dibenzyl(2-n-butyl-9-methyl-9H-purin-6-yl)amine | 496955-50-1

• 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: dibenzyl(2-n-butyl-9-methyl-9H-purin-6-yl)amine
• 英文别名: N,N-dibenzyl-2-butyl-9-methyl-9H-purin-6-amine；N,N-dibenzyl-2-butyl-9-methylpurin-6-amine
• CAS: 496955-50-1
• 化学式: C₂₄H₂₇N₅
• 分子量: 385.512
• InChiKey: PNNFBLVUNIKSBC-UHFFFAOYSA-N

物化性质

• 熔点：
  72-73 °C
• 沸点：
  511.4±60.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  29
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  46.8
• 氢给体数：
  0
• 氢受体数：
  4

安全信息

• 储存条件：
  2-8°C

反应信息

• 作为反应物：
  描述：

  dibenzyl(2-n-butyl-9-methyl-9H-purin-6-yl)amine 以100的产率得到dibenzyl-(8-bromo-2-n-butyl-9-methyl-9H-purin-6-yl)amine
  参考文献：
  名称：

  Derivatives of triazoly-imidazopyridine useful as ligands of the adenosine A2a receptor and their use as medicaments

  摘要：

  化合物的化学式为（I），其中：X为CH或CH—R2；R1为C1-C6直链或支链烷基或C1-C6直链或支链烯基；R2为氢，C1-C6直链或支链烷基或C1-C6直链或支链烯基，C6-C14芳基或C6-C14芳基（C1-C6）直链或支链烷基或C6-C14芳基（C1-C6）直链或支链烯基，芳基基团可以选用一个或多个取代基，取代基可以相同或不同，选自卤素，羟基，C1-C6直链或支链烷氧基或C1-C6直链或支链烯氧基，氨基，可选用C1-C6直链或支链烷基单取代或双取代的氨基；R3为NH2或NHR4；R4为C1-C6烷基或C1-C6羟基烷基，C1-C3烷氧基烷基，氨基（C1-C6）烷基，其中氨基可以选择一个或两个C1-C3直链或支链烷基取代或一个或两个C2-C3烯基取代，或C6-C14芳基或C6-C14芳基（C1-C6）烷基，芳基基团可以选用一个或多个取代基，取代基可以相同或不同，选自卤素，羟基，C1-C6直链或支链烷氧基或C1-C6直链或支链烯氧基，氨基，可选用C1-C6直链或支链烷基单取代或双取代的氨基或C1-C6直链或支链烯基单取代或双取代的氨基；以及其药学上可接受的盐。这些化合物是腺苷A2a受体拮抗剂，特别适用于帕金森病的治疗。

  公开号：

  US07528252B2
• 作为产物：
  描述：

  N,N-dibenzyl-2-chloro-9H-purin-6-amine 在 四(三苯基膦)钯 、 potassium carbonate 作用下， 以 N-甲基吡咯烷酮 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 dibenzyl(2-n-butyl-9-methyl-9H-purin-6-yl)amine
  参考文献：
  名称：

  2-n-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine and Analogues as A_2A Adenosine Receptor Antagonists. Design, Synthesis, and Pharmacological Characterization

  摘要：

  Two types of adenosine receptor ligands were designed, i.e., 9H-purine and 1H-imidazo[4,5-c]pyridines, to obtain selective A(2A) antagonists, and we report here their synthesis and binding affinities for the four adenosine receptor subtypes A(1), A(2A), A(2B) and A(3). The design was carried out on the basis of the molecular modeling of a number of potent adenosine receptor antagonists described in the literature. Three compounds (25b-d) showed an interesting affinity and selectivity for the A(2A) subtype. One of them, i.e., ST1535 (2-n-butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine, 25b) (K-i A(2A) = 6.6 nM, K-i A(1)/A(2A) = 12; K-i A(2B)/A(2A) = 58; K-i A(3)/A(2A) > 160), was selected for in vivo study and shown to induce a dose-related increase in locomotor activity, suggestive of an A(2A) antagonist type of activity.

  DOI：

  10.1021/jm058018d

文献信息

• Direct B-Alkyl Suzuki−Miyaura Cross-Coupling of 2-Halopurines. Practical Synthesis of ST1535, a Potent Adenosine A_2A Receptor Antagonist
  作者：Francesca Bartoccini、Walter Cabri、Diana Celona、Patrizia Minetti、Giovanni Piersanti、Giorgio Tarzia

  DOI：10.1021/jo101027h

  日期：2010.8.6

  The scope and limitations of using palladium-catalyzed cross-coupling reactions of diverse butyl metal species with two different 2-halopurines were evaluated. While tributylboranes reacted readily and regioselectively with both 2-chloro-6-dibenzylaminopurines and 2-iodo-6-chloropurines, all the other alkyl metal species were much less reactive and gave very poor yield and/or selectivity of the desired product. This protocol was applied to the synthesis of an important adenosine A(2A) receptor antagonist, ST1535.
• Development of a practical and sustainable strategy for the synthesis of ST1535 by an iron-catalyzed Kumada cross-coupling reaction
  作者：Francesca Bartoccini、Giovanni Piersanti、Silvia Armaroli、Alberto Cerri、Walter Cabri

