N-苯甲酰基-5'-O-[二(4-甲氧基苯基)苯基甲基]-3'-脱氧-腺苷 2'-[2-氰基乙基二(1-甲基乙基)亚磷酰胺] | 207347-42-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 中文名称: N-苯甲酰基-5'-O-[二(4-甲氧基苯基)苯基甲基]-3'-脱氧-腺苷 2'-[2-氰基乙基二(1-甲基乙基)亚磷酰胺]
• 中文别名: N-苯甲酰基-5'-O-[二(4-甲氧基苯基)苯基甲基]-3'-脱氧-腺苷2'-[2-氰基乙基二(1-甲基乙基)亚磷酰胺]
• 英文名称: N⁶-benzoyl-3'-deoxy-5'-O-(4,4'-dimethoxytrityl)adenosine 2'-(2-cyanoethyl diisopropylphosphoramidite)
• 英文别名: (2R,3R,5S)-2-(6-Benzamido-9H-purin-9-yl)-5-((bis(4-methoxyphenyl)(phenyl)methoxy)methyl)tetrahydrofuran-3-yl (2-cyanoethyl) diisopropylphosphoramidite；N-[9-[(2R,3R,5S)-5-[[bis(4-methoxyphenyl)-phenylmethoxy]methyl]-3-[2-cyanoethoxy-[di(propan-2-yl)amino]phosphanyl]oxyoxolan-2-yl]purin-6-yl]benzamide
• CAS: 207347-42-0
• 化学式: C₄₇H₅₂N₇O₇P
• 分子量: 857.946
• InChiKey: JVRBQNAFQWBIAU-ILFCENRTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.9
• 重原子数：
  62
• 可旋转键数：
  19
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  155
• 氢给体数：
  1
• 氢受体数：
  12

制备方法与用途

N6-Bz-5'-O-DMTr-3'-脱氧腺苷-2'-O-CED磷酰胺是一种腺苷类似物，主要作为平滑肌血管扩张剂使用，并被证实能抑制癌症的进展。市面上的一些受欢迎产品包括磷酸腺苷、阿卡地辛(HY-13417)、氯法拉滨(HY-A0005)、磷酸氟达拉滨(HY-B0028)和维达拉宾(HY-B0277)。

反应信息

• 作为反应物：
  描述：

  N-苯甲酰基-5'-O-[二(4-甲氧基苯基)苯基甲基]-3'-脱氧-腺苷 2'-[2-氰基乙基二(1-甲基乙基)亚磷酰胺] 在 四氮唑 、 对甲苯磺酸 作用下， 以 甲醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 3.75h， 生成 N⁶-benzoyl-3'-deoxy-2'-adenylic acid 2-{[6-(benzoylamino)-9H-purin-9-yl]methoxy}ethyl 2-cyanoethyl ester
  参考文献：
  名称：

  Nucleotides Part LXX

  摘要：

  The chemical syntheses of nuclease-resistant, nontoxic bioactive (2'-5')agonists, 3'-deoxyadenylyl-(2'-->5')3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (d(3)A-d(3)A-d(3)A-etherA; 36), 1-benzyl-3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->2")-9-[2"-hydroxyethoxy)methyl]adenine (N-1-benzyl-d(3)A-d(3)A-d(3)A-etherA; 37), N-6-benzyl-3'-deoxyadenylyl-(2'-5')3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (N-6-benzyl-d(3)Ad(3)A-d(3)A-etherA; 38), N-6-benzyladenylyl-(2'-->5')-adenylyl-(2'-->5')-adenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (N-6-benzyl-A-A-A-etherA; 39), as well as the biological activities of 37, 38, and already synthesized and published adenylyl-(2'-->5')-adenylyl-(2'-->5')-adenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (A-A-A-etherA; 40), are described. The above (2'-5')A derivatives 37-40 inhibit HIV-1 replication as measured by inhibition of syncytia formation, HIV-1 reverse transcriptase activity, or HIV-1 p24-antigen expression, with no evidence of cytotoxicity. Oligonucleotides 37, 38, and 40 were taken up intact into T cells in culture of cytoplasmic concentrations sufficient to activate the latent endoribonuclease, RNase L. N-6-Benzyl-d(3)A-d(3)A-d(3)A-etherA (38) also exerts immunostimulatory effects by increasing expression of monocyte chemotactic protein-1 (MCP-1), and, thereby, competing with HIV-1 for binding to a critical HIV-coreceptor.

  DOI：

  10.1002/1522-2675(200208)85:8<2284::aid-hlca2284>3.0.co;2-e
• 作为产物：
  描述：

  虫草素 在 吡啶 、 四氮唑 、 N,N-二异丙基乙胺 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 5.0h， 生成 N-苯甲酰基-5'-O-[二(4-甲氧基苯基)苯基甲基]-3'-脱氧-腺苷 2'-[2-氰基乙基二(1-甲基乙基)亚磷酰胺]
  参考文献：
  名称：

