N-(6-氨基-2,4-二氧代-3-丙基-1,2,3,4-四氢-5-嘧啶基)环戊烷甲酰胺 | 152529-70-9

• 分子结构分类: 有机化合物 - 有机氮化合物
• 中文名称: N-(6-氨基-2,4-二氧代-3-丙基-1,2,3,4-四氢-5-嘧啶基)环戊烷甲酰胺
• 英文名称: 6-amino-5-cyclopentanecarboxamido-2,4-dioxo-3-propyl-1,2,3,4-tetrahydropyrimidine
• 英文别名: 6-amino-5-cyclopentylcarboxamido-3-propyluracil；Cyclopentane carboxylic acid (6-amino-2,4-dioxo-3-propyl-1,2,3,4-tetra hydro-pyrimidin-5-yl)-amide；N-(6-amino-2, 4-dioxo-3-propyl-1H-pyrimidin-5-yl)cyclopentanecarboxamide；N-(6-Amino-2,4-dioxo-3-propyl-1,2,3,4-tetrahydropyrimidin-5-yl)cyclopentanecarboxamide；N-(6-amino-2,4-dioxo-3-propyl-1H-pyrimidin-5-yl)cyclopentanecarboxamide
• CAS: 152529-70-9
• 化学式: C₁₃H₂₀N₄O₃
• 分子量: 280.327
• InChiKey: YHUKSBZTJSINBW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  N-(6-氨基-2,4-二氧代-3-丙基-1,2,3,4-四氢-5-嘧啶基)环戊烷甲酰胺 在 N-甲基吡咯烷酮 、 五氯化磷 、 三氯氧磷 作用下， 反应 12.0h， 生成 8-Cyclopentyl-2-phenylamino-1-propyl-1,7-dihydro-purin-6-one
  参考文献：
  名称：

  新型，有效和选择性的次黄嘌呤类似物作为腺苷A1受体拮抗剂的设计与合成及其生物学评价。

  摘要：

  多管齐下的方法用于从常见的中间体III合成各种C-8环戊基次黄嘌呤类似物的文库。鉴定了几种有效的和选择性的化合物，并评估了Wistar大鼠的药代动力学（PK）特性。选择具有可接受的PK参数的化合物14之一用于体内原发性急性利尿模型的测试。该化合物在该模型中显示出明显的利尿活性。

  DOI：

  10.1016/j.bmc.2017.02.029
• 作为产物：
  描述：

  环戊酸 、 5,6-二氨基-3-丙基嘧啶-2,4(1h,3h)-二酮 在 1-dimethylaminopropyl-3-ethylcarbodiimide hydrochloride 作用下， 以 甲醇 为溶剂， 以93%的产率得到N-(6-氨基-2,4-二氧代-3-丙基-1,2,3,4-四氢-5-嘧啶基)环戊烷甲酰胺
  参考文献：
  名称：

  对位黄嘌呤类似物（1,7-二取代的黄嘌呤）和其他在3位未取代的黄嘌呤的合成：腺苷受体的结构活性关系。

  摘要：

  开发了用于制备各种3-未取代的黄嘌呤的合成方法，包括对黄嘌呤类似物（1,7-二取代的黄嘌呤）和1,8-二取代的黄嘌呤。1-取代的黄嘌呤的甲硅烷基化，然后在7-位的烷基化提供了一种简便的途径生产对黄嘌呤类似物。三（三甲基甲硅烷基）-6-氨基尿嘧啶的区域选择性烷基化提供了3-取代的6-氨基尿嘧啶，其通过标准方法转化为1,8-二取代的黄嘌呤。3-取代的5-环戊烷羧酰胺基和5-（苯甲酰基氨基）-6-氨基尿嘧啶的闭环需要剧烈的反应条件。在这些和其他具有1、3、7、8和9位取代基的黄嘌呤的结合测定中，确定了对大脑A1和A2腺苷受体的亲和力。为了在腺苷受体上具有高亲和力，必须在1位进行取代。1，3-二取代的黄嘌呤通常比1，7-二取代的黄嘌呤具有更高的亲和力。1,8-二取代的黄嘌呤对腺苷受体具有高亲和力。一些对A1受体具有高度选择性。

  DOI：

  10.1021/jm00074a015

文献信息

• SUBSTITUTED FUSED PYRIMIDINE COMPOUNDS, ITS PREPARATION AND USES THEREOF
  申请人：Ramdas Vidya

  公开号：US20120225812A1

  公开（公告）日：2012-09-06

  The present invention provides substituted fused pyrimidine compounds of formula (I), their tautomers, polymorphs, stereoisomers, prodrugs, solvates, pharmaceutically acceptable salts, pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by adenosine receptor (AR) activity. The present invention also provides process of preparation of compounds of formula (I).

