L-dA | 14365-45-8

• 物质功能分类: 生物化工 - 核酸类
• 分子结构分类: 有机化合物 - 核苷、核苷酸和类似物 - 嘌呤核苷
• 英文名称: L-dA
• 英文别名: 9-(2-deoxy-β-L-ribofuranosyl)adenine；β-L-2'-deoxyadenosine；2'-desoxyadenosine；2'-deoxy-adenosine；9-(2-Deoxy-β-L-erythropentofuranosyl)adenine；2'-deoxy-L-adenosine；(2s,3r,5s)-5-(6-Amino-9h-Purin-9-Yl)-Tetrahydro-2-(Hydroxymethyl)furan-3-Ol；(2S,3R,5S)-5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol
• CAS: 14365-45-8
• 化学式: C₁₀H₁₃N₅O₃
• 分子量: 251.245
• InChiKey: OLXZPDWKRNYJJZ-VQVTYTSYSA-N

物化性质

• 熔点：
  186-187°C
• 沸点：
  627.2±65.0 °C(Predicted)
• 密度：
  1.91±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于二甲基亚砜、甲醇、水

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  119
• 氢给体数：
  3
• 氢受体数：
  7

安全信息

• 海关编码：
  2934999090
• 储存条件：
  存储条件：2-8°C，密封于干燥处。

制备方法与用途

2′-脱氧-L-腺苷是一种口服活性的合成子，能够用于修饰寡脱氧核糖核苷酸。它对乙型肝炎病毒(HBV)以及相关的鸭和土拨鼠肝炎病毒(WHV)的复制具有有效、特异且选择性的抑制作用。

反应信息

• 作为反应物：
  描述：

  L-dA 在 吡啶 、 4-二甲氨基吡啶 作用下， 生成 N-(9-{(2S,4R,5S)-5-[Bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-4-hydroxy-tetrahydro-furan-2-yl}-9H-purin-6-yl)-benzamide
  参考文献：
  名称：

  Enantio- and meso-DNAs: preparation, characterization, and interaction with complementary nucleic acids

  摘要：

  Enantio-DNAs (DNA having 2-deoxy-L-erythro-pentose, the enantiomer of natural 2-deoxy-D-ribose, as the sugar backbone) and meso-DNAs (DNA having an alternating sequence of L-sugars and D-sugars) were prepared by the use of an automated DNA synthesizer. The characteristics of the products were analyzed, focusing on enantio- and meso-dodecadeoxyadenylic acids (designated as L-dA12 and LD-dA12, respectively). Both L-dA12 and LD-dA12 were resistant to the action of phosphodiesterases, though LD-dA12 was decomposed very slowly by snake venom phosphodiesterase. The affinity of these dodecamers for their complementary natural nucleic acids, poly(U) and poly(dT), was analyzed by the UV-mixing curve and melting-temperature measurement methods. Both L-dA12 and LD-dA12 showed affinity for their complementary nucleic acids. L-dA12 showed high selectivity for poly(U) over poly(dT), and a UV-mixing curve analysis suggested that the interaction mode was triplex formation. LD-dA12 showed moderate selectivity for poly(U) over poly(dT). L-dT12, the counterpart of L-dA12, did not show any detectable interaction with its complementary natural nucleic acid.

  DOI：

  10.1021/ja00075a002
• 作为产物：
  描述：

  9-(2-O-acetyl-3,5-di-O-benzoyl-β-L-xylofuranosyl)adenine 在 水 、 乙醚 、 甲苯 、 甲醇 作用下， 以 溶剂黄146 为溶剂， 反应 5.0h， 以The desired 2′-deoxy-β-L-adenosine (β-L-dA) (0.12 g, 83%) was obtained的产率得到L-dA
  参考文献：
  名称：

  Methods of treating hepatitis delta virus infection with beta-l-2'-deoxy-nucleosides

  摘要：

  一种治疗患有丙型肝炎的宿主的方法和组合物，包括给予一定量的2'-脱氧-&bgr;-L-erythro-戊糖核苷或其药用可接受的盐或前药，以有效治疗丙型肝炎。

  公开号：

  US20020035085A1

文献信息

• 2'-deoxy-L-nucleosides
  申请人：Watanabe Kyoichi

  公开号：US20050090660A1

  公开（公告）日：2005-04-28

  This invention provides processes for the preparation of compounds having the structure: wherein X and Y are same or different, and H, OH, OR, SH, SR, NH 2 , NHR′, or NR′R″ Z is H, F, Cl, Br, I, CN, or NH 2 . R is hydrogen, halogen, lower alkyl of C 1 -C 6 or aralkyl, NO 2 , NH 2 , NHR′, NR′R″, OH, OR, SH, SR, CN, CONH 2 , CSNH 2 , CO 2 H, CO 2 R′, CH 2 CO 2 H, CH 2 CO 2 R′, CH═CHR, CH 2 CH═CHR, or C═CR. R′ and R″ are same or different, and lower alkyl of C 1 -C 6 . R 13 is hydrogen, alkyl, acyl, phosphate (monophosphate, diphosphate, triphosphate, or stabilized phosphate) or silyl; and

