3-benzyl-5-phenyl-7-chloro-3H-1,2,3-triazolo[4,5-d]pyrimidine | 433922-12-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: 3-benzyl-5-phenyl-7-chloro-3H-1,2,3-triazolo[4,5-d]pyrimidine
• 英文别名: 6-chloro-2-phenyl-9-benzyl-8-azaadenine；6-chloro-2-phenyl-9-benzyl-8-azapurine；6-chloro-9-benzyl-2-phenyl-8-azapurine；3-benzyl-7-chloro-5-phenyl-1,2,3-triazolo[4,5-d]pyrimidine；3H-1,2,3-Triazolo[4,5-d]pyrimidine, 7-chloro-5-phenyl-3-(phenylmethyl)-；3-benzyl-7-chloro-5-phenyltriazolo[4,5-d]pyrimidine
• CAS: 433922-12-4
• 化学式: C₁₇H₁₂ClN₅
• 分子量: 321.769
• InChiKey: VNSBTHYARQCCRU-UHFFFAOYSA-N

物化性质

• 熔点：
  176-179 °C(Solv: benzene (71-43-2))
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  23
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  56.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-benzyl-5-phenyl-7-chloro-3H-1,2,3-triazolo[4,5-d]pyrimidine 在 氨 作用下， 以 乙醇 、 乙腈 为溶剂， 反应 11.0h， 生成
  参考文献：
  名称：

  2,9-Disubstituted-N6-(arylcarbamoyl)-8-azaadenines as new selective A3 adenosine receptor antagonists: Synthesis, biochemical and molecular modelling studies

  摘要：

  A number of N-6-(N-arylcarbamoyl)-2-substituted-9-benzyl-8-azaadenines, obtained by a modification of the synthetic scheme used to prepare selective A(1) ligands, by only three or two steps, are described. At first we prepared a series of 2-phenyl-9-benzyl-8-azaadenines having as N-6 substituent a variously substituted N-phenylcarbamoyl group. Some of these derivatives demonstrated good affinity towards the A(3) subtype but low selectivity. Compounds having p-CF3, p-F and p-OCH3, as substituents on the phenylcarbamoyl group were selected as lead compounds for the second part of this study. Without modifying the N-6 substituent, which would assure A(3) affinity, we varied the 9 and 2 positions on these molecules to enhance selectivity. Some compounds having a p-methyl group on the 2-phenyl substituent showed a very good affinity and selectivity for the A(3) subtype, revealing the first class of A(3) adenosine receptor selective antagonists with a bicyclic structure strictly correlated to the adenine nucleus. The molecular modelling work, carried out using the DOCK program, supplied two models which may be useful for a better understanding of the binding modes. Both models highlighted the preferred interacting tautomeric forms of the antagonists for human A(1) and A(3) receptors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.063
• 作为产物：
  描述：

  5-氨基-1-苄基-1H-1,2,3-噻唑-4-羧胺 在 N,N-二乙基苯胺 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 14.0h， 生成 3-benzyl-5-phenyl-7-chloro-3H-1,2,3-triazolo[4,5-d]pyrimidine
  参考文献：
  名称：

  2,9-Disubstituted-N6-(arylcarbamoyl)-8-azaadenines as new selective A3 adenosine receptor antagonists: Synthesis, biochemical and molecular modelling studies

  摘要：

  A number of N-6-(N-arylcarbamoyl)-2-substituted-9-benzyl-8-azaadenines, obtained by a modification of the synthetic scheme used to prepare selective A(1) ligands, by only three or two steps, are described. At first we prepared a series of 2-phenyl-9-benzyl-8-azaadenines having as N-6 substituent a variously substituted N-phenylcarbamoyl group. Some of these derivatives demonstrated good affinity towards the A(3) subtype but low selectivity. Compounds having p-CF3, p-F and p-OCH3, as substituents on the phenylcarbamoyl group were selected as lead compounds for the second part of this study. Without modifying the N-6 substituent, which would assure A(3) affinity, we varied the 9 and 2 positions on these molecules to enhance selectivity. Some compounds having a p-methyl group on the 2-phenyl substituent showed a very good affinity and selectivity for the A(3) subtype, revealing the first class of A(3) adenosine receptor selective antagonists with a bicyclic structure strictly correlated to the adenine nucleus. The molecular modelling work, carried out using the DOCK program, supplied two models which may be useful for a better understanding of the binding modes. Both models highlighted the preferred interacting tautomeric forms of the antagonists for human A(1) and A(3) receptors. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.04.063

