GP683 | 144928-17-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: GP683
• 英文别名: 2-Methyl-5-(5-phenyl-4-phenylamino-pyrrolo[2,3-d]pyrimidin-7-yl)-tetrahydro-furan-3,4-diol；(2R,3R,4S,5R)-2-(4-anilino-5-phenylpyrrolo[2,3-d]pyrimidin-7-yl)-5-methyloxolane-3,4-diol
• CAS: 144928-17-6
• 化学式: C₂₃H₂₂N₄O₃
• 分子量: 402.453
• InChiKey: YPWISWJHVQIXIL-DVHMWJAFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  92.4
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-乙酰氧基异丁酰溴 、 GP683 在 水 作用下， 以 乙腈 为溶剂， 反应 0.67h， 以63%的产率得到4-N-phenylamino-5-phenyl-7-(2-O-acetoxy-3β-bromo-3,5-dideoxy-β-D-ribofuranosyl)pyrrolo[2,3-d]pyrimidine
  参考文献：
  名称：

  Adenosine Kinase Inhibitors. 2. Synthesis, Enzyme Inhibition, and Antiseizure Activity of Diaryltubercidin Analogues

  摘要：

  In the preceding article (Ugarkar et al. J. Med. Chem. 2000, 43) we reported that analogues of tubercidin are potent adenosine kinase (AK) inhibitors with antiseizure activity in the rat maximum electroshock (MES) model. Despite the discovery of several highly potent AK inhibitors (AKIs), e.g., 5'-amino-5'-deoxy-5-iodotubercidin (1c) (IC50 = 0.0006 mu M), no compounds were identified that exhibited a safety, efficacy, and side effect profile suitable for further development. In this article, we demonstrate that substitution of the tubercidin molecule with aromatic rings at the N4- and the C5-positions not only retains AKI potency but also improves in vivo activity. Synthesis of such compounds entailed transformation of 4-arylanlino-5-iodotubercidin analogues to their corresponding 5-aryl derivatives via the Suzuki reaction. Alternatively, 4-N-suylamino-5-arylpyrrolo[2,3-d]pyrimdine bases were constructed and then glycosylated with appropriately protected alpha-ribofuranosyl chlorides using a phase-transfer catalyst. Several compounds exhibited potent activity in the rat MES seizure assay with ED(50)s less than or equal to 2.0 mg/kg, ip, and showed relatively mild side effects.

  DOI：

  10.1021/jm0000259
• 作为产物：
  描述：

  4-氯-5-碘-7H-吡咯并[2,3-d]嘧啶 在 四(三苯基膦)钯 、 sodium acetate 、 sodium hydride 、 sodium carbonate 、 三氟乙酸 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 16.0h， 生成 GP683
  参考文献：
  名称：

  Design, Synthesis and Anticonvulsant Activity of the Potent Adenosine Kinase Inhibitor GP3269

  摘要：

  The pyrrolopyrimidine nucleoside GP3269 (12) was shown to be a potent and selective inhibitor of human adenosine kinase (IC50 = 11 nM) and to exhibit anticonvulsant activity in rats after oral administration. Synthesis of GP3269 was accomplished in 4 steps from 4-chloro-5-iodopyrrolopyrimidine (9) and the protected 5-deoxy-1-alpha-chlororibose (8) using a base-catalyzed nucleoside coupling reaction and the Suzuki reaction to replace the 5-iodo substituent with phenyl.

  DOI：

  10.1080/07328319708006124

文献信息

• [EN] ADENOSINE KINASE INHIBITORS
  申请人：GENSIA, INC.

  公开号：WO1992012718A1

  公开（公告）日：1992-08-06

  (EN) Novel compounds which selectively inhibit adenosine kinase and methods of preparing adenosine kinase inhibitors are provided. Also provided are methods of treating various conditions which may be ameliorated by increased local concentrations of adenosine using adenosine kinase inhibitors.(FR) L'invention se rapporte à de nouveaux composés qui possèdent un pouvoir inhibiteur sélectif sur l'adénosine-kinase, ainsi qu'à des procédés de préparation d'agents inhibiteurs de l'adénosine-kinase. Sont également décrits des procédés qui servent à traiter divers états dont on peut obtenir une amélioration en augmentant les concentrations locales d'adénosine et qui utilisent à cet effet des agents inhibiteurs de l'adénosine-kinase.

  提供了一种新型化合物，可选择性地抑制腺苷激酶，并提供制备腺苷激酶抑制剂的方法。还提供了使用腺苷激酶抑制剂治疗可能通过增加局部腺苷浓度改善的各种情况的方法。
• Adenosine kinase inhibitors
  申请人：Metabasis Therapeutics Inc.

  公开号：EP0496617B1

  公开（公告）日：1999-12-01
• ORALLY ACTIVE ADENOSINE KINASE INHIBITORS
  申请人：GENSIA, INC.

  公开号：EP0832092A1

  公开（公告）日：1998-04-01
• PROCESS FOR PREPARING 5-ALKYL-7H-PYRROLO[2,3-D]PYRIMIDINE-2-OLS
  申请人：Lexicon Pharmaceuticals, Inc.

  公开号：EP2084130B1

  公开（公告）日：2012-06-27
• BETA-CELL REPLICATION PROMOTING COMPOUNDS AND METHODS OF THEIR USE
  申请人：President and Fellows of Harvard College

  公开号：EP2513298A2

  公开（公告）日：2012-10-24