6-硫代-7,9-二氢-3H-嘌呤-8-酮 | 20917-46-8

• 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: 6-硫代-7,9-二氢-3H-嘌呤-8-酮
• 英文名称: 6-Thioxopurin-8-on
• 英文别名: 6-Mercapto-8-hydroxypurin；8-Hydroxy-purin-thion-(6)；6-thioxo-1,6,7,9-tetrahydro-purin-8-one；6-Thioxo-1,6,7,9-tetrahydro-purin-8-on；1,6,7,9-tetrahydro-6-thioxo-8H-purin-8-one；6-sulfanylidene-7,9-dihydro-3H-purin-8-one
• CAS: 20917-46-8
• 化学式: C₅H₄N₄OS
• 分子量: 168.179
• InChiKey: OIZCDCVIFRRJFF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.1
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  97.6
• 氢给体数：
  3
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  6-硫代-7,9-二氢-3H-嘌呤-8-酮 在 氢氧化钾 、 三氯氧磷 作用下， 生成 8-chloro-6-methylsulfanyl-7(9)H-purine
  参考文献：
  名称：

  Potential Purine Antagonists. XV. Preparation of Some 6,8-Disubstituted Purines¹

  摘要：

  DOI：

  10.1021/ja01557a051
• 作为产物：
  描述：

  7H-嘌呤-6,8-二醇 在 吡啶 、 tetraphosphorus decasulfide 作用下， 生成 6-硫代-7,9-二氢-3H-嘌呤-8-酮
  参考文献：
  名称：

  Potential Purine Antagonists. XV. Preparation of Some 6,8-Disubstituted Purines¹

  摘要：

  DOI：

  10.1021/ja01557a051

文献信息

• Inhibition of UDP-glucose dehydrogenase by 6-thiopurine and its oxidative metabolites: Possible mechanism for its interaction within the bilirubin excretion pathway and 6TP associated liver toxicity
  作者：Chamitha J. Weeramange、Cassie M. Binns、Chixiang Chen、Ryan J. Rafferty

  DOI：10.1016/j.jpba.2017.12.058

  日期：2018.3

  fully oxidized at carbon 2 and 8, and highly retained by the body) has a near six-fold increased inhibition towards UDPGDH with a Ki of 7 μM. Inhibition was also observed by 6-thioxanthine (oxidized at carbon 2) and 8-OH-6TP with Ki values of 54 and 14 μM, respectively. Neither 6-thiopurine or its excretion metabolites were shown to inhibit UGT1A1. Our results show that the C2 and C8 positions of 6TP

  6-硫嘌呤（6TP）是一种治疗各种疾病的积极处方药，从克罗恩氏病和其他炎性疾病到急性淋巴细胞性白血病和非霍奇金氏白血病，不一而足。尽管6TP具有有益的治疗用途，但据报道其使用也会产生严重的毒性，例如黄疸和肝毒性。尽管已经对毒性产生的方式进行了大量研究。没有人研究抑制对UDP-葡萄糖脱氢酶（UDPGDH）的抑制作用，UDPGDH是负责UDP-葡萄糖醛酸（UDPGA）形成的氧化酶或UDP-葡萄糖醛酸转移酶（UGT1A1），后者负责将胆红素与UDPGA结合排泄。 。未能排出胆红素会导致黄疸和肝毒性。我们建议6TP或其主要的氧化排泄代谢产物抑制这些酶中的一种或两种，从而导致从6TP给药中观察到的毒性。对这些嘌呤的抑制分析表明，6-硫嘌呤对带有K的UDPGDH具有弱至无抑制作用我288μM的关于变化的UDP-葡萄糖，但6- thiouric（初级端代谢物，在碳2和8完全氧化，和由所述主体高度保留的）
• Condensed Pyrimidine Systems. XX. Purines Related to 6-Mercaptopurine and Thioguanine
  作者：Gertrude B. Elion、Irving Goodman、William Lange、George H. Hitchings

  DOI：10.1021/ja01517a030

  日期：1959.4
• Rational Design of Novel Immunosuppressive Drugs:  Analogues of Azathioprine Lacking the 6-Mercaptopurine Substituent Retain or Have Enhanced Immunosuppressive Effects
  作者：Duncan J. K. Crawford、John L. Maddocks、D. Neville Jones、Paul Szawlowski

  DOI：10.1021/jm960132w

  日期：1996.1.1

  Clinical use of the immunosuppressive drug azathioprine is limited by potentially serious toxic effects related to depression of bone marrow function. The immunosuppressive and toxic properties of azathioprine are regarded as being properties of the cytotoxicity of its metabolite, 6-mercaptopurine (6-MP). However, azathioprine has an immunosuppressive effect additional to that attributable to 6-MP alone, and we propose that this is associated with an action of the methylnitroimidazolyl substituent. This suggests a route to the rational design of nontoxic immunosuppressants by replacing the 6-MP component of azathioprine with nontoxic thiols. We have synthesized and tested in vitro 24 such analogues, with two being further tested in vivo. In the human mixed lymphocyte reaction, virtually all compounds showed some degree of activity, 10 compounds being more active than azathioprine. In vivo, two compounds were more effective than azathioprine at prolonging graft survival in mice. In an oral toxicity study in male CD1 mice at doses equivalent to those at which azathioprine caused severe bone marrow depression both analogues had no toxic effects. Our results show that the immunosuppressive effects and bone marrow toxicity of azathioprine are not a consequence of release of 6-MP alone, and with appropriate modification can be separated, an approach which may lead to less toxic immunosuppressive drugs.