9-(2-氟苄基)-6-(甲基氨基)-9H-嘌呤 | 101155-02-6

• 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: 9-(2-氟苄基)-6-(甲基氨基)-9H-嘌呤
• 英文名称: BW-A 78U
• 英文别名: 9-(2-Fluorobenzyl)-6-methylamino-9H-purine；9-(2-fluorobenzyl)-6-(methylamino)-9H-purine；9-[(2-fluorophenyl)methyl]-N-methylpurin-6-amine
• CAS: 101155-02-6
• 化学式: C₁₃H₁₂FN₅
• 分子量: 257.27
• InChiKey: MZABAGHILOTTOD-UHFFFAOYSA-N

物化性质

• 溶解度：
  二甲基亚砜：150 mg/ml（583.05 mM）

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  55.6
• 氢给体数：
  1
• 氢受体数：
  5

制备方法与用途

生物活性

BW-A78U 是一种PDE抑制剂，具有抗惊厥活性。

靶点

PDE4
3 μM (IC50)

体外研究

BW-A78U 是一个PDE4抑制剂，其半数抑制浓度（IC50）为3 μM。BW-A78U 未能显著抑制花生四烯酸的释放，并且对脂多糖（LPS）诱导的TNF-α释放无效。

反应信息

• 作为产物：
  描述：

  9-(2-Fluorobenzyl)-6-formamido-9H-purine 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 以20%的产率得到9-(2-氟苄基)-6-(甲基氨基)-9H-嘌呤
  参考文献：
  名称：

  9-（2-氟苄基）-6-甲基氨基-9 H-嘌呤的合成

  摘要：

  据报道由九种不同的前体合成9-（2-氟苄基）-6-甲基氨基-9 H-嘌呤（1）。化合物1的制备是通过将6-氯-9-（2-氟苄基）-9-甲氨基化ħ嘌呤（4）中，由6- methylaminepurine（烷基化5）或形式9-（2-氟苄基）-1- methyladeninium碘化（8）通过Dimroth重排。6-氨基嘌呤的选择性两步骤甲基化6用氢化物还原的6- formamidopurine完成9，6-dimethylaminomethyleneaminopurine 10或6-苯硫基嘌呤11，得到1化合物1也通过dethiation或2-甲硫基嘌呤的还原脱氯制备16或8氯嘌呤19，分别，或由6-水解Ñ -methylformamidopurine 12，将其从6-二甲基氨基制备13通过选择性氧化。

  DOI：

  10.1002/jhet.5570230445

文献信息

• [EN] NOVEL TRIARYL DERIVATIVES USEFUL AS MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS<br/>[FR] NOUVEAUX DÉRIVÉS DE TRIARYLE UTILES EN TANT QUE MODULATEURS DE RÉCEPTEURS D'ACÉTYLCHOLINE NICOTINIQUES
  申请人：NEUROSEARCH AS

  公开号：WO2009112461A1

  公开（公告）日：2009-09-17

  This invention relates to novel triaryl derivatives derivatives, formula (I), a stereoisomer thereof or a mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof, wherein all of X, Y and Z represent CH; or one or two of X, Y and Z represent N; and the others of X, Y and Z represent CH; and R1, R2, R3, R4 and R5. independently of each other, represent hydrogen, halo, trifluoromethyl, trifluoromethoxy, cyano, hydroxyl, alkoxy, alkyl, amino or sulfamoyl; or R1 and R2, together with the phenyl ring to which they are attached form an indolyl ring or a benzo-dioxolyl ring; and R3, R4 and R5 are as defined above; and R6 represents amino or nitro, which are found to be modulators of the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

  该发明涉及新型三芳基衍生物，公式（I），其立体异构体或其立体异构体的混合物，或其药学上可接受的盐，其中X、Y和Z均表示CH；或X、Y和Z中的一个或两个表示N；其余的X、Y和Z表示CH；以及R1、R2、R3、R4和R5。独立地，它们表示氢、卤素、三氟甲基、三氟甲氧基、氰基、羟基、烷氧基、烷基、氨基或磺胺基；或者R1和R2，与它们连接的苯环一起形成吲哚基环或苯并二氧杂吲哚基环；而R3、R4和R5如上所定义；以及R6表示氨基或硝基，这些被发现是尼古丁乙酰胆碱受体的调节剂。由于其药理学特性，本发明的化合物可能对治疗与中枢神经系统（CNS）的胆碱系统、外周神经系统（PNS）、平滑肌收缩、内分泌疾病、神经退行性疾病、炎症、疼痛以及由于滥用化学物质终止而引起的戒断症状等多种疾病或疾病具有用处。
• NOVEL TRIARYL DERIVATIVES USEFUL AS MODULATORS OF NICOTINIC ACETYLCHOLINE RECEPTORS
  申请人：Nardi Antonio

