N2-[(二甲氨基)亚甲基]鸟苷 | 1055407-32-3

• 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: N2-[(二甲氨基)亚甲基]鸟苷
• 英文名称: N-dimethylaminomethylene guanosine
• 英文别名: 2-N-(Dimethylformamidyl)guanosine；N-2-dimethylformamidine-guanosine；N²-[(dimethylamino)methylene]guanosine；N-[(Dimethylamino)methylene]-Guanosine；N'-[9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-oxo-1H-purin-2-yl]-N,N-dimethylmethanimidamide
• CAS: 1055407-32-3
• 化学式: C₁₃H₁₈N₆O₅
• 分子量: 338.323
• InChiKey: WDAVDBAMSKZBEN-PZYHSTABSA-N

物化性质

• 沸点：
  708.5±70.0 °C(Predicted)
• 密度：
  1.77±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  145
• 氢给体数：
  4
• 氢受体数：
  7

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  鸟苷	GUANOSINE	118-00-3	C10H13N5O5	283.244

• 下游产品

  中文名称	英文名称	CAS号	化学式	分子量
  ——	N'-[9-((2R,3R,5S)-3-Hydroxy-5-hydroxymethyl-tetrahydro-furan-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl]-N,N-dimethyl-formamidine	——	C13H18N6O4	322.324
  ——	(E)-N′-(9-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)-N,N-dimethylformimidamide	——	C13H18N6O4	322.324
  ——	5'-O-(4,4'-Dimethoxytrityl)-2-N-((dimethylamino)methylene)-3'-deoxyguanosine	——	C34H36N6O6	624.696
  ——	(E)-N′-(9-((2R,4S,5R)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)-methyl)-4-hydroxytetrahydrofuran-2-yl)-6-oxo-6,9-dihydro-1H-purin-2-yl)-N,N-dimethylformimidamide	——	C34H36N6O6	624.696
  ——	5'-O-(4,4'-Dimethoxytrityl)-2-N-((dimethylamino)methylene)-3'-O-(triisopropylsilyl)guanosine	——	C43H56N6O7Si	797.039
  ——	5'-O-(4,4'-Dimethoxytrityl)-2-N-((dimethylamino)methylene)-2'-O-(triisopropylsilyl)guanosine	——	C43H56N6O7Si	797.039
  ——	5'-O-(4,4'-Dimethoxytrityl)-2-N-((dimethylamino)methylene)-2'-O-(triisopropylsilyl)-3'-deoxyguanosine	——	C43H56N6O6Si	781.04
  ——	Imidazole-1-carbothioic acid O-{(2R,3R,4R,5R)-2-[bis-(4-methoxy-phenyl)-phenyl-methoxymethyl]-5-[2-(dimethylamino-methyleneamino)-6-oxo-1,6-dihydro-purin-9-yl]-4-triisopropylsilanyloxy-tetrahydro-furan-3-yl} ester	1053251-34-5	C47H58N8O7SSi	907.178
  ——	5'-O-(4,4'-Dimethoxytrityl)-2-N-((dimethylamino)methylene)-3'-deoxyguanosine 2'-O-(2-cyanoethyl N,N-diisopropylphosphoramidite)	——	C43H53N8O7P	824.917
  ——	5'-O-(4,4'-dimethoxytrityl)-3'-thioguanosine	247223-61-6	C31H31N5O6S	601.683

反应信息

• 作为反应物：
  描述：

  N2-[(二甲氨基)亚甲基]鸟苷 在 吡啶 、 咪唑 、 ammonium hydroxide 、 偶氮二异丁腈 、 四丁基氟化铵 、 三正丁基氢锡 、 溶剂黄146 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 53.0h， 生成 2'-脱氧鸟苷
  参考文献：
  名称：

  Preparation of 2'-O-(.beta.-Cyanoethyl phosphoramidites) of 3'-Deoxycytidine and 3'-Deoxyguanosine and Their Use for Solid-Phase Synthesis of Oligodeoxynucleotides Containing 2',5'-Phosphodiester Linkages

