4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-6-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine | 38925-85-8

• 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: 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-6-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine
• 英文别名: 2-(methylthio)-2'-deoxyadenosine；8-aza-7-deaza-2'-deoxy-2-(methylsulfanyl)adenosine；S-methyl-2-thio-2'-deoxy-isoguanosine；(2R,3S,5R)-5-(6-amino-2-methylsulfanylpurin-9-yl)-2-(hydroxymethyl)oxolan-3-ol
• CAS: 38925-85-8
• 化学式: C₁₁H₁₅N₅O₃S
• 分子量: 297.338
• InChiKey: BWIFEKCVNQIESD-RRKCRQDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  145
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-6-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine 在 磷酸三甲酯 、 Proton Sponge 、 三氯氧磷 作用下， 反应 1.0h， 生成 [(2R,3S,5R)-5-(6-amino-2-methylsulfanylpurin-9-yl)-2-(phosphonooxymethyl)oxolan-3-yl] dihydrogen phosphate
  参考文献：
  名称：

  脱氧腺苷二磷酸衍生物作为 P2Y1 受体的有效拮抗剂。

  摘要：

  腺苷3',5'-和2',5'-二磷酸先前被证明可作为P2Y1受体的竞争性拮抗剂(Boyer等人Mol.Pharmacol.1996, 50, 1323-1329)。已合成了 2'- 和 3'-脱氧腺苷二磷酸类似物，在腺嘌呤环的 2- 和 6- 位、核糖部分和磷酸基团上含有各种结构修饰，目的是开发更有效和选择性的 P2Y1对手。进行了腺苷核苷前体的一步磷酸化反应。通过测量其刺激火鸡红细胞膜中磷脂酶 C（激动剂作用）和抑制 10 nM 2-MeSATP 引起的磷脂酶 C 刺激（拮抗剂作用）的能力，确定每种类似物对 P2Y1 受体的活性。 2'-和3'-脱氧修饰均具有良好的耐受性。 N6-甲基修饰既增强​​了 2'-脱氧腺苷 3',5'-二磷酸的拮抗效力 (IC50 330 nM) 17 倍，又消除了先导化合物观察到的残留激动剂特性。 N6-乙基修饰提供了作为拮抗剂的中等效力，而N6-丙基完全消除了激动剂和拮抗剂特性。

  DOI：

  10.1021/jm970433l
• 作为产物：
  描述：

  2,6-双(甲基硫代)-9H-嘌呤 在 氨 、 sodium hydride 作用下， 反应 21.5h， 生成 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-6-methylsulfanyl-1H-pyrazolo[3,4-d]pyrimidine
  参考文献：
  名称：

  Synthesis and cytotoxicity of deoxyadenosine analogs: isomer distribution in the sodium salt glycosylation of 2,6-disubstituted purines

  摘要：

  Several 2-substituted deoxyadenosine derivatives were synthesized and screened for cytotoxicity toward hematopoietic cells in culture. To prepare intermediates for these syntheses, the sodium salts of 2,6-dibromopurine and 2,6-bis(methylthio)purine were reacted with 1-chloro-3,5-di-p-toluyl-alpha-D-erythro-pentofuranose in acetonitrile. Similar reactions using 6-chloropurines have been reported to give only 9-beta and 7-beta nucleosides as major and minor products, respectively. 2,6-Dibromopurine, however, gave 9-beta and 9-alpha isomers as major and minor products, along with a lesser amount of the 7-beta isomer. 2,6-Bis(methylthio)purine, in contrast, produced 9-beta and 7-beta isomers as major and minor products. These results are discussed in terms of sugar anomerization and possible steric and kinetic effects of base substituents in the sodium salt glycosylation reaction. Reactions of the 9-beta nucleoside isomers with ammonia and alkylamines produced several 2-bromo, 2-methylthio, and 2-amino deoxyadenosines. All of the compounds showed weaker cytotoxic activity than 2-bromodeoxyadenosine against hematopoietic cells in culture, when [14C]leucine incorporation into cellular proteins was measured.

  DOI：

  10.1021/jm00168a023

文献信息

• Synthesis of 2-Deoxy-β-D-ribonucleosides and 2,3-Dideoxy-β-D-pentofuranosides on Immobilized Bacterial Cells
  作者：Ivan Votruba、Antonín Holý、Hana Dvořáková、Jaroslav Günter、Dana Hocková、Hubert Hřebabecký、Tomas Cihlar、Milena Masojídková

  DOI：10.1135/cccc19942303

  日期：——

  Alginate gel-entrapped cells of auxotrophic thymine-dependent strain of E. coli catalyze the transfer of 2-deoxy-D-ribofuranosyl moiety of 2'-deoxyuridine to purine and pyrimidine bases as well as their aza and deaza analogs. All experiments invariably gave β-anomers; in most cases, the reaction was regiospecific, affording N⁹-isomers in the purine and N¹-isomers in the pyrimidine series. Also a 2,3-dideoxynucleoside can serve as donor of the glycosyl moiety. The acceptor activity of purine bases depends only little on substitution, the only condition being the presence of N⁷-nitrogen atom. On the other hand, in the pyrimidine series the activity is limited to only a narrow choice of mostly short 5-alkyl and 5-halogeno uracil derivatives. Heterocyclic bases containing amino groups are deaminated; this can be avoided by conversion of the base to the corresponding N-dimethylaminomethylene derivative which is then ammonolyzed. The method was verified by isolation of 9-(2-deoxy-β-D-ribofuranosyl) derivatives of adenine, guanine, 2-chloroadenine, 6-methylpurine, 8-azaadenine, 8-azaguanine, 1-deazaadenine, 3-deazaadenine, 1-(2-deoxy-β-D-ribofuranosyl) derivatives of 5-ethyluracil, 5-fluorouracil, and 9-(2,3-dideoxy-β-D-pentofuranosyl)hypoxanthine, 9-(2,3-dideoxy-β-D-pentofuranosyl)-6-methylpurine, and other nucleosides.

