1,3-Dipropyl-8-thiophen-2-yl-3,7-dihydro-purine-2,6-dione | 121542-93-6

• 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: 1,3-Dipropyl-8-thiophen-2-yl-3,7-dihydro-purine-2,6-dione
• 英文别名: 1,3-dipropyl-8-thiophen-2-yl-7H-purine-2,6-dione
• CAS: 121542-93-6
• 化学式: C₁₅H₁₈N₄O₂S
• 分子量: 318.4
• InChiKey: PQZQXCPOCQBALR-UHFFFAOYSA-N

物化性质

• 熔点：
  272-274 °C
• 沸点：
  550.0±48.0 °C(Predicted)
• 密度：
  1.295±0.06 g/cm3(Predicted)

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：
  0.4
• 拓扑面积：
  97.5
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  1,3-二丙基-6-氨基脲嘧啶 在 palladium on activated charcoal 氢气 、 溶剂黄146 、 sodium nitrite 、 偶氮二甲酸二乙酯 作用下， 以 乙二醇二甲醚 、 乙醇 、 水 为溶剂， 90.0 ℃ 、413.69 kPa 条件下， 反应 24.5h， 生成 1,3-Dipropyl-8-thiophen-2-yl-3,7-dihydro-purine-2,6-dione
  参考文献：
  名称：

  1,3,8-三取代的黄嘌呤。取代模式对腺苷受体A1 / A2亲和力的影响。

  摘要：

  一系列11个8-取代的黄嘌呤，在1和3位上具有三个不同的取代模式（模式a（R1 = R3 = CH2CH2CH3），b（R1 = CH2CH2CH3，R3 = CH3）和c（R1 = CH3，制备R 3 ＝ CH 2 CH 2 CH 3）]。评估这些化合物与腺苷A1和A2受体结合的亲和力和选择性。在A1受体上具有最大亲和力的化合物具有1,3取代模式a。除了一个例外，具有模式a的化合物在A2受体上的结合力也最强。但是，几种具有模式c的化合物在A2受体上与那些具有模式a的化合物等价。此外，这些8取代的黄嘌呤的1和3位上的取代基对于确定与A1受体的最大亲和力同样重要，而3位的取代基比1位的取代基对A2受体的效力更重要。结果，可以通过选择1-位和3-位取代基来最大化对A1受体的选择性。然而，以最大的A1选择性所需要的R1 / R3取代模式也以不完全理解的方式取决于8位的取代基。

  DOI：

  10.1021/jm00108a029

文献信息

• 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.
• 8-Polycycloalkyl-1,3-dipropylxanthines as potent and selective antagonists for A1-adenosine receptors
  作者：Junichi Shimada、Fumio Suzuki、Hiromi Nonaka、Akio Ishii

  DOI：10.1021/jm00083a018

  日期：1992.3

  With the aim of characterizing the hydrophobic interactions between xanthines and the A1 receptor site, 1,3-dipropyl-8-substituted xanthines were synthesized. Introduction of a quaternary carbon and the conformationally restricted cyclopentyl moiety into the 8-position of xanthines enhanced the adenosine A1 antagonism. 1,3-Dipropyl-8-(3-noradamantyl)xanthine (42) was identified to be a selective and the most potent A1 receptor antagonist reported to date. Under our structure-activity relationship, the 8-substituent of xanthine antagonists and the N6-substituent of adenosine agonists appears to bind to the same region of the A1 receptor.
• KUFNER-MUHL, ULRIKE;WEBER, KARL-HEINZ;WALTHER, GERHARD;STRANSKY, WERNER;E+
  作者：KUFNER-MUHL, ULRIKE、WEBER, KARL-HEINZ、WALTHER, GERHARD、STRANSKY, WERNER、E+

  DOI：——

  日期：——
• ERICKSON, RONALD H.;HINER, ROGER N.;FEENEY, SCOTT W.;BLAKE, PAUL R.;RZESZ+, J. MED. CHEM., 34,(1991) N, C. 1431-1435
  作者：ERICKSON, RONALD H.、HINER, ROGER N.、FEENEY, SCOTT W.、BLAKE, PAUL R.、RZESZ+

  DOI：——

  日期：——
• 1,3,8-Trisubstituted xanthines. Effects of substitution pattern upon adenosine receptor A1/A2 affinity
  作者：Ronald H. Erickson、Roger N. Hiner、Scott W. Feeney、Paul R. Blake、Waclaw J. Rzeszotarski、Rickey P. Hicks、Diane G. Costello、Mary E. Abreu

  DOI：10.1021/jm00108a029

  日期：1991.4

  8-substituted xanthines were equally important for determining maximum affinity to the A1 receptor, while the substituent at the 3-position is more important than the substituent at the 1-position for potency at the A2 receptor. As a result of this, it is possible to maximize selectivity for the A1 receptor by choice of the 1- and 3-position substituents. However, the R1/R3 substitution pattern required

  一系列11个8-取代的黄嘌呤，在1和3位上具有三个不同的取代模式（模式a（R1 = R3 = CH2CH2CH3），b（R1 = CH2CH2CH3，R3 = CH3）和c（R1 = CH3，制备R 3 ＝ CH 2 CH 2 CH 3）]。评估这些化合物与腺苷A1和A2受体结合的亲和力和选择性。在A1受体上具有最大亲和力的化合物具有1,3取代模式a。除了一个例外，具有模式a的化合物在A2受体上的结合力也最强。但是，几种具有模式c的化合物在A2受体上与那些具有模式a的化合物等价。此外，这些8取代的黄嘌呤的1和3位上的取代基对于确定与A1受体的最大亲和力同样重要，而3位的取代基比1位的取代基对A2受体的效力更重要。结果，可以通过选择1-位和3-位取代基来最大化对A1受体的选择性。然而，以最大的A1选择性所需要的R1 / R3取代模式也以不完全理解的方式取决于8位的取代基。