4'-Cyanothymidine | 139888-11-2

• 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: 4'-Cyanothymidine
• 英文别名: 4'-cyano-2'-deoxythymidine；(2R,3S,5R)-3-hydroxy-2-(hydroxymethyl)-5-(5-methyl-2.4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)tetrahydrofuran-2-carbonitrile；(2R,3S,5R)-3-hydroxy-2-(hydroxymethyl)-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolane-2-carbonitrile
• CAS: 139888-11-2
• 化学式: C₁₁H₁₃N₃O₅
• 分子量: 267.241
• InChiKey: LOOAUVYUIGMRGU-VAOFZXAKSA-N

物化性质

• 密度：
  1.56±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  19
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  123
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 4'-Cyanothymidine 以 四氢呋喃 为溶剂， 反应 17.0h， 以33.1 mg的产率得到3',5'-di-O-acetyl-4'-cyanothymidine
  参考文献：
  名称：

  利用4'-苯磺酰基离去基团对4'-取代的胸苷进行亲核取代的方法

  摘要：

  使用有机硅和有机铝试剂，基于亲核取代作用，研究了4'-取代的胸苷的合成。为此目的，制备具有苯磺酰的离去基团在4'位两个基板：1- [4-苯磺酰基-3,5-二- Ö - （叔丁基二甲基）-2-脱氧α-升-苏-戊呋喃糖基]胸腺嘧啶（8α）和4'-（苯磺酰基）胸腺嘧啶核苷衍生物（8β）。的反应8α用有机硅试剂（ME 3 SICH 2 CH CH 2和Me 3的SiN 3），其与组合的SnCl 4优先给出4′-取代的β- d-异构体：4′-烯丙基（12β）和4′-叠氮基（15β）衍生物。然而，推测8α与AlMe 3的反应产生了4′-甲基-α - l-异构体（16α）作为主要产物，推测是通过离子对机理。通过在该反应中使用底物8β，仅以高收率获得了4'-甲基胸苷衍生物（16β）。还通过使8β与相应的有机铝试剂反应合成了4'-乙基（20β）和4'-氰基（24β）衍生物。

  DOI：

  10.1016/j.tet.2009.05.078
• 作为产物：
  描述：

  3'-O-(叔丁基二甲基硅烷基)胸苷 在 吡啶 、 ammonium hydroxide 、 sodium hydroxide 、 盐酸羟胺 、 sodium acetate 、 乙酸酐 、 二甲基亚砜 、 三乙胺 、 N,N'-二环己基碳二亚胺 、 cesium fluoride 、 三氟乙酸 、 三氯乙酸酐 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 4'-Cyanothymidine
  参考文献：
  名称：

  Synthesis of 4′-cyanothymidine and analogs as potent inhibitors of HIV.

  摘要：

  4'-Cyanothymidine inhibits HIV in A301 (Alex) cells with an IC50 of 0.002-mu-M. The uridine and cytidine analogs show similar potencies.

  DOI：

  10.1016/s0040-4039(00)77667-2

文献信息

• 4'-substituted nucleosides
  申请人：Syntex (U.S.A.) Inc.

  公开号：US05192749A1

  公开（公告）日：1993-03-09

  Nucleosides compounds of Formula I: ##STR1## wherein B is a purine or a pyrimidine; X and X' are H; Y is H; Y' is OH, F or H; or Y' and X' together makes a bond; Z is ##STR2## where n is zero, one, two or three; or Y' and Z together form a cyclic phosphate ester; Z' is --CN, --CH.sub.3, CH.sub.2 N.sub.3 or --CH.sub.2 J, where J is a halogen atom; or Z' and Y' together are --CH.sub.2 O--; and pharmaceutically acceptable esters, ethers, amides, N-acyl moieties and salts thereof.

  核苷类化合物的化学式I：##STR1## 其中B是嘌呤或嘧啶；X和X'是H；Y是H；Y'是OH，F或H；或者Y'和X'一起形成键；Z是##STR2## 其中n为零、一、二或三；或者Y'和Z一起形成环磷酸酯；Z'是--CN，--CH.sub.3，CH.sub.2 N.sub.3或--CH.sub.2 J，其中J是卤素原子；或者Z'和Y'一起是--CH.sub.2 O--；以及其药用可接受的酯、醚、酰胺、N-酰基基团和盐。
• Anti-viral nucleoside analogs and methods for treating viral infections, especially HIV infections
  申请人：——

  公开号：US20040167096A1

  公开（公告）日：2004-08-26

  The present invention relates to novel compounds according to the to the general formulas I, II, III, IV or V: 1 wherein B is nucleoside base according to the structure: 2 R is H, F, Cl, Br, I, C 1 -C 4 alkyl (preferably CH 3 ), —C≡N, —C≡C—R a , 3 X is H, C 1 -C 4 alkyl (preferably, CH 3 ), F, Cl, Br or I; Z is O or CH 2 , with the proviso that Z is CH 2 and not O when the compound is according to general formula II, R 3 is —C≡C—H and R 2 is H or a phosphate, diphosphate, triphosphate or phosphotriester group; R 1 is H, an acyl group, a C 1 -C 20 alkyl or an ether group; R 2 is H, an acyl group, a C 1 -C 20 alkyl or ether group, a phosphate, diphosphate, triphosphate, phosphodiester group or a 4 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; R 8 is H, or a C 1 -C 20 alkyl or ether group, preferably a C 1 -C 12 alkyl group; k is 0-12, preferably, 0-2; R 3 is selected from a C 1 -C 4 alkyl (preferably, CH 3 ), —(CH 2 ) n —C≡C—R a , 5 R 3a and R 3b are independently selected from H, F, Cl, Br or I; R 4 and R 5 are independently selected from H, F, Cl, Br, I, OH, C 1 -C 4 alkyl (preferably, CH 3 ), —(CH 2 ) n —C≡C—R a , 6 with the proviso that R 4 and R 5 are not both H; R a is H, F, Cl, Br, I, or —C 1 -C 4 alkyl, preferably H or CH 3 ; Y is H, F, Cl, Br, I or —C 1 -C 4 alkyl, preferably H or CH 3 ; 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.

