N2-Isobutyryl-2'-O-(imidazol-1-yl)butylguanosine | 160527-02-6

• 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: N2-Isobutyryl-2'-O-(imidazol-1-yl)butylguanosine
• 英文别名: N-[9-[(2R,3R,4R,5R)-4-hydroxy-5-(hydroxymethyl)-3-(4-imidazol-1-ylbutoxy)oxolan-2-yl]-6-oxo-1H-purin-2-yl]-2-methylpropanamide
• CAS: 160527-02-6
• 化学式: C₂₁H₂₉N₇O₆
• 分子量: 475.505
• InChiKey: AXWNQFRCAQYGOW-KHTYJDQRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  34
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  165
• 氢给体数：
  4
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2'-O-[4-(imidazolyl-1)butyl]guanosine 、 异丁酰氯 在 三甲基氯硅烷 作用下， 以 吡啶 为溶剂， 生成 N2-Isobutyryl-2'-O-(imidazol-1-yl)butylguanosine
  参考文献：
  名称：

  Process for the preparation of 2'-O-alkyl purine phosphoramidites

  摘要：

  2'-O-烷基化鸟苷、尿苷、胞苷和2,6-二氨基嘌呤3'-O-磷酰胺酯是通过烷基化核苷前体、添加适当的阻断基团和磷酰化来制备的。烷基化是在2,6-二氨基-9-(β-D-核糖呋喃基)嘌呤上进行的，随后进行去氨基化以制备鸟苷2'-O-烷基化3'-O-磷酰胺酯。烷基化是在尿苷的二烷基基锡衍生物上进行的，以制备尿苷2'-O-烷基化3'-O-磷酰胺酯。烷基化是直接在胞苷上进行的，以制备胞苷2'-O-烷基化3'-O-磷酰胺酯。烷基化是直接在2,6-二氨基嘌呤上进行的，以制备2,6-二氨基嘌呤2'-O-烷基化3'-O-磷酰胺酯。

  公开号：

  US05646265A1

文献信息

• Process for the preparation of 2'-O-alkyl guanosine and related compounds
  申请人：ISIS Pharmaceuticals

  公开号：US05506351A1

  公开（公告）日：1996-04-09

  An improved process for preparing 2'-O-substituted guanosine comprising reacting an unprotected 2,6-diaminopurine riboside with an alkyl halide in the presence of a sodium hydride or a base of equal strength followed by a deamination step with adenosine deaminase. Such modified guanosine molecules can be used to synthesize 2'-O-modified oligonucleotides. The above alkylating process can also be used to prepare 3'-O-alkyl- and 2',3'-di-O-alkyl-2,6-diaminopurine ribosides. The deamination of these nucleosides yields the corresponding guanosine derivatives.

  一种改进的制备2'-O-取代鸟苷的方法，包括在氢氧化钠或等强碱的存在下，将未保护的2,6-二氨基嘌呤核苷与烷基卤素反应，随后进行腺苷脱氨酶的脱氨步骤。这种修改后的鸟苷分子可用于合成2'-O-修饰的寡核苷酸。上述烷基化过程也可用于制备3'-O-烷基-和2',3'-二-O-烷基-2,6-二氨基嘌呤核苷。这些核苷的脱氨作用会产生相应的鸟苷衍生物。
• Oligonucleotides containing 2'-0-modified purines
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US20040048826A1

  公开（公告）日：2004-03-11

  Novel 2′-O-alkyl guanosine compounds are provided. In accordance with preferred embodiments compounds having the structure: 1 wherein X is R 1 —(R 2 ) n ; R 1 is C 3 -C 20 alkyl, C 4 -C 20 alkenyl or C 2 -C 20 alkynyl; R 2 is halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides; and n is an integer from 0 to about 6, are provided.