  这项发明提供了制备具有以下结构的化合物的方法： 其中 X和Y相同或不同，且H、OH、OR、SH、SR、NH2、NHR′或NR′R″ Z为H、F、Cl、Br、I、CN或NH2 R为氢、卤素、C1-C6的低碳烷基或芳基烷基、NO2、NH2、NHR′、NR′R″、OH、OR、SH、SR、CN、CONH2、CSNH2、CO2H、CO2R′、CH2CO2H、CH2CO2R′、CH═CHR、CH2CH═CHR或C═CR。 R′和R″相同或不同，且为C1-C6的低碳烷基。 R13为氢、烷基、酰基、磷酸酯（单磷酸酯、二磷酸酯、三磷酸酯或稳定磷酸酯）或硅基。
• [EN] PHOSPHORAMIDATE NUCLEOSIDE PRODRUG FOR TREATING VIRAL DISEASES AND CANCER, PROCESSES FOR THEIR PREPARATION AND THEIR USE<br/>[FR] PROMÉDICAMENT NUCLÉOSIDE PHOSPHORAMIDATE DESTINÉ AU TRAITEMENT DES MALADIES VIRALES ET DU CANCER, LEURS PROCÉDÉS DE PRÉPARATION ET LEUR UTILISATION
  申请人：IVACHTCHENKO ALEXANDRE VASILIEVICH

  公开号：WO2018022221A1

  公开（公告）日：2018-02-01

  The present invention pertains to chemotherapeutic agents and their use for treating viral and cancerous diseases. These compounds are inhibitors of HCV NS5B polymerase, HBV DNA polymerase and, HIV-1 reverse transcriptase (RT) inhibitor, and for treatment of hepatitis B and C infection in mammals. These compounds are also of interest for the treatment of cancer. The phosphoramidate nucleoside prodrug of the general formula (1), a stereoisomer, isotope-enriched analogue, pharmaceutically acceptable salt, hydrate, solvate, or crystalline or polymorphic form thereof, formula (1) wherein: Ar is aryl or hetaryl; R1 is H or CH3, R2 is the substituent selected from OCH2CH=CH2, OCH2CH≡CH, OCH2CH2CH2OCH3, formula (2), formula (3) or formula (4), R3 is H or CH3; R4 is OH, OR5, NR6R7; R5 is C1-C4-alkyl; R6 and R7 are not necessarily the same substituents selected from H or CH3, Z = O, or NH; an arrow (→) indicates the place of substituent connection; Nuc is formula (5) or (6); R8 and R9 are not necessarily the same substituents selected from H, F, Cl, CH3 or OH provided when continuous line and its accompanying dotted line ( ) together are the single carbon-carbon (C-C) bond or R8 and R9 are hydrogen provided when continuous line and its accompanying dotted line ( ) together are the double carbon-carbon bond (C=C); R10 is the substituent selected from R10.1- R10.5; R10.1 R10.2 R10.4 R10.5 ; R11 is the substituent selected from H, F, CI, CH3, or CF3; R12 is hydrogen, C1-C4-alkyl or C3-C6-cycloalkyl; X is oxygen or ethanediyl-1,1 (C=CH2); Y is O, S, CH2, or HO-CH group provided when continuous line and its accompanying dotted line (formula 7) together are the single carbon-carbon (C-C) bond or Y is CH group provided when continuous line and its accompanying dotted line (formula 7) together are the double carbon-carbon bond (C=C), and compound of the general formula (1), stereoisomers, isotope-enriched analogues, pharmaceutically acceptable salts, hydrates, solvates, or crystalline or polymorphic forms thereof, wherein: Ar is aryl or hetaryl; R1 is H or CH3; R2 is isopropyl; Nuc is formula (8), (9) or (10).