  摘要：

  Convenient, preparative scale synthetic routes to 2'-O-(beta-cyanoethyl N,N-diisopropylphosphoramidites) of 3'-deoxycytidine (1) and 3'-deoxyguanosine (2) are described. The 3'-deoxycytidine nucleoside 5 was constructed by a modified Hilbert-Johnson reaction in which N-(4-isobutyryl)-cytosine (4) was ribosylated with anomeric acetate 3. Nucleoside 5 was converted to 5'-O(dimethoxytrityl)-4-N-isobutyryl-3'-deoxycytidine (7) and phosphitylated to provide phosphoramidite 1. Access to derivatives of 3'-deoxyguanosine was provided by selective removal of the 3'-hydroxyl of guanosine (10). Thus, the 3'-O-thiocarbamate of 5'-O-(dimethoxytrityl)-2-N-(dimethylformamidyl)- 2'-O-(triisopropylsilyl)guanosine (12) was reduced with tributyltin hydride and converted to phosphoramidite 2. In results to be reported elsewhere, phosphoramidites 1 and 2 were used to prepare oligodeoxynucleotides containing novel 2',5'-phosphodiester linkages using automated solid-phase DNA synthesis methods with average stepwise coupling yields of >97%.

  DOI：

  10.1021/jo00103a014
• 作为产物：
  描述：

  N,N-二甲基甲酰胺二甲基缩醛 、 鸟苷 以 甲醇 为溶剂， 反应 96.0h， 以95%的产率得到N2-[(二甲氨基)亚甲基]鸟苷
  参考文献：
  名称：

  Preparation of 2'-O-(.beta.-Cyanoethyl phosphoramidites) of 3'-Deoxycytidine and 3'-Deoxyguanosine and Their Use for Solid-Phase Synthesis of Oligodeoxynucleotides Containing 2',5'-Phosphodiester Linkages

  摘要：

  Convenient, preparative scale synthetic routes to 2'-O-(beta-cyanoethyl N,N-diisopropylphosphoramidites) of 3'-deoxycytidine (1) and 3'-deoxyguanosine (2) are described. The 3'-deoxycytidine nucleoside 5 was constructed by a modified Hilbert-Johnson reaction in which N-(4-isobutyryl)-cytosine (4) was ribosylated with anomeric acetate 3. Nucleoside 5 was converted to 5'-O(dimethoxytrityl)-4-N-isobutyryl-3'-deoxycytidine (7) and phosphitylated to provide phosphoramidite 1. Access to derivatives of 3'-deoxyguanosine was provided by selective removal of the 3'-hydroxyl of guanosine (10). Thus, the 3'-O-thiocarbamate of 5'-O-(dimethoxytrityl)-2-N-(dimethylformamidyl)- 2'-O-(triisopropylsilyl)guanosine (12) was reduced with tributyltin hydride and converted to phosphoramidite 2. In results to be reported elsewhere, phosphoramidites 1 and 2 were used to prepare oligodeoxynucleotides containing novel 2',5'-phosphodiester linkages using automated solid-phase DNA synthesis methods with average stepwise coupling yields of >97%.

  DOI：

  10.1021/jo00103a014

文献信息

• Some observations relating to the use of 1-aryl-4-alkoxypiperidin-4-yl groups for the protection of the 2′-hydroxy functions in the chemical synthesis of oligoribonucleotides
  作者：Wayne Lloyd、Colin B. Reese、Quanlai Song、Anthony M. Vandersteen、Cristina Visintin、Pei-Zhou Zhang

  DOI：10.1039/a908149f

  日期：——

  The comparative rates of acid-catalysed removal of ten 1-aryl-4-methoxypiperidin-4-yl 8 (R = Me) [including the previously reported Ctmp 5 and Fpmp 6] protecting groups for the 2′-hydroxy functions in oligoribonucleotide synthesis are discussed. These studies have led to the development of the 1-(4-chlorophenyl)-4-ethoxypiperidin-4-yl (Cpep) protecting group 8 (R = Et, R1 = R2 = H, R3 = Cl) which is both more stable than the Ctmp and Fpmp groups at pH 0.5 and more labile at pH 3.75. The influence of the ribonucleoside aglycone on the stability of the 2′-O-Fpmp and 2′-O-Ctmp protecting groups both at low and high pH is examined.

