dibenzyl-(9-methyl-2-phenethyl-9H-purin-6-yl)amine | 496955-55-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并嘧啶类
• 英文名称: dibenzyl-(9-methyl-2-phenethyl-9H-purin-6-yl)amine
• 英文别名: N,N-dibenzyl-9-methyl-2-(2-phenylethyl)purin-6-amine
• CAS: 496955-55-6
• 化学式: C₂₈H₂₇N₅
• 分子量: 433.556
• InChiKey: HHDHHONBJOXPLQ-UHFFFAOYSA-N

物化性质

• 熔点：
  144 °C(Solv: ethanol (64-17-5))
• 沸点：
  578.2±60.0 °C(Predicted)
• 密度：
  1.15±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.7
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  46.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  dibenzyl-(9-methyl-2-phenethyl-9H-purin-6-yl)amine 在 溴 作用下， 以 四氢呋喃 、 甲醇 、 acetate buffer 为溶剂， 反应 12.0h， 以100%的产率得到dibenzyl-(8-bromo-9-methyl-2-phenethyl-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
• 作为产物：
  描述：

  (E)-1-phenyl-(2-tributylstannyl)ethene 在 palladium on activated charcoal 四(三苯基膦)钯 、 氢气 作用下， 以 N-甲基吡咯烷酮 、 乙醇 为溶剂， 20.0~120.0 ℃ 、405.3 kPa 条件下， 反应 2.0h， 生成 dibenzyl-(9-methyl-2-phenethyl-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

• Identification of a 2,4-diaminopyrimidine scaffold targeting Trypanosoma brucei pteridine reductase 1 from the LIBRA compound library screening campaign
  作者：Pasquale Linciano、Gregorio Cullia、Chiara Borsari、Matteo Santucci、Stefania Ferrari、Gesa Witt、Sheraz Gul、Maria Kuzikov、Bernhard Ellinger、Nuno Santarém、Anabela Cordeiro da Silva、Paola Conti、Maria Laura Bolognesi、Marinella Roberti、Federica Prati、Francesca Bartoccini、Michele Retini、Giovanni Piersanti、Andrea Cavalli、Luca Goldoni、Sine Mandrup Bertozzi、Fabio Bertozzi、Enzo Brambilla、Vincenzo Rizzo、Daniele Piomelli、Andrea Pinto、Tiziano Bandiera、Maria Paola Costi

  DOI：10.1016/j.ejmech.2020.112047

  日期：2020.3

  The LIBRA compound library is a collection of 522 non-commercial molecules contributed by various Italian academic laboratories. These compounds have been designed and synthesized during different medicinal chemistry programs and are hosted by the Italian Institute of Technology. We report the screening of the LIBRA compound library against Trypanosoma brucei and Leishmania major pteridine reductase

  LIBRA化合物库是由意大利各个学术实验室提供的522个非商业分子的集合。这些化合物是在不同的药物化学程序中设计和合成的，由意大利技术学院托管。我们报告了针对布鲁氏锥虫和利什曼原虫主要蝶啶还原酶1，TbPTR1和LmPTR1的LIBRA化合物库的筛选。九种化合物具有抗寄生虫PTR1的活性，并被选作基于细胞的寄生虫筛查剂，作为单药和与甲氨蝶呤（MTX）组合使用。鉴定出的最有趣的TbPTR1抑制剂是4-（苄氧基）嘧啶-2,6-二胺（LIB_66）。随后，合成了六种新的LIB_66衍生物以探索其结构-活性-关系（SAR）以及吸收，分布，代谢，排泄和毒性（ADMET）特性。结果表明，PTR1倾向于结合抑制剂，类似于其生物蝶呤/叶酸底物，例如2,4-二氨基嘧啶衍生物。
• [EN] DERIVATIVES OF TRIAZOLYL-IMIDAZOPYRIDINE AND OF THE TRIAZOLYLPURINES USEFUL AS LIGANDS OF THE ADENOSINE A2a RECEPTOR AND THEIR USE AS MEDICAMENTS<br/>[FR] DERIVES DE TRIAZOLYL-IMIDAZOPYRIDINE ET DE TRIAZOLYLPURINES UTILISES EN TANT QUE LIGANDS DU RECEPTEUR DE L'ADENOSINE A2A ET LEUR UTILISATION EN TANT QUE MEDICAMENTS
  申请人：SIGMA TAU IND FARMACEUTI

