8-cyclopentyl-1,3-dipropyl-6-thioxanthine

• 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: 8-cyclopentyl-1,3-dipropyl-6-thioxanthine
• 英文别名: 8-Cyclopentyl-1,3-dipropyl-6-thioxo-1,3,6,7-tetrahydro-purin-2-one；8-cyclopentyl-1,3-dipropyl-6-sulfanylidene-7H-purin-2-one
• 化学式: C₁₆H₂₄N₄OS
• 分子量: 320.459
• InChiKey: GCKBVPYVORUWAC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  84.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  8-环戊烷基-1,3-二丙基黄嘌呤 在 tetraphosphorus decasulfide 作用下， 以 1,4-二氧六环 为溶剂， 反应 5.0h， 以81%的产率得到8-cyclopentyl-1,3-dipropyl-6-thioxanthine
  参考文献：
  名称：

  Sulfur-containing 1,3-dialkylxanthine derivatives as selective antagonists at A1-adenosine receptors

  摘要：

  Sulfur-containing analogues of 8-substituted xanthines were prepared in an effort to increase selectivity or potency as antagonists at adenosine receptors. Either cyclopentyl or various aryl substituents were utilized at the 8-position, because of the association of these groups with high potency at A1-adenosine receptors. Sulfur was incorporated on the purine ring at positions 2 and/or 6, in the 8-position substituent in the form of 2- or 3-thienyl groups, or via thienyl groups separated from an 8-aryl substituent through an amide-containing chain. The feasibility of using the thienyl group as a prosthetic group for selective iodination via its Hg2+ derivative was explored. Receptor selectivity was determined in binding assays using membrane homogenates from rat cortex [( 3H]-N6-(phenylisopropyl)adenosine as radioligand] or striatum [3H]-5'-(N-ethylcarbamoyl)adenosine as radioligand] for A1- and A2-adenosine receptors, respectively. Generally, 2-thio-8-cycloalkylxanthines were at least as A1 selective as the corresponding oxygen analogue. 2-Thio-8-aryl derivatives tended to be more potent at A2 receptors than the oxygen analogue. 8-[4-[(Carboxy-methyl)oxyl] phenyl]-1,3-dipropyl-2-thioxanthine ethyl ester was greater than 740-fold A1 selective.

  DOI：

  10.1021/jm00128a031

文献信息

• US5453426A
  申请人：——

  公开号：US5453426A

  公开（公告）日：1995-09-26
• [EN] SULFER-CONTAINING XANTHINE DERIVATIVES AS ADENOSIN ANTAGONISTS
  申请人：THE UNITED STATES OF AMERICA, as represented by THE SECRETARY, U.S. DEPARTMENT OF COMMERCE

  公开号：WO1990012797A1

  公开（公告）日：1990-11-01

  (EN) Sulfur-containing analogs of 8-substituted xanthines were prepared in an effort to increase selectively or potency as antagonists at adenosine receptors. Either cyclopentyl- or various aryl-substituents were utilized at the 8-position, because of the association of these groups with high potency at A1-adenosine receptors. Sulfur was incorporated on the purine ring at positions 2- and/or 6-, in the 8-position substituent in the form of 2- or 3-thienyl groups, or thienyl groups separated from an 8-aryl substituent through an amide-containing chain. The feasibility of using the thienyl groups as a prosthetic group for selective iodination via its Hg+2 derivative was explored. Receptor selectively was determined in binding assays using membrane homogenates from rat cortex ([3H]N6-phenylisopropyl-adenosine as radioligand) or striatum ([3H]N-ethylcarboxamido-adenosine as radioligand) for A1- and A2-adenosine receptors, respectively. Generally 2-thio-8-cycloalkylxanthines were at least as A1-selective as the corresponding oxygen analog. 2-Thio-8-aryl derivatives tended to be more potent at A2-receptors than the oxygen analog. 1,3-Dipropyl-8-(2-thienyl)-2-thioxanthine was >285-fold A1-selective.(FR) Des analogues de xanthines substituées en position 8 contenant du soufre ont été préparés en vue d'augmenter leur sélectivité ou leur puissance comme antagonistes dans les récepteurs d'adénosine. Des agents de substitution du cyclopentyl ou de l'aryle étaient utilisés en position 8, en raison de l'association de ces groupes avec une puissance élevée dans les récepteurs d'adénosine A1. Le sulfure était incorporé dans l'anneau purinique aux positions 2- et/ou 6-, et en position 8 de substitution sous la forme de groupes thiényle 2- ou 3-, ou de groupes thiényle séparés d'un substituant d'aryle 8 par une chaîne contenant une amide. La faisabilité d'utiliser le groupe thiényle comme groupe de substitution pour iodination sélective via son dérivé Hg+2 a été recherchée. La sélectivité du récepteur a été déterminée par des liaisons d'essai en utilisant des homogénats de membrane provenant du cortex d'un rat ([3H]N6-phénylisopropyl-adénosine comme radioligand) ou striatum ([3H]N-éthylcarboxamido-adénosine comme radioligand) pour respectivement des récepteurs d'adénosine A1 et A2. Généralement, les 2-thio-8- cycloalkylxanthines étaient au moins aussi sélectives de A1 que leur analogue oxygène correspondant. Les dérivés 2-thio-8-aryl avaient tendance à être plus puissants dans les récepteurs A2 que l'analogue oxygène. Le 1,3-dipropyl-8-(2-thiényl)-2-thioxanthène était plus de 285 fois plus efficace comme sélecteur de A1.
• Sulfur-containing 1,3-dialkylxanthine derivatives as selective antagonists at A1-adenosine receptors
  作者：Kenneth A. Jacobson、Leonidas Kiriasis、Suzanne Barone、Barton J. Bradbury、Udai Kammula、Jean Michel Campagne、John W. Daly、John L. Neumeyer、Wolfgang Pfleiderer、Sherrie Secunda

  DOI：10.1021/jm00128a031

  日期：1989.8

  Sulfur-containing analogues of 8-substituted xanthines were prepared in an effort to increase selectivity or potency as antagonists at adenosine receptors. Either cyclopentyl or various aryl substituents were utilized at the 8-position, because of the association of these groups with high potency at A1-adenosine receptors. Sulfur was incorporated on the purine ring at positions 2 and/or 6, in the 8-position substituent in the form of 2- or 3-thienyl groups, or via thienyl groups separated from an 8-aryl substituent through an amide-containing chain. The feasibility of using the thienyl group as a prosthetic group for selective iodination via its Hg2+ derivative was explored. Receptor selectivity was determined in binding assays using membrane homogenates from rat cortex [( 3H]-N6-(phenylisopropyl)adenosine as radioligand] or striatum [3H]-5'-(N-ethylcarbamoyl)adenosine as radioligand] for A1- and A2-adenosine receptors, respectively. Generally, 2-thio-8-cycloalkylxanthines were at least as A1 selective as the corresponding oxygen analogue. 2-Thio-8-aryl derivatives tended to be more potent at A2 receptors than the oxygen analogue. 8-[4-[(Carboxy-methyl)oxyl] phenyl]-1,3-dipropyl-2-thioxanthine ethyl ester was greater than 740-fold A1 selective.