8-(benzylthio)-1,3,7-trimethyl-1H-purine-2,6-(3H,7H)-dione | 24851-28-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-(benzylthio)-1,3,7-trimethyl-1H-purine-2,6-(3H,7H)-dione
• 英文别名: 8-(benzylthio)-1,3,7-trimethyl-1H-purine-2,6(3H,7H)-dione；1,3,7-trimethyl-8-(benzylthio)xanthine；8-benzylsulfanyl-1,3,7-trimethyl-3,7-dihydro-purine-2,6-dione；8-benzylmercapto-1,3,7-trimethyl-3,7-dihydro-purine-2,6-dione；8-Benzylmercapto-1,3,7-trimethyl-3,7-dihydro-purin-2,6-dion；8-Benzylthiocoffein；8-Benzylsulfanyl-1,3,7-trimethylpurine-2,6-dione
• CAS: 24851-28-3
• 化学式: C₁₅H₁₆N₄O₂S
• 分子量: 316.384
• InChiKey: LKHBCOZTKMDQEV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  22
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  83.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  8-(benzylthio)-1,3,7-trimethyl-1H-purine-2,6-(3H,7H)-dione 在 Oxone 作用下， 以 甲醇 、 水 为溶剂， 反应 5.0h， 以51.6%的产率得到8-(benzylsulfonyl)-1,3,7-trimethyl-3,7-dihydro-1H-purine-2,6-dione
  参考文献：
  名称：

  发现了一类针对混合谱系激酶结构域样蛋白的新型强效坏死抑制剂

  摘要：

  开发了一系列具有单纳摩尔效价的新型混合谱系激酶结构域类似蛋白（MLKL）抑制剂。

  DOI：

  10.1039/c7cc00667e
• 作为产物：
  描述：

  8-氯-3,7-二氢-1,3,7-三甲基-1H-嘌呤-2,6-二酮 在 sodium hydrogensulfide 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 生成 8-(benzylthio)-1,3,7-trimethyl-1H-purine-2,6-(3H,7H)-dione
  参考文献：
  名称：

  发现了一类针对混合谱系激酶结构域样蛋白的新型强效坏死抑制剂

  摘要：

  开发了一系列具有单纳摩尔效价的新型混合谱系激酶结构域类似蛋白（MLKL）抑制剂。

  DOI：

  10.1039/c7cc00667e

文献信息

• Two-step three-component process for one-pot synthesis of 8-alkylmercaptocaffeine derivatives
  作者：M. N. Soltani Rad、S. Maghsoudi

  DOI：10.1039/c6ra17814f

  日期：——

  A highly efficient, odourless and two-step three-component process for one-pot synthesis of some 8-alkylmercaptocaffeine derivatives has been described. The catalyst-free three-component reaction of alkyl bromides, thiourea, and 8-bromocaffeine gave 8-alkylmercaptocaffeine products in excellent to quantitative yields. In addition, the impact of parameters on sample reaction is discussed.

  已经描述了一种高效，无味，两步三组分法，用于一锅合成一些8-烷基巯基咖啡因衍生物。烷基溴，硫脲和8-溴咖啡因的无催化剂三组分反应以优异的定量收率得到了8-烷基巯基咖啡因产物。此外，还讨论了参数对样品反应的影响。
• 8-Alkylmercaptocaffeine derivatives: antioxidant, molecular docking, and in-vitro cytotoxicity studies
  作者：Saman Sargazi、Sheida Shahraki、Omolbanin Shahraki、Farshid Zargari、Roghayeh Sheervalilou、Saeid Maghsoudi、Mohammad Navid Soltani Rad、Ramin Saravani

  DOI：10.1016/j.bioorg.2021.104900

  日期：2021.6

  damage (P > 0.05). Computational studies showed that H-bond formation between the nitrogen atom in pyrazolo[4,3-D] pyrimidine moiety with Gln817 and creating a hydrophobic cavity result in the stability of the alkyl group in the PDE5A active site. We found that synthesized 8-alkylmercaptocaffeine derivatives induced cell death in different cancer cells through the cGMP pathway. These findings will help