  公开号：US20110105543A1

  公开（公告）日：2011-05-05

  This invention relates to novel triaryl derivatives, formula (I), a stereoisomer thereof or a mixture of its stereoisomers, or a pharmaceutically acceptable salt thereof, wherein all of X, Y and Z represent CH; or one or two of X, Y and Z represent N; and the others of X, Y and Z represent CH; and R 1 , R 2 , R 3 , R 4 and R 5 . independently of each other, represent hydrogen, halo, tri-fluoromethyl, trifluoromethoxy, cyano, hydroxyl, alkoxy, alkyl, amino or sulfamoyl; or R 1 and R 2 , together with the phenyl ring to which they are attached form an indolyl ring or a benzo-dioxolyl ring; and R 3 , R 4 and R 5 are as defined above; and R 6 represents amino or nitro, which are found to be modulators of the nicotinic acetylcholine receptors. Due to their pharmacological profile the compounds of the invention may be useful for the treatment of diseases or disorders as diverse as those related to the cholinergic system of the central nervous system (CNS), the peripheral nervous system (PNS), diseases or disorders related to smooth muscle contraction, endocrine diseases or disorders, diseases or disorders related to neuro-degeneration, diseases or disorders related to inflammation, pain, and withdrawal symptoms caused by the termination of abuse of chemical substances.

  本发明涉及新型三芳基衍生物，式（I），其立体异构体或其立体异构体混合物，或其药学上可接受的盐，其中X、Y和Z均代表CH; 或X、Y和Z中的一个或两个代表N; 而X、Y和Z的其他代表CH; R1、R2、R3、R4和R5独立地表示氢、卤、三氟甲基、三氟甲氧基、氰基、羟基、烷氧基、烷基、氨基或磺酰氨基; 或R1和R2与它们附着的苯环一起形成吲哚基环或苯并二噁英基环; 而R3、R4和R5如上定义; 而R6表示氨基或硝基，发现它们是烟碱乙酰胆碱受体的调节剂。由于它们的药理特性，本发明的化合物可能对治疗与中枢神经系统（CNS）和外周神经系统（PNS）的胆碱能系统相关的疾病或疾病，与平滑肌收缩有关的疾病或疾病，内分泌疾病或疾病，神经退行性疾病或疾病，与炎症有关的疾病或疾病，疼痛以及由化学物质滥用终止引起的戒断症状可能有用。
• Heterocyclic compounds
  申请人：THE WELLCOME FOUNDATION LIMITED

  公开号：EP0157637A2

  公开（公告）日：1985-10-09

  The present invention provides a group of novel compounds useful in the treatment of CNS disorders such as epilepsy, the compounds having the general formula (III): wherein R5 is hydrogen, methyl or ethyl; R6 is hydrogen, methyl, hydroxymethyl, methoxymethyl, ethyl, n-propyl, isopropyl, cyclopropyl, cyclopentyl, or cyclopropylmethyl and R7 is hydrogen or fluorine attached to the 6- or 5- position of the phenyl ring. Also provided are methods for the preparation of compounds of the formula (III) and pharmaceutical compositions containing the said compounds.

  本发明提供了一组可用于治疗癫痫等中枢神经系统疾病的新型化合物，这些化合物具有通式(III)： 其中R5是氢、甲基或乙基；R6是氢、甲基、羟甲基、甲氧基甲基、乙基、正丙基、异丙基、环丙基、环戊基或环丙基甲基；R7是氢或连接到苯环6-位或5-位的氟。 还提供了制备式（III）化合物和含有上述化合物的药物组合物的方法。
• 9-Benzyladenines:  Potent and Selective cAMP Phosphodiesterase Inhibitors
  作者：Jean-Jacques Bourguignon、Laurent Désaubry、Pierre Raboisson、Camille-Georges Wermuth、Claire Lugnier

  DOI：10.1021/jm960827x

  日期：1997.6.1
• 9-(2-Fluorobenzyl)-6-(methylamino)-9H-purine hydrochloride. Synthesis and anticonvulsant activity
  作者：James L. Kelley、Francis E. Soroko

  DOI：10.1021/jm00157a003

  日期：1986.7