  DOI：10.1016/j.tetlet.2014.01.030

  日期：2014.2

  A simple, convenient, and environmentally friendly route to ST1535 employing an iron-catalyzed cross-coupling reaction and butylmagnesium chloride is described. (C) 2014 Elsevier Ltd. All rights reserved.
• 2-<i>n</i>-Butyl-9-methyl-8-[1,2,3]triazol-2-yl-9<i>H</i>-purin-6-ylamine and Analogues as A_2A Adenosine Receptor Antagonists. Design, Synthesis, and Pharmacological Characterization
  作者：Patrizia Minetti、Maria Ornella Tinti、Paolo Carminati、Massimo Castorina、Maria Assunta Di Cesare、Stefano Di Serio、Grazia Gallo、Orlando Ghirardi、Fabrizio Giorgi、Luca Giorgi、Giovanni Piersanti、Francesca Bartoccini、Giorgio Tarzia

  DOI：10.1021/jm058018d

  日期：2005.11.1

  Two types of adenosine receptor ligands were designed, i.e., 9H-purine and 1H-imidazo[4,5-c]pyridines, to obtain selective A(2A) antagonists, and we report here their synthesis and binding affinities for the four adenosine receptor subtypes A(1), A(2A), A(2B) and A(3). The design was carried out on the basis of the molecular modeling of a number of potent adenosine receptor antagonists described in the literature. Three compounds (25b-d) showed an interesting affinity and selectivity for the A(2A) subtype. One of them, i.e., ST1535 (2-n-butyl-9-methyl-8-[1,2,3]triazol-2-yl-9H-purin-6-ylamine, 25b) (K-i A(2A) = 6.6 nM, K-i A(1)/A(2A) = 12; K-i A(2B)/A(2A) = 58; K-i A(3)/A(2A) > 160), was selected for in vivo study and shown to induce a dose-related increase in locomotor activity, suggestive of an A(2A) antagonist type of activity.
• Derivatives of triazoly-imidazopyridine useful as ligands of the adenosine A2a receptor and their use as medicaments
  申请人：Sigma-Tau Industrie Farmaceutiche Riunite S.p.A.

  公开号：US07528252B2

  公开（公告）日：2009-05-05

  Compounds of formula (I) wherein: X is CH or CH—R2; R1 is C1-C6 linear or branched alkyl or C1-C6 linear or branched alkenyl; R2 is hydrogen, C1-C6 linear or branched alkyl or C1-C6 linear or branched alkenyl, C6-C14 aryl or C6-C14 aryl(C1-C6) linear or branched alkyl or C6-C14 aryl(C1-C6) linear or branched alkenyl, with the aryl group optionally substituted by one or more substituents, either the same or different, selected from the group consisting of halogen, hydroxy, C1-C6 alkoxy linear or branched or C1-C6 alkenyloxy linear or branched, amino, optionally mono- or disubstituted with C1-C6 linear or branched alkyl; R3 is NH2, or NHR4; R4 is C1-C6 alkyl or C1-C6 hydroxyalkyl, C1-C3 alkoxyalkyl, amino(C1-C6)alkyl, where the amino group is optionally substituted with one or two C1-C3 linear or branched alkyl groups, or with one or two C2-C3 alkenyl groups C6-C14 aryl or C6-C14 aryl(C1-C6)alkyl, with the aryl group optionally substituted by one or more substituents, either the same or different, selected from the group consisting by halogen, hydroxy, C1-C6 alkoxy linear or branched or C1-C6 alkenyloxy linear or branched, amino, mono- or di-substituted with C1-C6 alkyl linear or branched or C1-C6 alkenyl linear or branched; and their pharmaceutically acceptable salts. These compounds are antagonists of the adenosine A2a receptor and useful as medicaments, in particular for the treatment of Parkinson's disease.

  化合物的化学式为（I），其中：X为CH或CH—R2；R1为C1-C6直链或支链烷基或C1-C6直链或支链烯基；R2为氢，C1-C6直链或支链烷基或C1-C6直链或支链烯基，C6-C14芳基或C6-C14芳基（C1-C6）直链或支链烷基或C6-C14芳基（C1-C6）直链或支链烯基，芳基基团可以选用一个或多个取代基，取代基可以相同或不同，选自卤素，羟基，C1-C6直链或支链烷氧基或C1-C6直链或支链烯氧基，氨基，可选用C1-C6直链或支链烷基单取代或双取代的氨基；R3为NH2或NHR4；R4为C1-C6烷基或C1-C6羟基烷基，C1-C3烷氧基烷基，氨基（C1-C6）烷基，其中氨基可以选择一个或两个C1-C3直链或支链烷基取代或一个或两个C2-C3烯基取代，或C6-C14芳基或C6-C14芳基（C1-C6）烷基，芳基基团可以选用一个或多个取代基，取代基可以相同或不同，选自卤素，羟基，C1-C6直链或支链烷氧基或C1-C6直链或支链烯氧基，氨基，可选用C1-C6直链或支链烷基单取代或双取代的氨基或C1-C6直链或支链烯基单取代或双取代的氨基；以及其药学上可接受的盐。这些化合物是腺苷A2a受体拮抗剂，特别适用于帕金森病的治疗。