  Nucleotides Part LXX

  摘要：

  The chemical syntheses of nuclease-resistant, nontoxic bioactive (2'-5')agonists, 3'-deoxyadenylyl-(2'-->5')3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (d(3)A-d(3)A-d(3)A-etherA; 36), 1-benzyl-3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->2")-9-[2"-hydroxyethoxy)methyl]adenine (N-1-benzyl-d(3)A-d(3)A-d(3)A-etherA; 37), N-6-benzyl-3'-deoxyadenylyl-(2'-5')3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (N-6-benzyl-d(3)Ad(3)A-d(3)A-etherA; 38), N-6-benzyladenylyl-(2'-->5')-adenylyl-(2'-->5')-adenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (N-6-benzyl-A-A-A-etherA; 39), as well as the biological activities of 37, 38, and already synthesized and published adenylyl-(2'-->5')-adenylyl-(2'-->5')-adenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (A-A-A-etherA; 40), are described. The above (2'-5')A derivatives 37-40 inhibit HIV-1 replication as measured by inhibition of syncytia formation, HIV-1 reverse transcriptase activity, or HIV-1 p24-antigen expression, with no evidence of cytotoxicity. Oligonucleotides 37, 38, and 40 were taken up intact into T cells in culture of cytoplasmic concentrations sufficient to activate the latent endoribonuclease, RNase L. N-6-Benzyl-d(3)A-d(3)A-d(3)A-etherA (38) also exerts immunostimulatory effects by increasing expression of monocyte chemotactic protein-1 (MCP-1), and, thereby, competing with HIV-1 for binding to a critical HIV-coreceptor.

  DOI：

  10.1002/1522-2675(200208)85:8<2284::aid-hlca2284>3.0.co;2-e

文献信息

• 环状二核苷酸化合物、其制备方法和应用
  申请人：上海弘翊生物科技有限公司

  公开号：CN109694397B

  公开（公告）日：2021-08-31

  本发明公开了环状二核苷酸化合物、其制备方法和应用，具体涉及一种式(I)所示的化合物，其药学上可接受的盐，其制备方法以及其在制备用于治疗和/或预防与激活STING蛋白相关的疾病的药物中的应用或作为疫苗佐剂的应用。所述与激活STING蛋白相关的疾病包括病毒感染，细菌感染，癌症，免疫系统相关疾病等。
• Novel Poxin Stable cGAMP‐Derivatives Are Remarkable STING Agonists
  作者：Samuele Stazzoni、Daniel F. R. Böhmer、Fabian Hernichel、Dilara Özdemir、Aikaterini Pappa、David Drexler、Stefan Bauernfried、Gregor Witte、Mirko Wagner、Simon Veth、Karl‐Peter Hopfner、Veit Hornung、Lars M. König、Thomas Carell

  DOI：10.1002/anie.202207175

  日期：2022.10.4

  Dideoxy-cyclic-dinucleotide analogs of cGAS/STING second messenger 2′,3′-cGAMP are prepared using a new and concise synthetic combination of phosphoramidite and phosphotriester chemistry. The dideoxy analogs are found to exhibit remarkable in cellulo and in vitro properties, are stable against degradation by poxvirus immune nucleases, and exhibit superior tumor growth control in a mouse model.

  cGAS/STING 第二信使 2′，3′-cGAMP 的二脱氧环二核苷酸类似物是使用亚磷酰胺和磷酸三酯化学的新颖简洁的合成组合制备的。发现双脱氧类似物在纤维素和体外特性中表现出显着的特性，对痘病毒免疫核酸酶的降解保持稳定，并且在小鼠模型中表现出卓越的肿瘤生长控制。
• Arslan, Tuncer; Abraham, Anil T.; Hecht, Sidney M., Nucleosides and Nucleotides, 1998, vol. 17, # 1-3, p. 515 - 530
  作者：Arslan, Tuncer、Abraham, Anil T.、Hecht, Sidney M.

  DOI：——

  日期：——
• Nucleotides Part LXX
  作者：Ramamurthy Charubala、Wolfgang Pfleiderer、Robert J. Suhadolnik、Kathryn T. Iacono、Nicholas F. Muto、Joseph W. Homan、Camille Martinand-Mari、Susan E. Horvath、Earl E. Henderson、Amber Steele、Thomas J. Rogers

  DOI：10.1002/1522-2675(200208)85:8<2284::aid-hlca2284>3.0.co;2-e

  日期：2002.8

  The chemical syntheses of nuclease-resistant, nontoxic bioactive (2'-5')agonists, 3'-deoxyadenylyl-(2'-->5')3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (d(3)A-d(3)A-d(3)A-etherA; 36), 1-benzyl-3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->2")-9-[2"-hydroxyethoxy)methyl]adenine (N-1-benzyl-d(3)A-d(3)A-d(3)A-etherA; 37), N-6-benzyl-3'-deoxyadenylyl-(2'-5')3'-deoxyadenylyl-(2'-->5')-3'-deoxyadenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (N-6-benzyl-d(3)Ad(3)A-d(3)A-etherA; 38), N-6-benzyladenylyl-(2'-->5')-adenylyl-(2'-->5')-adenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (N-6-benzyl-A-A-A-etherA; 39), as well as the biological activities of 37, 38, and already synthesized and published adenylyl-(2'-->5')-adenylyl-(2'-->5')-adenylyl-(2'-->2")-9-[(2"-hydroxyethoxy)methyl]adenine (A-A-A-etherA; 40), are described. The above (2'-5')A derivatives 37-40 inhibit HIV-1 replication as measured by inhibition of syncytia formation, HIV-1 reverse transcriptase activity, or HIV-1 p24-antigen expression, with no evidence of cytotoxicity. Oligonucleotides 37, 38, and 40 were taken up intact into T cells in culture of cytoplasmic concentrations sufficient to activate the latent endoribonuclease, RNase L. N-6-Benzyl-d(3)A-d(3)A-d(3)A-etherA (38) also exerts immunostimulatory effects by increasing expression of monocyte chemotactic protein-1 (MCP-1), and, thereby, competing with HIV-1 for binding to a critical HIV-coreceptor.