2-氨基-9-(2-甲基丙基)-3H-嘌呤-6-酮 | 93692-99-0

• 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-氨基-9-(2-甲基丙基)-3H-嘌呤-6-酮
• 英文名称: 9-isobutylguanine
• 英文别名: 2-amino-9-isobutyl-1,9-dihydro-purin-6-one；2-Amino-9-isobutyl-1,9-dihydro-purin-6-on；2-amino-9-(2-methylpropyl)-3H-purin-6-one；2-amino-9-(2-methylpropyl)-1H-purin-6-one
• CAS: 93692-99-0
• 化学式: C₉H₁₃N₅O
• 分子量: 207.235
• InChiKey: DAYRGDIXHKHZQN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  85.3
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  2-氨基-9-(2-甲基丙基)-3H-嘌呤-6-酮 在 溴 作用下， 以 溶剂黄146 为溶剂， 反应 18.0h， 生成 2-Amino-8-bromo-9-isobutyl-9h-purin-6-ol
  参考文献：
  名称：

  The discovery of purine-based agents targeting triple-negative breast cancer and the αB-crystallin/VEGF protein–protein interaction

  摘要：

  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.

  DOI：

  10.1007/s00044-018-2275-9
• 作为产物：
  描述：

  2-氨基-6-氯嘌呤 在 盐酸 、 水 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.5h， 生成 2-氨基-9-(2-甲基丙基)-3H-嘌呤-6-酮
  参考文献：
  名称：

  The discovery of purine-based agents targeting triple-negative breast cancer and the αB-crystallin/VEGF protein–protein interaction

  摘要：

  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.

  DOI：

  10.1007/s00044-018-2275-9

文献信息

• Pyrazolylboratozinc Complexes of Nucleosides and Nucleoside Analogues
  作者：Dirk Badura、Heinrich Vahrenkamp

  DOI：10.1002/ejic.200300275

  日期：2003.10

  Attachment of deprotonated nucleosides or of alkylated nucleobases, as their analogues, to zinc was achieved by condensation reactions between TpZn-OH complexes and nucleobase derivatives. Pyrazolylboratozinc complexes with derivatives of uracil, thymine, guanine, xanthine and hypoxanthine were obtained and characterized by structure determination. In the uracil, thymine, guanine and hypoxanthine derivatives

  去质子化核苷或烷基化核碱基作为它们的类似物与锌的连接是通过 TpZn-OH 配合物和核碱基衍生物之间的缩合反应实现的。获得了吡唑基硼锌与尿嘧啶、胸腺嘧啶、鸟嘌呤、黄嘌呤和次黄嘌呤衍生物的配合物，并通过结构测定对其进行了表征。在尿嘧啶、胸腺嘧啶、鸟嘌呤和次黄嘌呤衍生物中，锌与核苷中带有质子的氮原子结合。在黄嘌呤衍生物中，实现了所有三种可能的键合模式。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)
• Cyclic dinucleotide
  申请人：TAKEDA PHARMACEUTICAL COMPANY LIMITED

  公开号：US10980825B2

  公开（公告）日：2021-04-20

  The present disclosure provides a compound having a STING agonistic activity, which may be expected to be useful as an agent for the prophylaxis or treatment of STING-related diseases. The present disclosure relates to a compound represented by the formula (I): wherein each symbol is as defined in the description, or a salt thereof.

  本公开提供了一种具有 STING 激动活性的化合物，该化合物有望用作预防或治疗 STING 相关疾病的药物。 本公开涉及一种由式（I）表示的化合物： 其中各符号如描述中所定义，或其盐类。
• Potential Purine Antagonists. XI. Synthesis of Some 9-Aryl(alkyl)-2,6-disubstituted Purines
  作者：Henry C. Koppel、Roland K. Robins

  DOI：10.1021/ja01544a044

  日期：1958.6
• Potential Purine Antagonists. XIX. Synthesis of Some 9-Alkyl(aryl)-2-amino-6-substituted Purines and Related V-Triazolo [d]pyrimidines¹
  作者：Henry C. Koppel、Darrell E. O'Brien、Roland K. Robins

  DOI：10.1021/ja01521a034

  日期：1959.6
• Pyrazolylborate−Zinc−Nucleobase-Complexes, 3:¹ Base Pairing Studies
  作者：Dirk Badura、Heinrich Vahrenkamp

  DOI：10.1021/ic020279f

  日期：2002.11.1

  In solution, the pyrazolylborate-zinc-nucleobase complexes show self-association and base pairing with external nucleobases. The self-association was studied quantitatively for Tp(Cum,Me)Zn-hypoxanthinate and Tp(Cum,Me)Zn-hypoxanthinate the dimerization constants K-D are 63 +/- 8 and 0.2 +/- 0.1 M-1, respectively. Of the external nucleobases, 9-ethyladenine forms stable base pairs with the thyminate, uracilate, and xanthinate complexes, 9-isobutylguanine only with the cytosinate complex, 1-methylthymine with the adeninate and diaminopurinate complexes, and 1-methyluracil with the diaminopurinate complex. The association constant for the base pair Tp(Cum,Me)Zn-thyminate:9-ethyladenine was determined by NMR methods as K = 66 +/- 10 M-1. Structure determinations of the crystalline adducts have confirmed the base pairing for Tp(Cum,Me)Zn-thyminate:9-ethyladenine, Tp(Cum,Me)Zn-cytosinate:9-isobutylguanine, and Tp(Cum,Me)Zn-xanthinate:9-ethyladenine. Both Watson-Crick and Hoogsteen base pairs have been observed. In the solid state, extended base pairing leads to quartet and polymer arrangements.