  藻酸盐凝胶包埋的辅助胸腺嘧啶依赖菌株大肠杆菌细胞催化2'-脱氧尿嘧啶的2-脱氧-D-核糖呋喃基团转移到嘌呤和嘧啶碱基以及它们的氮杂和去氮类似物。所有实验都不可避免地产生β-异构体；在大多数情况下，反应是区域特异性的，产生嘌呤中的N⁹-异构体和嘧啶系列中的N¹-异构体。此外，2,3-二脱氧核苷酸可以作为糖基团的供体。嘌呤碱基的受体活性仅在取代上有少许影响，唯一的条件是存在N⁷-氮原子。另一方面，在嘧啶系列中，活性仅限于大多数短链5-烷基和5-卤代尿嘧啶衍生物的狭窄选择。含氨基的杂环碱基会发生脱氨作用；可以通过将碱基转化为相应的N-二甲氨基甲烯基衍生物来避免这种情况，然后进行氨解作用。该方法通过分离腺嘌呤、鸟嘌呤、2-氯腺嘌呤、6-甲基嘌呤、8-氮杂腺嘌呤、8-氮杂鸟嘌呤、1-去氮腺嘌呤、3-去氮腺嘌呤的9-(2-脱氧-β-D-核糖呋喃基)衍生物，5-乙基尿嘧啶、5-氟尿嘧啶的1-(2-脱氧-β-D-核糖呋喃基)衍生物，以及9-(2,3-二脱氧-β-D-戊呋喃基)缺氧嘌呤、9-(2,3-二脱氧-β-D-戊呋喃基)-6-甲基嘌呤和其他核苷酸的验证。
• Structure−Activity Relationships of Bisphosphate Nucleotide Derivatives as P2Y₁ Receptor Antagonists and Partial Agonists
  作者：Erathodiyil Nandanan、Emidio Camaioni、Soo-Yeon Jang、Yong-Chul Kim、Gloria Cristalli、Piet Herdewijn、John A. Secrist、Kamal N. Tiwari、Arvind Mohanram、T. Kendall Harden、José L. Boyer、Kenneth A. Jacobson

  DOI：10.1021/jm980657j

  日期：1999.5.1

  anhydrohexitol ring modifications have been prepared and resulted in enhanced agonist properties. The 1,5-anhydrohexitol analogue 36 was a pure agonist with an EC50 of 3 microM, i.e., similar in potency to ATP. 5'-Phosphate groups have been modified in the form of triphosphate, methyl phosphate, and cyclic 3',5'-diphosphate derivatives. The carbocyclic analogue had enhanced agonist efficacy, and the 5'-O-phosphonylmethyl

  P2Y1 受体存在于心脏、骨骼和各种平滑肌以及血小板中，其激活与聚集有关。腺苷 3',5'- 和 2',5'-二磷酸已被鉴定为 P2Y1 受体的选择性拮抗剂 (Boyer et al. Mol. Pharmacol. 1996, 50, 1323-1329)，并已进行结构修饰以增加受体亲和力（Camaioni 等 J. Med. Chem. 1998, 41, 183-190）。我们将结构-活性关系扩展到一系列新的脱氧腺苷二磷酸，并在腺嘌呤碱基、核糖部分和磷酸基团中进行了取代。通过测量其刺激火鸡红细胞膜中磷脂酶 C（激动剂作用）和抑制 10 nM 2-（甲硫基）腺苷 5'-二磷酸引起的磷脂酶 C 刺激（拮抗剂作用）的能力，确定每种类似物对 P2Y1 受体的活性。 。在腺嘌呤环的 2 位上含有卤素、氨基和硫醚基团的 2'-脱氧腺苷二磷酸类似物是比在 8 位上含有各种杂原子取代的类似物更有效的
• Ligand-Enabled Copper-Catalyzed N6-Arylation of 2′-deoxyadenosine and its analogues
  作者：Yuhua Ge、Weifan Yuan、Ruoqian Xie、Raghunath Bag、Yutong Zhou、Yujie Jiang、Madiha Butt、Gang Chen

  DOI：10.1016/j.tetlet.2024.154983

  日期：2024.3

  [Display omitted]

  [显示省略]
• KAZIMIERCZUK, ZYGMUNT;VILPO, JUHANI;HILDEBRAND, CATHERINE;WRIGHT, GEORGE, J. MED. CHEM., 33,(1990) N, C. 1683-1687
  作者：KAZIMIERCZUK, ZYGMUNT、VILPO, JUHANI、HILDEBRAND, CATHERINE、WRIGHT, GEORGE

  DOI：——

  日期：——
• HOLY, A.;VOTRUBA, I., 7TH SYMP. CHEM. NUCL. ACID COMPON., BECHYNE CASTLE, AUG. 30TH - SEPT. 5TH+
  作者：HOLY, A.、VOTRUBA, I.

  DOI：——

  日期：——