选 CH3）、-(CH2)n-C≡C-Ra、式 (XII) 或式 (XIII)，但 R4 和 R5 不能都是 H；Ra是H、F、Cl、Br、I或-C1-C4烷基，最好是H或CH3；Y是H、F、C1、Br、I或-C1-C4烷基，最好是H或CH3；n是0、1、2、3、4或5，最好是0、1或2；以及它们的同分异构体、药学上可接受的盐、溶液或多晶型物。
• An Alternative Synthetic Method for 4′-C-Ethynylstavudine by Means of Nucleophilic Substitution of 4′-Benzoyloxythymine Nucleoside
  作者：Kazuhiro Haraguchi、Masanori Sumino、Hiromichi Tanaka

  DOI：10.1080/15257770701503969

  日期：2007.11.26

  For the synthesis of 2,3'-didehydro-3'-deoxy-4'-C-ethynylthymidine (8: 4'-Ed4T), a recently reported promising anti-HIV agent, a new approach was developed. Since treatment of 1-(2,5-dideoxy-beta-L-glycero-pent-4-enofuranosyl)thymine with Pb(OBz)(4) allowed the introduction of a 4'-benzoyloxy leaving group, nucleophilic substitution at the 4'-position became feasible, for the first time. Thus, reaction between the 4'-benzoyloxy derivative (H) and Me3SiC CAl(Et)Cl as a nucleophile led to the isolation of the desired 4'-"down"-ethynyl derivative (15) stereoselectively in 62 % yield.
• US7589078B2
  申请人：——

  公开号：US7589078B2

  公开（公告）日：2009-09-15
• US8193165B2
  申请人：——

  公开号：US8193165B2

  公开（公告）日：2012-06-05