  本发明涉及化疗药物及其用于治疗病毒性和癌症疾病的用途。这些化合物是HCV NS5B聚合酶、HBV DNA聚合酶和HIV-1逆转录酶（RT）抑制剂，用于治疗哺乳动物中的乙型和丙型肝炎感染。这些化合物也对癌症治疗具有兴趣。通用式（1）的磷酰胺核苷前药的立体异构体、同位素富集类似物、药学上可接受的盐、水合物、溶剂合物或晶体或多形式，式（1）其中：Ar为芳基或杂芳基；R1为H或CH3，R2为从OCH2CH=CH2、OCH2CH≡CH、OCH2CH2CH2OCH3、式（2）、式（3）或式（4）中选择的取代基，R3为H或CH3；R4为OH、OR5、NR6R7；R5为C1-C4-烷基；R6和R7不一定相同，选择自H或CH3的取代基，Z=O或NH；箭头（→）表示取代基连接的位置；Nuc为式（5）或（6）；R8和R9不一定相同，选择自H、F、Cl、CH3或OH，提供当连续线及其相应的虚线（）一起为单碳-碳（C-C）键时，或R8和R9为氢，提供当连续线及其相应的虚线（）一起为双碳-碳键（C=C）时；R10为从R10.1-R10.5中选择的取代基；R10.1 R10.2 R10.4 R10.5；R11为从H、F、Cl、CH3或CF3中选择的取代基；R12为氢、C1-C4-烷基或C3-C6-环烷基；X为氧或乙烯二基-1,1（C=CH2）；Y为O、S、CH2或HO-CH基，提供当连续线及其相应的虚线（式7）一起为单碳-碳（C-C）键时，或Y为CH基，提供当连续线及其相应的虚线（式7）一起为双碳-碳键（C=C）时，以及通用式（1）的化合物、立体异构体、同位素富集类似物、药学上可接受的盐、水合物、溶剂合物或晶体或多形式，其中：Ar为芳基或杂芳基；R1为H或CH3；R2为异丙基；Nuc为式（8）、（9）或（10）。
• [EN] NOVEL 3´-DEOXY-3´-METHYLIDENE- -L-NUCLEOSIDES<br/>[FR] NOUVEAUX 3´-DÉSOXY-3´-MÉTHYLIDÈNE- -L-NUCLÉOSIDES
  申请人：NOVADEX PHARMACEUTICALS AB

  公开号：WO2011075052A1

  公开（公告）日：2011-06-23

  The present invention includes novel 3´-deoxy-3´-methylidene-β-L-nucleosides, pharmaceutical composition comprising such compounds, as well as the methods to treat or to prevent viral infections and in particular HBV and/or HIV infections. In accordance with the present invention, there are provided compounds represented by Formula (I), wherein B is selected from A1 and A2;

  本发明包括新颖的3´-去氧-3´-甲基亚-β-L-核苷，包括这些化合物的药物组合物，以及治疗或预防病毒感染，特别是HBV和/或HIV感染的方法。根据本发明，提供了由式（I）表示的化合物，其中B从A1和A2中选择。
• [EN] CYCLIC PHOSPHATE SUBSTITUTED NUCLEOSIDE DERIVATIVES FOR THE TREATMENT OF LIVER DISEASES<br/>[FR] DÉRIVÉS DE NUCLÉOSIDES CYCLIQUES À SUBSTITUTION PHOSPHATE POUR LE TRAITEMENT DE MALADIES HÉPATIQUES
  申请人：IDENIX PHARMACEUTICALS LLC

  公开号：WO2018091542A1

  公开（公告）日：2018-05-24

  The present invention relates to Compounds of Formula (I) or Formula (II) or a pharmaceutically acceptable salt, solvate or enantiomer thereof, wherein A, B, R1, R2, R3, R4, Q and V are as defined herein. The present invention also relates to pharmaceutical compositions comprising a Compound of Formula (I) or Formula (II) and to their use in therapy.

  本发明涉及式（I）或式（II）的化合物或其药用可接受的盐、溶剂化合物或对映体，其中A、B、R1、R2、R3、R4、Q和V如本文所定义。本发明还涉及包括式（I）或式（II）的化合物的药物组合物，并其在治疗中的应用。
• Meteorite-catalyzed intermolecular <i>trans</i>-glycosylation produces nucleosides under proton beam irradiation
  作者：Bruno Mattia Bizzarri、Angelica Fanelli、Michail Kapralov、Eugene Krasavin、Raffaele Saladino

  DOI：10.1039/d1ra02379a

  日期：——

  Di-glycosylated adenines act as glycosyl donors in the intermolecular trans-glycosylation of pyrimidine nucleobases under proton beam irradiation conditions. Formamide and chondrite meteorite NWA 1465 increased the yield and the selectivity of the reaction. The glycosyl transfer process was highly regioselective in yielding canonical N 1-pyrimidine nucleosides, the natural β-anomers prevailing in the

  在质子束照射条件下，二糖基化腺嘌呤在嘧啶核碱基的分子间反式糖基化中充当糖基供体。甲酰胺和球粒陨石 NWA 1465 提高了反应的产率和选择性。糖基转移过程在产生经典 N 1-嘧啶核苷方面具有高度区域选择性，这是在甲酰胺和 NWA 1465 存在下普遍存在的天然 β-异头物。这些数据突出了分子间反式糖基化在嘌呤和嘧啶的益生元形成中的可能作用核苷，避免出现独立的合成途径。