  由于其独特的药理特性，甲基黄嘌呤被认为是具有广泛药用范围的治疗剂。在本报告中，我们旨在检查先前合成的 8-烷基巯基咖啡因衍生物的一些生物学效应。在恶性 A549、MCF7 和 C152 细胞系中测量了 8-烷基巯基咖啡因衍生物的细胞毒性和抗氧化活性。使用比色竞争 ELISA 试剂盒进行 cGMP 水平和 caspase-3 活性的评估。计算方法被用来发现合成化合物的抑制机制。在十二种合成的衍生物中，带有丙基、庚基和 3-甲基-丁基部分的三种化合物（C1、C5 和 C7）对所有研究的细胞系都显示出更高和更理想的细胞毒活性（IC50 < 100 µM）。此外，C5 在 MCF-7 细胞中协同增强顺铂诱导的细胞毒性（CI < 1）。在所有研究的细胞系中，C5 和 C7 在特定时间间隔显着增加 caspase-3 活性和细胞内 cGMP 水平（P < 0.05）。然而，这些衍生物并未增加LDH渗漏（P
• [EN] MLKL INHIBITORS<br/>[FR] INHIBITEURS MLKL
  申请人：NAT INSTITUTE OF BIOLOGICAL SCIENCES BEIJING

  公开号：WO2018157800A1

  公开（公告）日：2018-09-07

  Purine derivatives that inhibit cellular necroptosis and/or human MLKL, pharmaceutical compositions thereof, and methods of treating an MLKL-mediated disorder with an effective amount of the compound or composition. Said MLKL-mediated disorder is pathology associated necroptosis, including ischemia-reperfusion damage, neurodegeneration, and inflammatory diseases such as acute pancreatitis, multiple sclerosis, inflammatory bowel disease, and allergic colitis.

  嘌呤衍生物，用于抑制细胞坏死性凋亡和/或人类MLKL；包含该衍生物的药物组合物；以及使用有效量的该化合物或组合物治疗MLKL介导的疾病的方法。所述MLKL介导的疾病是与坏死性凋亡相关的病理学，包括缺血再灌注损伤、神经退行性疾病、以及诸如急性胰腺炎、多发性硬化症、炎症性肠病和过敏性结肠炎等炎症性疾病。
• Copper-catalyzed direct thiolation of xanthines and related heterocycles with disulfides
  作者：Zuying He、Fang Luo、Yinglong Li、Gangguo Zhu

  DOI：10.1016/j.tetlet.2013.08.097

  日期：2013.10

  A novel copper-catalyzed, base-free direct thiolation of xanthines and related heterocycles is described, featuring the use of inexpensive Cu(OAc)2·H2O as the catalyst, O2 as a clean and cheap oxidant, and easy-to-handle disulfides as the thiolation reagents. It works well for both aryl and alkyl disulfides. Moreover, the resultant products can be converted into 8-(hetero)aryl- or alkenyl-substituted

  描述了一种新颖的铜催化的黄嘌呤和相关杂环的无碱直接硫醇化反应，其特征在于使用廉价的Cu（OAc）2 ·H 2 O作为催化剂，O 2作为清洁廉价的氧化剂，并且易于使用-处理二硫化物作为硫醇化试剂。它对于芳基和烷基二硫化物均适用。此外，通过利伯斯金德-索罗尔偶联反应，可以高收率将所得产物转化为8-（杂）芳基或烯基取代的黄嘌呤。
• Inhibition of monoamine oxidase by 8-[(phenylethyl)sulfanyl]caffeine analogues
  作者：Samantha Mostert、Wayne Mentz、Anél Petzer、Jacobus J. Bergh、Jacobus P. Petzer

  DOI：10.1016/j.bmc.2012.10.005

  日期：2012.12

  In a previous study we have investigated the monoamine oxidase (MAO) inhibitory properties of a series of 8-sulfanylcaffeine analogues. Among the compounds studied, 8-[(phenylethyl) sulfanyl] caffeine (IC50 = 0.223 mu M) was found to be a particularly potent inhibitor of the type B MAO isoform. In an attempt to discover potent MAO inhibitors and to further examine the structure-activity relationships (SAR) of MAO inhibition by 8-sulfanylcaffeine analogues, in the present study a series of 8-[(phenylethyl)sulfanyl] caffeine analogues were synthesized and evaluated as inhibitors of human MAO-A and -B. The results document that substitution on C3 and C4 of the phenyl ring with alkyl groups and halogens yields 8-[( phenylethyl) sulfanyl] caffeine analogues which are potent and selective MAO-B inhibitors with IC50 values ranging from 0.017 to 0.125 mu M. The MAO inhibitory properties of a series of 8-sulfinylcaffeine analogues were also examined. The results show that, compared to the corresponding 8-sulfanylcaffeine analogues, the 8-sulfinylcaffeins are weaker MAO-B inhibitors. Both the 8-sulfanylcaffeine and 8-sulfinylcaffeine analogues were found to be weak MAO-A inhibitors. This study also reports the MAO inhibition properties of selected 8-[(phenylpropyl) sulfanyl] caffeine analogues. (C) 2012 Elsevier Ltd. All rights reserved.