1-propyl-3-(2-hydroxyethyl)-8-cyclopentyl-7H-purine-2,6-dione | 158892-44-5

• 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: 1-propyl-3-(2-hydroxyethyl)-8-cyclopentyl-7H-purine-2,6-dione
• 英文别名: 8-cyclopentyl-3-(2-hydroxyethyl)-1-propyl-7H-purine-2,6-dione
• CAS: 158892-44-5
• 化学式: C₁₅H₂₂N₄O₃
• 分子量: 306.365
• InChiKey: NSMIHNGYQGWREO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  89.5
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  四碘甲烷 、 1-propyl-3-(2-hydroxyethyl)-8-cyclopentyl-7H-purine-2,6-dione 在 三苯基膦 作用下， 以 甲苯 、 乙腈 为溶剂， 生成 8-cyclopentyl-3-(2-iodoethyl)-1-propylxanthine
  参考文献：
  名称：

  Asymmetrically substituted xanthines

  摘要：

  化合物的式子为##STR1## 其中R.sub.1为氢，烷基或炔基，R.sub.2不同且为烷基，炔基，苯基-亚烷基，苯基-烯基，环烷基等，R.sub.3为环烷基，苯基，藿烷等，R.sub.4为氢，甲基，苄基等。

  公开号：

  US05719279A1
• 作为产物：
  描述：

  5,6-diamino-1-benzyl-3-propyl-1H-pyrimidine-2,4-dione 在 palladium on activated charcoal sodium hydroxide 、 ammonium formate 、 sodium carbonate 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.75h， 生成 1-propyl-3-(2-hydroxyethyl)-8-cyclopentyl-7H-purine-2,6-dione
  参考文献：
  名称：

  A₁ Adenosine Receptor Antagonists as Ligands for Positron Emission Tomography (PET) and Single-Photon Emission Tomography (SPET)

  摘要：

  The high affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX) for the A(1) adenosine receptor (A(1)AR) provides a good lead for developing radioligands suitable for positron emission tomography (PET) and single-photon emission tomography (SPET). This study tested the hypothesis that the kinds of chemical modifications made in the synthesis of CPX analogues containing carbon-ii, fluorine-18, or radioiodine will not alter affinity for the A(1)AR. This report describes the synthesis and radioligand binding assays of unlabeled CPX analogues having methyl, 2-methoxyethyl, 2-fluoropropyl, or 3-fluoropropyl substituents, respectively, at either N-1 (13a-d) or N-3 (8a-d) or an (E)-3-iodoprop-2-en-1-yl substituent at N-3 (8f). Compounds 8d,f and 13b,d antagonized the binding of [H-3]CPX to the A(1)AR of rat brain with affinities similar to those of CPX; compound 8c was twice as potent as CPX. Analogues 8a,b and 13a were less potent than CPX, but for each the K-i of antagonism was greater than or equal to 0.5 nM. Attempts to iodinate the 8-(4-hydroxyphenyl) analogue of CPX failed, probably because the xanthine substituent strongly deactivated the phenol toward electrophilic iodination. In summary, several of the modifications of the propyl groups of CPX needed to produce ligands for imaging by PET and SPET preserve or enhance affinity for the A(1)AR.

  DOI：

  10.1021/jm9705465

文献信息

• [DE] UNSYMMETRISCH SUBSTITUIERTE XANTHINE MIT ADENOSINANTAGONISTISCHEN EIGENSCHAFTEN<br/>[EN] ASYMMETRICALLY SUBSTITUTED XANTHINE WITH ADENOSINE-ANTAGONISTIC PROPERTIES<br/>[FR] XANTHINE SUBSTITUEE ASYMETRIQUEMENT AYANT DES PROPRIETES ANTAGONISTES DE L'ADENOSINE
  申请人：BOEHRINGER INGELHEIM KG

  公开号：WO1994003456A1

  公开（公告）日：1994-02-17

  (DE) Die vorliegende Erfindung betrifft neue Xanthin-Derivate, Verfahren zu ihrer Herstellung und ihre Verwendung als Arzneimittel und ihre Verwendung als Zwischenverbindungen.(EN) New xanthine derivatives, a process for preparing the same and their use as medicaments are disclosed, as well as their use as intermediate compounds.(FR) L'invention concerne de nouveaux dérivés de xanthine, leur procédé de fabrication et leur utilisation comme médicaments, ainsi que leur utilisation comme composés intermédiaires.