  本发明提供了新型的2'-O-烷基鸟苷化合物。根据优选实施例，所提供的化合物具有以下结构：1其中X为R1-(R2)n；R1为C3-C20烷基、C4-C20烯基或C2-C20炔基；R2为卤素、羟基、硫醇、酮、羧基、硝基、亚硝基、腈、三氟甲基、三氟甲氧基、O-烷基、S-烷基、NH-烷基、N-二烷基、O-芳基、S-芳基、NH-芳基、O-芳基烷基、S-芳基烷基、NH-芳基烷基、氨基、N-邻苯二甲酰亚胺基、咪唑基、叠氮基、肼基、羟胺基、异氰酸酯基、亚砜基、磺酰基、硫醚基、二硫化物基、硅烷基、芳基、杂环、碳环、插入剂、报告分子、共轭物、多胺、多酰胺、多烷基氧基、多醚、增强寡核苷酸药效学性质的基团或增强寡核苷酸药代动力学性质的基团；n为0到约6的整数。
• Process for the preparation of 2′-O-alkyl-guanosine, cytidine, and uridine phosphoramidites
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US06242592B1

  公开（公告）日：2001-06-05

  Processes for preparing 2′-O-alkylated guanosine, uridine, cytidine, and 2,6-diaminopurine 3′-O-phosphoramidites include the steps of alkylating nucleoside precursors, adding suitable blocking groups and phosphitylating. For the guanosine 2′-O-alkylated 3′-O-phosphoramidites, alkylation is effected on 2,6-diamino-9-(&bgr;-D-ribofuranosyl) purine followed by deamination. For uridine 2′-O-alkylated 3′-O-phosphoramidites, alkylation is effect on a dialkyl stannylene derivative of uridine. For cytidine 2′-O-alkylated 3′-O-phosphoramidites, alkylation is effected directly on cytidine. Alkylation is effected directly upon 2,6-diaminopurine.

  制备2'-O-烷基化鸟苷、尿苷、胞苷和2,6-二氨基嘌呤3'-O-磷酰胺酯的过程包括烷基化核苷前体、添加适当的阻断基和磷酰化步骤。对于鸟苷2'-O-烷基化3'-O-磷酰胺酯，烷基化作用在2,6-二氨基-9-(&bgr;-D-核糖)嘌呤上，然后进行去氨作用。对于尿苷2'-O-烷基化3'-O-磷酰胺酯，烷基化作用在尿苷的二烷基锡衍生物上。对于胞苷2'-O-烷基化3'-O-磷酰胺酯，烷基化作用直接在胞苷上。烷基化作用直接作用在2,6-二氨基嘌呤上。
• 2'-O-modified nucleosides and phosphoramidites
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US05914396A1

  公开（公告）日：1999-06-22

  2'-O-Modified nucleosides, nucleotides, and oligonucleotides. These 2'-O-modified oligonucleotides are resistant to nuclease digestion and can effectively hybridize to a complementary polynucleotide.

  2'-O-修饰核苷、核苷酸和寡核苷酸。这些2'-O修饰的寡核苷酸能够抵抗核酸酶消化，能够有效地与互补的多核苷酸杂交。
• Oligonucleotides containing 2′-O-modified purines
  申请人：ISIS Pharmaceuticals, Inc.

  公开号：US07101993B1

  公开（公告）日：2006-09-05

  Compounds are provided containing purine nucleotides that bear moieties X at the 2′ position thereof wherein X is R1—(R2)n; R1 is C3-C20 alkyl, C4-C20 alkenyl or C2-C20 alkynyl; R2 is halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides; and n is an integer from 0 to about 6. Such compounds are useful for modulating the synthesis of proteins.

  提供含有嘌呤核苷酸的化合物，其中这些嘌呤核苷酸在其2'位点上带有X官能团，其中X是R1-(R2)n; R1是C3-C20烷基，C4-C20烯基或C2-C20炔基; R2是卤素，羟基，硫醇，酮，羧基，硝基，亚硝基，腈，三氟甲基，三氟甲氧基，O-烷基，S-烷基，NH-烷基，N-二烷基，O-芳基，S-芳基，NH-芳基，O-芳基烷基，S-芳基烷基，NH-芳基烷基，氨基，N-邻苯二甲酰亚胺基，咪唑，偶氮基，肼基，羟胺基，异氰酸酯，亚砜，砜，二硫化物，硅烷基，芳基，杂环，碳环，插入剂，报告分子，结合物，多胺，聚酰胺，聚烷基乙二醇，聚醚，增强寡核苷酸药效学性质的基团，或增强寡核苷酸药代动力学性质的基团; n是从0到约6的整数。这些化合物可用于调节蛋白质的合成。