3,7-Dimethyl-8-phenyl-1-prop-2-ynyl-3,7-dihydro-purine-2,6-dione | 152529-80-1

• 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: 3,7-Dimethyl-8-phenyl-1-prop-2-ynyl-3,7-dihydro-purine-2,6-dione
• 英文别名: 3,7-dimethyl-8-phenyl-1-prop-2-ynylpurine-2,6-dione
• CAS: 152529-80-1
• 化学式: C₁₆H₁₄N₄O₂
• 分子量: 294.313
• InChiKey: ZAZXEMSNSTVIIF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  58.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  6-氨基-1-甲基尿嘧啶 在 吡啶 、 sodium hydroxide 、 溴 、 碳酸氢钠 、 potassium carbonate 作用下， 以 甲醇 、 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.5h， 生成 3,7-Dimethyl-8-phenyl-1-prop-2-ynyl-3,7-dihydro-purine-2,6-dione
  参考文献：
  名称：

  Synthesis and Structure−Activity Relationships of 3,7-Dimethyl-1-propargylxanthine Derivatives, A_2A-Selective Adenosine Receptor Antagonists

  摘要：

  A series of 8-substituted derivatives of 3,7-dimethyl-1-propargylxanthine (DMPX) was synthesized and investigated as A(2A) adenosine receptor antagonists. Different synthetic strategies for the preparation of DMPX derivatives and analogues were explored. A recently developed synthetic procedure starting from 3-propargyl-5,6-diaminouracil proved to be the method of choice for the preparation of this type of xanthine derivatives. The novel compounds were investigated in radioligand binding studies at the high-affinity adenosine receptor subtypes A(1) and A(2A) and compared with standard A(2A) adenosine receptor antagonists. Structure-activity relationships were analyzed in detail. 8-Styryl-substituted DMPX derivatives were identified that exhibit high affinity and selectivity for A(2A) adenosine receptors, including 8-(m-chlorostyryl)-DMPX (CS-DMPX, K-i A(2A) = 13 nM, 100-fold selective), 8-(m-bromostyryl)-DMPX (BS-DMPX, K-i A(2A) = 8 nM, 146-fold selective), and 8-(3,4-dimethoxystyryl)-DMPX (K-i A(2A) = 15 nM, 167-fold selective). These and other novel compounds are superior to the standard A(2A) adenosine receptor antagonists KF17837 (4) and CSC (5) with respect to A(2A) affinity and/or selectivity.

  DOI：

  10.1021/jm970515+

文献信息

• Synthesis of paraxanthine analogs (1,7-disubstituted xanthines) and other xanthines unsubstituted at the 3-position: structure-activity relationships at adenosine receptors
  作者：Christa E. Mueller、Dan Shi、Malcolm Manning、John W. Daly

  DOI：10.1021/jm00074a015

  日期：1993.10

  paraxanthine analogs (1,7-disubstituted xanthines) and 1,8-disubstituted xanthines, were developed. Silylation of 1-substituted xanthines followed by alkylation at the 7-position provides a facile route to paraxanthine analogs. Regioselective alkylation of tris(trimethylsilyl)-6-aminouracil provides 3-substituted 6-aminouracils, which are converted to 1,8-disubstituted xanthines by standard procedures

  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。
• 8-ALKYNYLXANTHINES AND DERIVATIVES
  申请人：Muller Christa E.

  公开号：US20080221134A1

  公开（公告）日：2008-09-11

  Disclosed are novel compounds of the general formula (Ia), and pharmaceutically acceptable salts, isomers, diastereomers or enantiomers thereof and their use as medicines, for example in the treatment of dopamine-related movement disorders.

  本发明涉及一种新型化合物，其通式为（Ia），以及其药学上可接受的盐、异构体、顺反异构体或对映异构体，以及它们作为药物的用途，例如用于治疗与多巴胺相关的运动障碍。
• US8044061B2
  申请人：——

  公开号：US8044061B2

  公开（公告）日：2011-10-25
• [EN] 8-ETHINYLXANTHINE DERIVATIVES AS SELECTIVE A2A RECEPTOR ANTAGONISTS<br/>[FR] DÉRIVÉS 8-ÉTHYNYLXANTHINE EN TANT QU'ANTAGONISTES SÉLECTIFS DU RÉCEPTEUR 2A
  申请人：SANOL ARZNEI SCHWARZ GMBH

  公开号：WO2008077557A1

  公开（公告）日：2008-07-03

  [EN] Disclosed are novel compounds of the general formula (Ia), and pharmaceutically acceptable salts, isomers, diastereomers or enantiomers thereof (Ia) and their use as medicines, for example in the treatment of dopamine-related movement disorders.
  [FR] La présente invention concerne de nouveaux composés de formule générale (Ia), et leurs sels, isomères, diastéréomères ou enantiomères pharmaceutiquement acceptables ainsi que leur utilisation en tant que médicaments, par exemple dans le traitement de troubles du mouvement liés à la dopamine.
• Synthesis and Structure−Activity Relationships of 3,7-Dimethyl-1-propargylxanthine Derivatives, A_2A-Selective Adenosine Receptor Antagonists
  作者：Christa E. Müller、Uli Geis、Jo Hipp、Ulrike Schobert、Wolfram Frobenius、Maciej Pawłowski、Fumio Suzuki、Jesús Sandoval-Ramírez

  DOI：10.1021/jm970515+

  日期：1997.12.1

  A series of 8-substituted derivatives of 3,7-dimethyl-1-propargylxanthine (DMPX) was synthesized and investigated as A(2A) adenosine receptor antagonists. Different synthetic strategies for the preparation of DMPX derivatives and analogues were explored. A recently developed synthetic procedure starting from 3-propargyl-5,6-diaminouracil proved to be the method of choice for the preparation of this type of xanthine derivatives. The novel compounds were investigated in radioligand binding studies at the high-affinity adenosine receptor subtypes A(1) and A(2A) and compared with standard A(2A) adenosine receptor antagonists. Structure-activity relationships were analyzed in detail. 8-Styryl-substituted DMPX derivatives were identified that exhibit high affinity and selectivity for A(2A) adenosine receptors, including 8-(m-chlorostyryl)-DMPX (CS-DMPX, K-i A(2A) = 13 nM, 100-fold selective), 8-(m-bromostyryl)-DMPX (BS-DMPX, K-i A(2A) = 8 nM, 146-fold selective), and 8-(3,4-dimethoxystyryl)-DMPX (K-i A(2A) = 15 nM, 167-fold selective). These and other novel compounds are superior to the standard A(2A) adenosine receptor antagonists KF17837 (4) and CSC (5) with respect to A(2A) affinity and/or selectivity.