  公开号：WO2003011864A1

  公开（公告）日：2003-02-13

  Compounds of formula (I) wherein the groups are as defined in the description, said compounds being antagonists of the adenosine A2a receptor and useful as medicaments, in particular for the treatment of Parkinson's disease are disclosed.

  公式为(I)的化合物，其中所述的基团如描述中所定义，这些化合物是腺苷A2a受体拮抗剂，可用作药物，特别用于帕金森病的治疗。
• Derivatives of triazolyl-imidazopyridine and of the triazolylpurines useful as ligandsof the adenosine a2a receptor and their use as medicaments
  申请人：——

  公开号：US20040204428A1

  公开（公告）日：2004-10-14

  1 Compounds of formula (I) wherein the groups are as defined in the description, said compounds being antagonists of the adenosine A 2a receptor and useful as medicaments, in particular for the treatment of Parkinson's disease are disclosed.

  本文揭示了化学式(I)的化合物，其中所述的基团在描述中有定义，这些化合物是腺苷A2A受体的拮抗剂，并且可用作药物，特别是用于治疗帕金森病。
• Derivatives of triazoly-imidazopyridine and of the triazolypurines useful as ligands of the adenosine A2a receptor and their use as medicaments
  申请人：Giorgio Tarzia

  公开号：US20070249638A1

  公开（公告）日：2007-10-25

  Compounds of formula (I) wherein: X is N; R 1 is C 1 -C 6 linear or branched alkyl or C 1 -C 6 linear or branched alkenyl; R 2 is hydrogen, C 1 -C 6 linear or branched alkyl or C 1 -C 6 linear or branched alkenyl, C 6 -C 14 aryl or C 6 -C 14 aryl(C 1 -C 6 ) linear or branched alkyl or C 6 -C 14 aryl(C 1 -C 6 ) 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, C 1 -C 6 alkoxy linear or branched or C 1 -C 6 alkenyloxy linear or branched, amino, optionally mono- or disubstituted with C 1 -C 6 linear or branched alkyl; R 3 is NH 2 , NHR 4 ; R 4 is C 1 -C 6 alkyl or C 1 -C 6 hydroxyalkyl, C 1 -C 3 alkoxyalkyl, amino(C 1 -C 6 )alkyl, where the amino group is optionally substituted with one or two C 1 -C 3 linear or branched alkyl groups, or with one or two C 2 -C 3 alkenyl groups C 6 -C 14 aryl or C 6 -C 14 aryl(C 1 -C 6 )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, C 1 -C 6 alkoxy linear or branched or C 1 -C 6 alkenyloxy linear or branched, amino, mono- or di-substituted with C 1 -C 6 alkyl linear or branched or C 1 -C 6 alkenyl linear or branched; and their pharmaceutically acceptable salts. These compounds are antagonists of the adenosine A 2a receptor and useful as medicaments, in particular for the treatment of Parkinson's disease.

  化合物的式子为(I)，其中：X为N；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，其中芳基可以选择由一个或多个取代基取代，这些取代基可以相同或不同，选自由卤素、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、可选择用C1-C6直链或支链烷基单取代或双取代；R3为NH2、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，其中氨基可以选择用一个或两个C1-C3直链或支链烷基取代或用一个或两个C2-C3烯基取代，或C6-C14芳基或C6-C14芳基(C1-C6)烷基，其中芳基可以选择由一个或多个取代基取代，这些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、可选择用C1-C6直链或支链烷基单取代或双取代或C1-C6直链或支链烯基单取代或双取代；以及它们的药学上可接受的盐。这些化合物是腺苷A2A受体拮抗剂，可用作药物，特别是用于帕金森病的治疗。
• 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.