6-bromo-5-phenyl-4-N-phenylaminopyrrolo[2,3-d]pyrimidine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 6-bromo-5-phenyl-4-N-phenylaminopyrrolo[2,3-d]pyrimidine
• 英文别名: 6-bromo-N,5-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amine
• 化学式: C₁₈H₁₃BrN₄
• 分子量: 365.232
• InChiKey: FFBXIBLPCHNTDL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  53.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-bromo-5-phenyl-4-N-phenylaminopyrrolo[2,3-d]pyrimidine 在 氢氧化钾 作用下， 以 甲苯 为溶剂， 反应 0.75h， 生成 2-(6-Bromo-5-phenyl-4-phenylamino-pyrrolo[2,3-d]pyrimidin-7-yl)-5-methyl-tetrahydro-furan-3,4-diol
  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：

  2-氨基-3-氰基-4-苯基吡咯 在 N-溴代丁二酰亚胺(NBS) 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.75h， 生成 6-bromo-5-phenyl-4-N-phenylaminopyrrolo[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

文献信息

• Orally active adenosine kinase inhibitors
  申请人：Metabasis Therapeutics, Inc.

  公开号：US05763597A1

  公开（公告）日：1998-06-09

  This invention relates to adenosine kinase inhibitors and to nucleoside analogs, specifically to orally active, substituted 5-aryl pyrrolo\x9b2,3-d! pyrimidine and 3-aryl pyrazolo\x9b3,4-d! pyrimidine nucleoside analogs having activity as adenosine kinase inhibitors. The invention also relates to the preparation and use of these and other adenosine kinase inhibitors in the treatment of cardiovascular and cerebrovascular diseases, inflammation and other diseases which can be regulated by increasing the local concentration of adenosine.

  这项发明涉及腺苷激酶抑制剂和核苷类似物，具体涉及口服活性的取代5-芳基吡咯并[2,3-d]嘧啶和3-芳基吡唑并[3,4-d]嘧啶核苷类似物，其作为腺苷激酶抑制剂的活性。该发明还涉及这些和其他腺苷激酶抑制剂的制备和使用，用于治疗心血管和脑血管疾病、炎症和其他可以通过增加腺苷局部浓度来调节的疾病。
• ORALLY ACTIVE ADENOSINE KINASE INHIBITORS
  申请人：GENSIA, INC.

  公开号：EP0832092A1

  公开（公告）日：1998-04-01
• [EN] ORALLY ACTIVE ADENOSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS D'ADENOSINE KINASE ACTIFS ORALEMENT
  申请人：GENSIA-SICOR

  公开号：WO1996040706A1

  公开（公告）日：1996-12-19

  (EN) This invention relates to adenosine kinase inhibitors and to nucleoside analogs, specifically to orally active, substituted 5-aryl pyrrolo[2,3-d] pyrimidine and 3-aryl pyrazolo[3,4-d] pyrimidine nucleoside analogs having activity as adenosine kinase inhibitors. The invention also relates to the preparation and use of these and other adenosine kinase inhibitors in the treatment of cardiovascular and cerebrovascular diseases, inflammation and other diseases which can be regulated by increasing the local concentration of adenosine.(FR) L'invention concerne des inhibiteurs d'adénosine kinase et des analogues de nucléosides, et spécifiquement les analogues de nucléosides 5-aryl pyrrolo(2,3-d) pyrimidine et 3-aryl pyrazolo(3,4-d) substitués, oralement actifs, présentant une activité en tant qu'inhibiteurs d'adénosine kinase. L'invention concerne également la préparation et l'utilisation de ces inhibiteurs d'adénosine kinase et d'autres inhibiteurs pour le traitement de maladies cardiovasculaires et cérébrovasculaires, de maladies inflammatoires et d'autres maladies qu'on peut réguler en augmentant la concentration locale d'adénosine.
• Adenosine Kinase Inhibitors. 2. Synthesis, Enzyme Inhibition, and Antiseizure Activity of Diaryltubercidin Analogues
  作者：Bheemarao G. Ugarkar、Angelo J. Castellino、Jay M. DaRe、Joseph J. Kopcho、James B. Wiesner、Juergen M. Schanzer、Mark D. Erion

  DOI：10.1021/jm0000259

  日期：2000.7.1

  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.