  讨论了在寡核苷酸合成中，十个1-芳基-4-甲氧基哌啶-4-基（R = Me，包括先前报道的Ctmp 5和Fpmp 6）保护基对2'-羟基功能的酸催化去除的相对速率。这些研究导致开发了1-(4-氯苯基)-4-乙氧基哌啶-4-基（Cpep）保护基8（R = Et，R1 = R2 = H，R3 = Cl），其在pH 0.5下比Ctmp和Fpmp群更加稳定，而在pH 3.75下更加不稳定。研究了核苷酸基在低pH和高pH下对2'-O-Fpmp和2'-O-Ctmp保护基稳定性的影响。
• Solid-Phase Synthesis and On-Column Deprotection of RNA from 2‘- (and 3‘-) <i>O</i>-Levulinated (Lv) Ribonucleoside Monomers
  作者：Jeremy G. Lackey、David Sabatino、Masad J. Damha

  DOI：10.1021/ol0629521

  日期：2007.3.1

  [reaction: see text] The solid-phase synthesis of oligoribonucleotides derived from ribonucleosides esterified at the 2'- (or 3'-) position with the levulinyl (Lv) group is described. The oligomers can be released from the solid support as 2'-O-Lv ester derivatives or fully deprotected while still attached to the solid support.

  [反应：参见正文]描述了由核糖核苷衍生的寡核糖核苷酸的固相合成，所述核糖核苷在2'-（或3'-）位置被乙酰丙酰基（Lv）基团酯化。所述低聚物可以作为2′-O-Lv酯衍生物从固体载体上释放或完全脱保护，同时仍连接到固体载体上。
• NOVEL CYCLIC DINUCLEOTIDE DERIVATIVE AND ANTIBODY-DRUG CONJUGATE THEREOF
  申请人：Daiichi Sankyo Company, Limited

  公开号：EP3848054A1

  公开（公告）日：2021-07-14

  Desired is development of novel CDN derivatives having STING agonist activity; and a therapeutic agents and/or therapeutic methods using the novel CDN derivatives for diseases associated with STING agonist activity. Further desired is development of a therapeutic agents and/or therapeutic methods capable of delivering the novel CDN derivatives specifically to targeted cells and organs for diseases associated with STING agonist activity. The present invention provides novel CDN derivatives having potent STING agonist activity, and antibody-CDN derivative conjugates including the novel CDN derivatives.

  希望开发出具有 STING 激动剂活性的新型 CDN 衍生物；以及使用新型 CDN 衍生物治疗与 STING 激动剂活性相关疾病的治疗剂和/或治疗方法。还希望开发一种治疗剂和/或治疗方法，能够将新型 CDN 衍生物特异性地输送到靶细胞和器官，以治疗与 STING 激动剂活性相关的疾病。本发明提供了具有强效 STING 激动剂活性的新型 CDN 衍生物，以及包括新型 CDN 衍生物的抗体-CDN 衍生物共轭物。
• Cyclic dinucleotides for treating conditions associated with sting activity such as cancer
  申请人：Innate Tumor Immunity, Inc.

  公开号：US10604542B2

  公开（公告）日：2020-03-31

  This disclosure features dinucleotide compounds that modulate Stimulator of Interferon Genes (STING) activity, for use for example in the treatment of cancer. This disclosure also features compositions as well as other methods of using and making the same (Formula (A)). A and B are each independently selected from the group consisting of Formulae (i), (ii), (iii), and (iv).

  本公开具有调节干扰素基因刺激器（STING）活性的二核苷酸化合物，可用于治疗癌症等。本公开内容还包括组合物以及使用和制造组合物的其他方法（式（A））。A和B各自独立地选自式(i)、(ii)、(iii)和(iv)组成的组。
• Compounds and compositions for treating conditions associated with sting activity
  申请人：Innate Tumor Immunity, Inc.

  公开号：US10961270B2

  公开（公告）日：2021-03-30

  This disclosure features chemical entities (e.g., a compound that modulates (e.g., agonizes) Stimulator of Interferon Genes (STING), or a pharmaceutically acceptable salt, and/or hydrate, and/or cocrystal, and/or drug combination of the compound) that are useful, e.g., for treating a condition, disease or disorder in which a decrease or increase in STING activity (e.g., a decrease, e.g., a condition, disease or disorder associated with repressed or impaired STING signaling) contributes to the pathology and/or symptoms and/or progression of the condition, disease or disorder (e.g., cancer) in a subject (e.g., a human). This disclosure also features compositions as well as other methods of using and making the same.

  本公开的化学实体（例如，调节（例如，激动）干扰素基因刺激器（STING）的化合物，或该化合物的药学上可接受的盐、和/或水合物、和/或共晶体、和/或药物组合）有助于，例如、用于治疗 STING 活性降低或增加（例如，STING 信号转导受抑制或受损相关的状况、疾病或紊乱）导致受试者（例如人类）的病理和/或症状和/或状况、疾病或紊乱（例如癌症）进展的状况、疾病或紊乱。本公开的内容还包括组合物以及使用和制造组合物的其它方法。