文献信息

• New N6- or N(9)-hydroxyalkyl substituted 8-azaadenines or adenines as effective A1 adenosine receptor ligands
  作者：Giuliana Biagi、Irene Giorgi、Michele Leonardi、Oreste Livi、Federica Pacchini、Valerio Scartoni、Barbara Costa、Antonio Lucacchini

  DOI：10.1016/s0223-5234(03)00147-8

  日期：2003.9

  In this paper we describe synthesis and biological assays of some A(1) ligands more water-soluble than the effective, but very lipophilic, 8-azaadenines and adenines discovered in the past and obtained introducing on N(6) or N(9) substituent a hydroxy group. Five of the new N(6)-hydroxyalkyl- and N(6)-hydroxycycloalkyl-2-phenyl-9-benzyl-8-azaadenines showed very high affinity (Ki<40 nM) and selectivity

  在本文中，我们描述了一些A（1）配体的合成和生物学分析，这些配体比过去发现并在N（6）或N（9）上引入的有效但非常亲脂的8-azaadenines和腺嘌呤水溶性更高。取代基是羟基。新的N（6）-羟烷基-和N（6）-羟基环烷基-2-苯基-9-苄基-8-氮杂腺嘌呤中的五个显示出非常高的亲和力（Ki <40 nM）和对A（1）腺苷受体的选择性。在制备的2-苯基-9-（2-羟基-3-烷基）-8-氮杂腺嘌呤或腺嘌呤中，具有较高A（1）亲和力和选择性的化合物可生成2-苯基-9-（2-羟基-3 -丙基）-N（6）-环戊基-和环己基-8-氮杂腺嘌呤，Ki分别为2.2 +/- 0.2 nM和2.8 +/- 0.3 nM。从水溶性的观点来看，最有趣的化合物是2-苯基-9-（2-羟基-3-丙基）-8-氮杂腺嘌呤，CLogP为1。
• Compounds containing a N-heteroaryl moiety linked to fused ring moieties for the inhibition of NAD(P)H oxidases and platelet activation
  申请人：Vasopharm Biotech GmbH

  公开号：EP1598354A1

  公开（公告）日：2005-11-23

  The invention relates to compounds containing a N-heteroaryl moiety, which is linked via oxygen, sulfur or nitrogen, or via a methylene bridge and oxygen, sulfur or nitrogen to a fused ring moiety, in particular to the 1,2,3-triazolo[4,5-d]pyrimidine-7-yl radical. The invention also relates to a process for the preparation of said compounds and the use thereof in drugs for the treatment of NAD(P)H oxidases-related diseases and disorders and inhibition of platelet activation.

  该发明涉及含有N-杂环芳基团的化合物，该化合物通过氧、硫或氮，或通过亚甲基桥和氧、硫或氮连接到融合环基团，特别是到1,2,3-三唑并[4,5-d]嘧啶-7-基自由基。该发明还涉及一种制备所述化合物的方法以及在治疗NAD(P)H氧化酶相关疾病和疾病以及抑制血小板活化的药物中的使用。
• N6-Cycloalkyl-2-phenyl-3-deaza-8-azaadenines: a new class of A1 adenosine receptor ligands. A comparison with the corresponding adenines and 8-azaadenines
  作者：Giuliana Biagi、Irene Giorgi、Oreste Livi、Antonio Nardi、Federica Pacchini、Valerio Scartoni、Antonio Lucacchini

  DOI：10.1016/j.ejmech.2003.09.003

  日期：2003.11

  -1,2,3-triazolo[4,5-c]pyridines were prepared and assayed as A1 adenosine receptor ligands. The 1H-1,2,3-triazolo[4,5-c]pyridines were obtained starting from N,N-diethyl-1-benzyl-4-carboxyamido-5-methyl-1H-1,2,3-triazole by lithiation in anhydrous tetrahydrofurane in the presence of benzonitrile. The usual work up afforded the isolation of 1-benzyl-6-phenyl-1H-1,2,3-triazolo[4,5-c]pyridin-4-one which

