2,6-双(甲基硫代)-9H-嘌呤 | 1201-58-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 中文名称: 2,6-双(甲基硫代)-9H-嘌呤
• 英文名称: 2,6-bis(methylthio)purine
• 英文别名: 2,6-Bis-methylmercapto-purin；1H-Purine, 2,6-bis(methylthio)-；2,6-bis(methylsulfanyl)-7H-purine
• CAS: 1201-58-7
• 化学式: C₇H₈N₄S₂
• 分子量: 212.299
• InChiKey: QLBHIPFBFNPVKW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  105
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  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
• 作为产物：
  描述：

  2-Methylthio-6-thioxo-7.9-dimethylpurinium-jodid 生成 2,6-双(甲基硫代)-9H-嘌呤
  参考文献：
  名称：

  MURAVICH-ALEKSANDR X. L.; FRANKOVSKAYA I. V.; MEZHONOVA S. S., ZH. ORGAN. XIMII, 1978, 14, HO 8, 1744-1751

  摘要：

  DOI：

文献信息

• Kinetics of the Reaction of a Potential Chemopreventive Agent, 2,6-Dithiopurine, and Its Major Metabolite, 2,6-Dithiouric Acid, with Multiple Classes of Electrophilic Toxicants
  作者：Wei-Guo Qing、K. Leslie Powell、Michael C. MacLeod

  DOI：10.1021/tx960088n

  日期：1996.1.1

  exhibit nucleophilic scavenging activity against the carcinogenic electrophile benzo[a]pyrene diol epoxide (BPDE). Of the purinethiols tested previously, 2,6-dithiopurine (DTP), exhibited the highest scavenging activity for BPDE when tested either in vitro or in vivo. Sulfur-based nucleophiles are typically classified as "soft" nucleophiles, showing selectivity in nucleophilic substitution reactions

  嘌呤硫醇是一类潜在的癌症化学预防剂，对致癌的亲电子体苯并[a] py二醇环氧（BPDE）具有亲核清除活性。在先前测试的嘌呤硫醇中，无论是在体外还是在体内测试，2,6-二硫代嘌呤（DTP）对BPDE的清除能力最高。基于硫的亲核试剂通常被分类为“软”亲核试剂，显示出对“软”易极化的亲电子试剂的亲核取代反应的选择性。确定除BPDE以外的亲电子毒物是否能与DTP轻松反应，以及DTP的主要体内代谢物2,6-二硫代尿酸（DUA）是否也具有清除活性，是令人感兴趣的。在本工作中测试了四种不同的有毒物质，丙烯醛，美法仑，硫酸二甲酯和顺铂，在接近中性pH的条件下，所有这些试剂都能与DTP轻松反应。预期这些有毒物质会以“软”亲电试剂的形式发生反应。此外，这些化合物以及BPDE与DUA的反应速率常数可与与DTP反应的类似速率常数相媲美。相反，几种被分类为“硬”亲电试剂的毒物（甲磺酸乙酯，甲基亚硝基脲，乙基亚硝基脲
• Synthesis of 9-(2-fluorobenzyl)-6-methylamino-9<i>H</i>-purine
  作者：James L. Kelley、Ed W. McLean

  DOI：10.1002/jhet.5570230445

  日期：1986.7

  Synthesis of 9-(2-fluorobenzyl)-6-methylamino-9H-purine (1) from nine different precursors is reported. Compound 1 was prepared by methylamination of 6-chloro-9-(2-fluorobenzyl)-9H-purine (4), by alkylation of 6-methylaminepurine (5) or form 9-(2-fluorobenzyl)-1-methyladeninium iodide (8) via the Dimroth rearrangement. Selective 2-step methylation of 6-aminopurine 6 was accomplished by hydride reduction

  据报道由九种不同的前体合成9-（2-氟苄基）-6-甲基氨基-9 H-嘌呤（1）。化合物1的制备是通过将6-氯-9-（2-氟苄基）-9-甲氨基化ħ嘌呤（4）中，由6- methylaminepurine（烷基化5）或形式9-（2-氟苄基）-1- methyladeninium碘化（8）通过Dimroth重排。6-氨基嘌呤的选择性两步骤甲基化6用氢化物还原的6- formamidopurine完成9，6-dimethylaminomethyleneaminopurine 10或6-苯硫基嘌呤11，得到1化合物1也通过dethiation或2-甲硫基嘌呤的还原脱氯制备16或8氯嘌呤19，分别，或由6-水解Ñ -methylformamidopurine 12，将其从6-二甲基氨基制备13通过选择性氧化。
• An alternative to ‘propylene/Leonard linker’ for studying arene interactions in flexible pyrazolo[3,4-d]pyrimidine core based models both at molecular and supramolecular levels
  作者：Kamlakar Avasthi、Amantullah Ansari、Ruchir Kant、Prakas R. Maulik、Krishnan Ravikumar、Partha Chattopadhyay、Nirmal D. Adhikary

  DOI：10.1039/c0ce00336k

  日期：——

  An alternative C-3 linker to ‘propylene/Leonard linker’ is proposed for studying arene interactions in face-to-face (offset) mode. The two new flexible symmetrical compounds with an electron deficient pyrazolo[3,4-d]pyrimidine core and biologically important isomeric purine systems and one dissymmetrical compound with a pyrazolo[3,4-d]pyrimidine core and electron-rich carbazole residue at the termini of the new linker show folding due to intramolecular π–π interactions by both 1H NMR in solution and X-ray crystallography in the solid state. Surprisingly, the replacement of the 4-methylsulfanyl group of the dissymmetrical compound by an electron donating methoxy group shows open conformation in the solid state by X-ray crystallography. The fifth symmetrical compound with an electron-rich carbazole residue at the termini of new linker, however, shows the normally expected open conformation.