  该发明涉及新型蒽醌衍生物、制备它们的方法以及它们用作药品和中间化合物的用途。...(此处截稿，完整翻译未提供)
• [DE] SYNERGISTISCHE KOMBINATION ZUR BEHANDLUNG DEGENERATIVER ALTERSERKRANKUNGEN, ENTHALTEND EINEN ADENOSIN-ANTAGONISTEN UND EIN CHOLINOMIMETIKUM<br/>[EN] SYNERGISTIC COMBINATION FOR THE THERAPY OF DEGENERATIVE AGEING DISEASES CONTAINING AN ADENOSINE ANTAGONIST AND A CHOLINOMIMETIC<br/>[FR] COMBINAISON SYNERGIQUE POUR LE TRAITEMENT DE MALADIES DEGENERATIVES LIEES AU VIEILLISSEMENT, CONTENANT UN ANTAGONISTE DE L'ADENOSINE ET UN CHOLINOMIMETIQUE
  申请人：BOEHRINGER INGELHEIM KG

  公开号：WO1994009787A1

  公开（公告）日：1994-05-11

  (DE) Die Erfindung betrifft eine synergistische Wirkstoffkombination für die symptomatische Therapie degenerativer Alterserkrankungen. Die Kombination enthält einen Adenosin-Antagonisten (A) und eine cholinomimetisch wirkende Substanz (B). B ist bevorzugt eine Verbindung der Formel (I) oder (II) oder (III) oder (IV). A ist bevorzugt eine Verbindung der Formel (V) oder (VI), worin n, R, R2 und R3 die in der Beschreibung angegebene Bedeutung haben.(EN) A synergistic active substance combination is disclosed for the symptomatic therapy of degenerative ageing diseases. The combination contains an adenosine antagonist (A) and a substance (B) having a cholinomimetic action. B is preferably a compound having the formulas (I) or (II) or (III) or (IV), and A is preferably a compound having the formulas (V) or (VI), in which n, R, R2 and R3 have the meaning given in the description.(FR) L'invention concerne une combinaison synergique de principes actifs pour le traitement symptomatique de maladies dégénératives liées au vieillissement. La combinaison contient un antagoniste de l'adénosine (A) et un principe actif cholinomimétique (B). B est de préférence un composé des formules (I) ou (II) ou (III) ou (IV). A est de préférence un composé des formules (V) ou (VI), où n, R, R2 et R3 ont la notation mentionnée dans la description.

  该发明涉及一种协同作用的活性组分组合，用于渐进式疾病退行性老年病的对症治疗。该组合包含腺苷拮抗剂(A)和具有胆碱类似效作用的活性物质(B)。B更倾向于具有化学式(I)、(II)、(III)或(IV)的形式。A更倾向于具有化学式(V)或(VI)的化合物，在这些情况下，n、R、R2和R3具有描述中给出的意义。
• UNSYMMETRISCH SUBSTITUIERTE XANTHINE MIT ADENOSINANTAGONISTISCHEN EIGENSCHAFTEN
  申请人：BOEHRINGER INGELHEIM KG

  公开号：EP0654033A1

  公开（公告）日：1995-05-24
• US5719279A
  申请人：——

  公开号：US5719279A

  公开（公告）日：1998-02-17
• A₁ Adenosine Receptor Antagonists as Ligands for Positron Emission Tomography (PET) and Single-Photon Emission Tomography (SPET)
  作者：Marcus H. Holschbach、Thomas Fein、Christof Krummeich、Robert G. Lewis、Walter Wutz、Ulrich Schwabe、Dieter Unterlugauer、Ray A. Olsson

  DOI：10.1021/jm9705465

  日期：1998.2.1

  The high affinity of 8-cyclopentyl-1,3-dipropylxanthine (CPX) for the A(1) adenosine receptor (A(1)AR) provides a good lead for developing radioligands suitable for positron emission tomography (PET) and single-photon emission tomography (SPET). This study tested the hypothesis that the kinds of chemical modifications made in the synthesis of CPX analogues containing carbon-ii, fluorine-18, or radioiodine will not alter affinity for the A(1)AR. This report describes the synthesis and radioligand binding assays of unlabeled CPX analogues having methyl, 2-methoxyethyl, 2-fluoropropyl, or 3-fluoropropyl substituents, respectively, at either N-1 (13a-d) or N-3 (8a-d) or an (E)-3-iodoprop-2-en-1-yl substituent at N-3 (8f). Compounds 8d,f and 13b,d antagonized the binding of [H-3]CPX to the A(1)AR of rat brain with affinities similar to those of CPX; compound 8c was twice as potent as CPX. Analogues 8a,b and 13a were less potent than CPX, but for each the K-i of antagonism was greater than or equal to 0.5 nM. Attempts to iodinate the 8-(4-hydroxyphenyl) analogue of CPX failed, probably because the xanthine substituent strongly deactivated the phenol toward electrophilic iodination. In summary, several of the modifications of the propyl groups of CPX needed to produce ligands for imaging by PET and SPET preserve or enhance affinity for the A(1)AR.