  本发明涉及符合一般式I、II、III、IV或V的新化合物：其中B是核苷酸碱基，如结构式2所示；R为H、F、Cl、Br、I、C1-C4烷基（优选为CH3）、—C≡N、—C≡C—Ra、3X为H、C1-C4烷基（优选为CH3）、F、Cl、Br或I；Z为O或CH2，但当化合物为一般式II时，Z为CH2而非O；R3为—C≡C—H，R2为H或磷酸酯、二磷酸酯、三磷酸酯或磷酸三酯基团；R1为H、酰基、C1-C20烷基或醚基；R2为H、酰基、C1-C20烷基或醚基、磷酸酯、二磷酸酯、三磷酸酯、磷酸二酯基团或a4基团；Nu为生物活性抗病毒化合物的基团，使得生物活性抗病毒化合物的氨基或羟基与相邻的基团形成磷酸酯、磷酰胺酸酯、碳酸酯或脲基团；R8为H或C1-C20烷基或醚基，优选为C1-C12烷基；k为0-12，优选为0-2；R3为选自C1-C4烷基（优选为CH3）、—（CH2）n—C≡C—Ra、5R3a和R3b独立选自H、F、Cl、Br或I；R4和R5独立选自H、F、Cl、Br、I、OH、C1-C4烷基（优选为CH3）、—（CH2）n—C≡C—Ra，但R4和R5不能同时为H；Ra为H、F、Cl、Br、I或—C1-C4烷基，优选为H或CH3；Y为H、F、Cl、Br、I或—C1-C4烷基，优选为H或CH3；n为0、1、2、3、4或5，优选为0、1或2；以及它们的异构体、药学上可接受的盐、溶剂或多晶体。
• [EN] NEW ANTI-MYCOBACTERIAL DRUGS AGAINST TUBERCULOSIS<br/>[FR] NOUVEAUX MÉDICAMENTS ANTI-MYCOBACTÉRIENS CONTRE LA TUBERCULOSE
  申请人：UNIV GEORGIA

  公开号：WO2013148174A1

  公开（公告）日：2013-10-03

  The present invention relates to the field of anti-mycobacterial therapeutics, in particular the treatment of tuberculosis, especially including pulmonary multidrug-resistant tuberculosis (MDR-TB), with applications in extensively drug-resistant tuberculosis (XDR-TB) and extremely drug-resistant tuberculosis (XXDR-TB), preferably in combination therapy.

  本发明涉及抗结核治疗领域，特别是肺部多药耐药结核病（MDR-TB）的治疗，包括广泛耐药结核病（XDR-TB）和极度耐药结核病（XXDR-TB），优选采用联合治疗。
• Pyridinone Diketo Acids: Inhibitors of HIV Replication in Combination Therapy
  申请人：Nair Vasu

  公开号：US20100092427A1

  公开（公告）日：2010-04-15

  A new class of diketo acids constructed on pyridinone scaffolds, designed as inhibitors of HTV replication through inhibition of HIV integrase, is described. These compounds are useful in the prevention or treatment of infection by HIV and in the treatment of AIDS and ARC, either as the compounds, or as pharmaceutically acceptable salts, with pharmaceutically acceptable carriers, used alone or in combination with antivirals, immunomodulators, antibiotics, vaccines, and other therapeutic agents, especially other anti-HIV compounds (including other anti-HIV integrase agents), which can be used to create combination anti-HIV cocktails. Methods of treating AIDS and ARC and methods of treating or preventing infection by HIV are also described. Compounds of the present application include those of formula I and include tautomers, regioisomers, geometric isomers, and pharmaceutically acceptable salts thereof, wherein the pyridinone scaffold and R groups are as otherwise defined in the specification. These are combined, with any number of typical other anti-HIV agents (including other integrase-based anti-HIV agents) and other combination therapeutic agents described herein, to provide an effective treatment modality for HIV infections, including AIDS and ARC.

  本文描述了一类新型的二酮酸，构建在吡啶酮支架上，设计用于通过抑制HIV整合酶来抑制HIV复制。这些化合物可用于预防或治疗HIV感染以及治疗AIDS和ARC，可以作为化合物本身或与药物载体结合使用，或与其他抗病毒药物、免疫调节剂、抗生素、疫苗和其他治疗剂联合使用，尤其是其他抗HIV化合物（包括其他抗HIV整合酶剂），以形成联合抗HIV药物组合。本申请的化合物包括公式I中的化合物和其中的互变异构体、区域异构体、几何异构体和其药学上可接受的盐，其中吡啶酮支架和R基在规范中另有定义。这些化合物与任意数量的典型其他抗HIV药物（包括其他基于整合酶的抗HIV药物）和其他联合治疗剂联合使用，提供了一种有效的治疗HIV感染的治疗模式，包括AIDS和ARC的治疗方法。
• 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。