  为研究面对面（偏移）模式下的炔类相互作用，提出了一种替代 "丙烯/莱昂纳德连接体 "的 C-3 连接体。通过溶液中的 1H NMR 和固态中的 X 射线晶体学分析，两个以缺电子的吡唑并[3,4-d]嘧啶为核心、具有重要生物学意义的异构嘌呤系统的新型柔性对称化合物，以及一个以吡唑并[3,4-d]嘧啶为核心、在新连接体末端具有富电子咔唑残基的不对称化合物，都显示出分子内ÏâÏ相互作用导致的折叠。令人惊讶的是，通过 X 射线晶体学研究，用一个电子捐赠的甲氧基取代不对称化合物中的 4-甲硫基，在固态下显示出开放构象。第五种对称化合物在新连接体的末端含有一个富电子咔唑残基，但却显示出正常预期的开放构象。
• Folded conformations due to arene interactions in dissymmetric and symmetric butylidene-linker models based on pyrazolo[3,4-<i>d</i>]pyrimidine, purine and 7-deazapurine
  作者：Kamlakar Avasthi、Lakshmi Shukla、Ruchir Kant、Krishnan Ravikumar

  DOI：10.1107/s2053229614009449

  日期：2014.6.15

  models 1‐[2‐(2,6‐dimethylsulfanyl‐9H‐purin‐9‐yl)‐2‐methylidenepropyl]‐4,6‐bis(methylsulfanyl)‐1H‐pyrazolo[3,4‐d]pyrimidine, C18H20N8S4, (XI), 7,7′‐(2‐methylidenepropane‐1,3‐diyl)bis[3‐methyl‐2‐methylsulfanyl‐3H‐pyrrolo[2,3‐d]pyrimidin‐4(7H)‐one], C20H22N6O2S2, (XIV), and 7‐[2‐(4,6‐dimethylsulfanyl‐1H‐pyrazolo[3,4‐d]pyrimidin‐1‐yl)‐2‐methylidenepropyl]‐3‐methyl‐2‐methylsulfanyl‐3H‐pyrrolo[2,3‐d]pyrimidin‐4(7H)‐one

  丁叉接头模型1 [[2-（2,6-二甲基硫烷基-9 H-嘌呤-9-9基）-2-亚甲基丙基] -4,6-双（甲基硫烷基）-1 H-吡唑并[3,4- d ]嘧啶，C 18 H 20 N 8 S 4，（XI），7,7'-（2-亚甲基丙烷-1,3-二基）双[3-甲基-2-甲基硫基-3 H-吡咯并[2， 3 - d ]嘧啶-4（7 H）-1 ]，C 20 H 22 N 6 O 2 S 2，（XIV）和7- [2-（4,6-二甲基硫烷基-1 H-吡唑并[3， 4 - d ]嘧啶-1-基）-2-亚甲基丙基] -3-甲基-2-甲基硫烷基-3H-吡咯并[2,3 - d ]嘧啶-4（7 H）-one，C 19 H 21 N 7 OS 3（XV）在溶液中显示折叠构象，如1 H NMR分析所示。这种折叠会延续到结晶状态。在所有三种化合物中均观察到分子内π-π相互作用，但只有（XIV）在固态下显示出额外的分子内CH-H
• INHIBITORS OF HUMAN PHOSPHATIDYLINOSITOL 3-KINASE DELTA
  申请人：Sadhu Chanchal

  公开号：US20120172591A1

  公开（公告）日：2012-07-05

  Methods of inhibiting phosphatidylinositol 3-kinase delta isoform (PI3Kδ) activity, and methods of treating diseases, such as disorders of immunity and inflammation, in which PI3Kδ plays a role in leukocyte function are disclosed. Preferably, the methods employ active agents that selectively inhibit PI3Kδ, while not significantly inhibiting activity of other PI3K isoforms. Compounds are provided that inhibit PI3Kδ activity, including compounds that selectively inhibit PI3Kδ activity. Methods of using PI3Kδ inhibitory compounds to inhibit cancer cell growth or proliferation are also provided. Accordingly, the invention provides methods of using PI3Kδ inhibitory compounds to inhibit PI3Kδ-mediated processes in vitro and in vivo.

  本发明揭示了抑制磷脂酰肌醇3-激酶δ亚型（PI3Kδ）活性的方法，以及治疗免疫和炎症等疾病的方法，其中PI3Kδ在白细胞功能中发挥作用。优选地，这些方法采用能够选择性地抑制PI3Kδ而不显著抑制其他PI3K亚型活性的活性剂。提供了抑制PI3Kδ活性的化合物，包括选择性抑制PI3Kδ活性的化合物。还提供了使用PI3Kδ抑制剂化合物抑制癌细胞生长或增殖的方法。因此，本发明提供了使用PI3Kδ抑制剂化合物在体外和体内抑制PI3Kδ介导的过程的方法。