  几种9-苄基-N6-环烷基-2-苯基ade啶，9-苄基-N6-环烷基-2-苯基-8-氮杂腺嘌呤和4-环烷基氨基-1-苄基-6-苯基-1H-1,2,3-三唑制备[4，5-c]吡啶并测定为A1腺苷受体配体。1H-1,2,3-三唑并[4,5-c]吡啶是从N，N-二乙基-1-苄基-4-羧基酰胺基-5-甲基-1H-1,2,3-三唑开始得到的苯甲腈存在下，在无水四氢呋喃中进行锂化反应。通常的处理提供了分离的1-苄基-6-苯基-1H-1,2,3-三唑并[4,5-c]吡啶-4-酮，其用三氯氧磷和环烷基胺处理。一些化合物表现出高亲和力和选择性，Ki值的趋势对应于9-苄基-N6-环烷基-2-苯基ade啶和9-苄基-N6-环烷基-2-苯基-8-氮杂腺嘌呤的系列，因此它们可以是被认为是生物等排体。
• Characterization and preliminary use of 1-, 2- and 3-methyl-5-phenyl-7-chloro-1,2,3-triazolo[4,5-d]pyrimidine as reaction intermediates
  作者：Giuliana Biagi、Irene Giorgi、Oreste Livi、Valerio Scartoni、Pier Luigi Barili

  DOI：10.1016/s0014-827x(03)00095-8

  日期：2003.8

  spectroscopic methods, of three new N-methyl-5-phenyl-7-chloro-1,2,3-triazolo[4,5-d]pyrimidine isomers 3a, 3b and 3c. For comparison purpose the 3-benzyl-5-phenyl-7-chloro-1,2,3-triazolo[4,5-d]pyrimidine (7) was also prepared. Starting from the isomer mixture 3a-c and the chloroderivative 7, by nucleophilic substitution reaction with ethyl carbazate and subsequent intramolecular cyclization, the new

  本文报道了三种新的N-甲基-5-苯基-7-氯-1,2,3-三唑并[4,5-d]嘧啶异构体3a，3b和3c的合成和表征。为了比较，还制备了3-苄基-5-苯基-7-氯-1,2,3-三唑并[4,5-d]嘧啶（7）。从异构体混合物3a-c和氯代衍生物7开始，通过与氨基甲酸乙酯的亲核取代反应以及随后的分子内环化反应，制备了新的三环衍生物5a-c和9，并针对苯二氮卓和腺苷A1和A2A受体进行了测试。
• [EN] COMPOUNDS CONTAINING A N-HETEROARYL MOIETY LINKED TO FUSED RING MOIETIES FOR THE INHIBITION OF NAD(P)H OXIDASES AND PLATELET ACTIVATION<br/>[FR] COMPOSES COMPRENANT UNE FRACTION N-HETEROARYLE LIEE A DES FRACTIONS DE NOYAU FUSIONNEES ET DESTINES A L'INHIBITION DES NAD(P)H OXYDASES ET DE L'ACTIVATION DE PLAQUETTES
  申请人：VASOPHARM BIOTECH GMBH

  公开号：WO2005111041A1

  公开（公告）日：2005-11-24

  The invention relates to compounds containing a N-heteroaryl moiety, which is linked via oxygen, sulfur or nitrogen, or via a methylene bridge and oxygen, sul­fur or nitrogen to a fused ring moiety, in particular to the 1,2,3-triazolo[4,5­d]pyrimidine-7-yl radical. The invention also relates to a process for the prepara­tion of said compounds and the use thereof in drugs for the treatment of NAD(P)H oxidases-related diseases and disorders and inhibition of platelet activation.

  本发明涉及一种含有N-杂芳基基团的化合物，该基团通过氧、硫或氮或通过亚甲基桥和氧、硫或氮连接到融合环基团上，特别是1,2,3-三唑并[4,5-d]嘧啶-7-基自由基。本发明还涉及制备该化合物的方法以及在治疗NAD（P）H氧化酶相关疾病和障碍以及抑制血小板活化的药物中使用该化合物的用途。