8-bromo-9-methylguanine | 74427-56-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: 8-bromo-9-methylguanine
• 英文别名: 8-Bromo-9-methylguanine；2-amino-8-bromo-9-methyl-1H-purin-6-one
• CAS: 74427-56-8
• 化学式: C₆H₆BrN₅O
• 分子量: 244.051
• InChiKey: ZGVRBUQBBXTTIB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.1
• 重原子数：
  13
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  85.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  8-bromo-9-methylguanine 在 硫脲 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 4.0h， 生成 2-amino-8-[(4-fluorophenyl)methylsulfanyl]-9-methyl-1H-purin-6-one
  参考文献：
  名称：

  [EN] HETEROCYCLIC GTP CYCLOHYDROLASE 1 INHIBITORS FOR THE TREATMENT OF PAIN
  [FR] INHIBITEURS HÉTÉROCYCLIQUES DE LA GTP CYCLOHYDROLASE 1 POUR LE TRAITEMENT DE LA DOULEUR

  摘要：

  本发明涉及小分子杂环抑制剂对GTP环化酶（GCH-I）的，或其互变异构体、前药或药用可接受盐。该发明还涉及这些化合物的药物组合物以及这些化合物用于治疗或预防疼痛（例如炎症性疼痛、伤害性疼痛、功能性疼痛或神经病理性疼痛）的医疗用途。

  公开号：

  WO2011035009A1
• 作为产物：
  描述：

  8-溴鸟苷 生成 8-bromo-9-methylguanine
  参考文献：
  名称：

  STILLWELL, W. G.;XU, HOU-XIAO;ADKINS, JERROLD A.;WISHNOK, JOHN S.;TANNENB+, CHEM. RES. TOXICOL., 2,(1989) N, C. 94-99

  摘要：

  DOI：

文献信息

• 8-Mercaptoguanine Derivatives as Inhibitors of Dihydropteroate Synthase
  作者：Matthew L. Dennis、Michael D. Lee、Jitendra R. Harjani、Mohamed Ahmed、Aaron J. DeBono、Noel P. Pitcher、Zhong-Chang Wang、Sandeep Chhabra、Nicholas Barlow、Raphaël Rahmani、Ben Cleary、Olan Dolezal、Meghan Hattarki、Luigi Aurelio、Jeremy Shonberg、Bim Graham、Thomas S. Peat、Jonathan B. Baell、James D. Swarbrick

  DOI：10.1002/chem.201704730

  日期：2018.2.6

  Dihydropteroate synthase (DHPS) is an enzyme of the folate biosynthesis pathway, which catalyzes the formation of 7,8‐dihydropteroate (DHPt) from 6‐hydroxymethyl‐7,8‐dihydropterin pyrophosphate (DHPPP) and para‐aminobenzoic acid (pABA). DHPS is the long‐standing target of the sulfonamide class of antibiotics that compete with pABA. In the wake of sulfa drug resistance, targeting the structurally rigid

  二氢蝶呤合酶（DHPS）是叶酸生物合成途径中的一种酶，可催化6-羟甲基-7,8-二氢蝶呤焦磷酸（DHPPP）和对氨基苯甲酸（pABA）形成7,8-二氢蝶呤（DHPt）。DHPS是与pABA竞争的磺胺类抗生素的长期目标。在对磺胺类药物产生抗药性之后，已经提出了针对结构刚性（且更保守）的蝶呤位点作为抑制野生型和磺胺类药物耐药菌株中DHPS的替代策略。在开发相邻酶6-羟甲基-7,8-二氢蝶呤焦磷酸激酶（HPPK）的蝶呤位点抑制剂后，我们现在提供8-巯基鸟嘌呤的衍生物，该片段在两种酶中均弱结合，并定量亚μ米使用表面等离振子共振（SPR）结合大肠杆菌DHPS（EcDHPS）。十一个与配体结合的EcDHPS晶体结构描绘了观察到的结构-活性关系，为合理开发新型的，与底物-信封相容的DHPS抑制剂提供了结构框架。
• Bicyclic Compounds and Their Use
  申请人：Fairlamb Ian

  公开号：US20090299049A1

  公开（公告）日：2009-12-03

  The present invention provides fluorescent bicyclic compounds of the formula (I); wherein ring A, the broken lines -----, C 1 ----C 2 , R 4 and R 1 are as defined herein. The invention also relates to nucleoside and nucleotide analogues of said compounds, and their use as biological markers.

  本发明提供了式(I)的荧光双环化合物，其中环A，断裂的线-----，C1----C2，R4和R1如本文所定义。本发明还涉及该化合物的核苷和核苷酸类似物，以及它们作为生物标记物的用途。
• The discovery of purine-based agents targeting triple-negative breast cancer and the αB-crystallin/VEGF protein–protein interaction
  作者：Nelly A. Fosu-Mensah、Wen Jiang、Andrea Brancale、Jun Cai、Andrew D. Westwell

  DOI：10.1007/s00044-018-2275-9

  日期：2019.2

  Oestrogen receptor-negative breast cancer, particularly subtypes such as triple-negative breast cancer (TNBC, around 10-15% of cases), are characterised by poor long-term survival, poor response to therapy and early progression to metastasis. Purine-based compounds represent a privileged scaffold in anticancer drug design, with several clinically approved and experimental agents in clinical development comprising a purine core structure. In this study, a series of new purine-based compounds were synthesised; seven of the new analogues were found to significantly reduce the in vitro viability of TNBC cell lines (MDA-MB-231 and MDA-MB-436) with IC50 values of 50M. In previous work, we have proposed a new concept for targeting angiogenesis driving TNBC progression, by disrupting the protein-protein interaction between the molecular chaperone B-crystallin (CRYAB) and VEGF. Since previous clinical studies applying anti-VEGF therapy to TNBC patients have met with limited success, we were interested to test our most promising purine analogues against CRYAB/VEGF, using a custom-designed cell-based CRYAB/VEGF(165) interaction assay platform. Analogues 4e and 4f significantly reduced the interaction between CRYAB/VEGF(165), and compound 4e (100M) was also found to decrease the levels of soluble VEGF expressed by MDA-MB-231 cells by 40%. In conclusion, these promising early activity profiles warrant further investigation to validate this concept.
• STILLWELL, W. G.;XU, HOU-XIAO;ADKINS, JERROLD A.;WISHNOK, JOHN S.;TANNENB+, CHEM. RES. TOXICOL., 2,(1989) N, C. 94-99
  作者：STILLWELL, W. G.、XU, HOU-XIAO、ADKINS, JERROLD A.、WISHNOK, JOHN S.、TANNENB+

  DOI：——

  日期：——
• SUBSTITUTED O6 -BENZYLGUANINES AND 6(4)-BENZYLOXYPYRIMIDINES
  申请人：THE UNITED STATES OF AMERICA, as represented by the Secretary of the Department of Health and Human Services

  公开号：EP0775142A1

  公开（公告）日：1997-05-28