  本发明提供了公式（I）的取代融合嘧啶化合物，它们的互变异构体、多型体、立体异构体、前药、溶剂合物、药用可接受盐、含有它们的药物组合物以及治疗通过腺苷受体（AR）活性介导的病症和疾病的方法。本发明还提供了制备公式（I）化合物的方法。
• [EN] SUBSTITUTED FUSED PYRIMIDINE COMPOUNDS, ITS PREPARATION AND USES THEREOF<br/>[FR] COMPOSÉS PYRIMIDINE FUSIONNÉS SUBSTITUÉS, LEUR PRÉPARATION ET LEURS UTILISATIONS
  申请人：ADVINUS THERAPEUTICS PRIVATE LTD

  公开号：WO2011055391A1

  公开（公告）日：2011-05-12

  The present invention provides substituted fused pyrimidine compounds of formula (I), their tautomers, polymorphs, stereoisomers, prodrugs, solvates, pharmaceutically acceptable salts, pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by adenosine receptor (AR) activity. The present invention also provides process of preparation of formula (I).

  本发明提供了式(I)的取代融合嘧啶化合物，其互变异构体、多型体、立体异构体、前药、溶剂合物、药用可接受盐、含有它们的药物组合物以及治疗由腺苷受体（AR）活性介导的疾病和症状的方法。本发明还提供了制备式(I)的方法。
• Substituted fused pyrimidine compounds, its preparation and uses thereof
  申请人：Ramdas Vidya

  公开号：US08796290B2

  公开（公告）日：2014-08-05

  The present invention provides substituted fused pyrimidine compounds of formula (I), their tautomers, polymorphs, stereoisomers, prodrugs, solvates, pharmaceutically acceptable salts, pharmaceutical compositions containing them and methods of treating conditions and diseases that are mediated by adenosine receptor (AR) activity. The present invention also provides processes for preparation of compounds of formula (I).

  本发明提供了式（I）的取代融合嘧啶化合物，它们的互变异构体、多晶形态、立体异构体、前药、溶剂化物、药学上可接受的盐、含有它们的制药组合物以及治疗通过腺苷受体（AR）活性介导的条件和疾病的方法。本发明还提供了制备式（I）化合物的方法。
• Development of Spin-Labeled Probes for Adenosine Receptors
  作者：Janez Ilaš、Slavko Pečar、Jörg Hockemeyer、Harald Euler、Armin Kirfel、Christa E. Müller

  DOI：10.1021/jm049513x

  日期：2005.3.1

  Functionalized xanthine derivatives bearing a nitroxide moiety at the 3- or 8-position were synthesized as electron paramagnetic resonance (EPR) probes. The 8-cyclopentyl-1-propylxanthine derivative 4, spin-labeled at N3 by substitution with a nitroxide-bearing dihydropyrrole moiety, was a potent and selective A(1) adenosine receptor antagonist (K-i for A(1) 5.5 nM, 1600-fold selectivity vs A(2A), > 200-fold vs A(2B), and 310-fold vs A(3) adenosine receptors). 8-(1-Oxyl-2,2,5,5-tetramethyl-2,5-dihydro-1H-pyrrol-3-yl)-1,3-dipropylxanthine 10 (K-i for A(1) 8.2 nM) was similarly potent and selective, while 8-(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)-1,3-dipropylxanthine 11 (K-i for A(1) 160 nM) exhibited significantly lower affinity for A(1) adenosine receptors. 8-[4-(((1-Oxyl-2,2,6,6-tetramethylpiperidin-4-yl)amino)-2-oxoethoxy)phenyl]-1-propylxanthine 14, a 3-unsubstituted xanthine derivative, was found to be a potent A(2B) adenosine receptor antagonist (K-i for A(2B) 48 nM) but also exhibited high affinity for A(1) receptors (K-i for A(1) 15.7 nM). An X-ray structure of compound 10 was obtained, confirming the proposed structure. The novel spin-labeled A(1)-selective or A(1)/A(2B)-nonselective adenosine receptor antagonists may become useful probes for biophysicochemical investigations of adenosine receptors in their membrane environment.
• Versatile, convenient synthesis of pyrimido[1,2,3-cd]purinediones
  作者：Stefanie Weyler、Alaa M Hayallah、Christa E Müller

  DOI：10.1016/s0040-4020(02)01485-0

  日期：2003.1

  The alkylation of 3-substituted cycloalkylcarboxamido-6-aminouraciI derivatives with 3-bromo-1-propanol followed by ring closure yields 1,3,8-trisubstituted xanthine derivatives bearing a polar hydroxyl group. Use of the more reactive 1,3-dibromopropane or homologous dibromoalkanes for the alkylation reaction results in simultaneous alkylation at N1 and the exocyclic amino group (N-6) yielding imidazo-, pyrimido- and diazepino-pyrimidine derivatives. The pyrimidopyrimidine derivatives can subsequently be cyclised using hexamethyldisilazane at high temperature affording an easy, convenient and general access to tricyclic pyrimido[1,2,3-cd]purinediones. Alternatively, 3-substituted 6-amino-5-benzylideneaminouraciI derivatives can be reacted with 1,3-dibromopropane followed by an oxidative cyclisation using thionyl chloride to obtain the desired tricyclic pyrimido[1,2,3-cd]purinediones, which are sterically fixed analogues of pharmacologically active purine derivatives. (C) 2002 Elsevier Science Ltd. All rights reserved.