3-benzyl-8-cyclopentyl-1-propylxanthine | 200556-89-4

• 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-benzyl-8-cyclopentyl-1-propylxanthine
• 英文别名: 3-Benzyl-8-cyclopentyl-1-propyl-3,7-dihydro-purine-2,6-dione；3-benzyl-8-cyclopentyl-1-propyl-7H-purine-2,6-dione
• CAS: 200556-89-4
• 化学式: C₂₀H₂₄N₄O₂
• 分子量: 352.436
• InChiKey: WYOIQJXDUHZUAN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  26
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  69.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-benzyl-8-cyclopentyl-1-propylxanthine 在 palladium on activated charcoal sodium hydroxide 、 ammonium formate 、 sodium carbonate 作用下， 以 甲醇 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.5h， 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
• 作为产物：
  描述：

  1-苄基-3-丙基脲 在 sodium dithionite 、 乙酸酐 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 3.75h， 生成 3-benzyl-8-cyclopentyl-1-propylxanthine
  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

• New irreversible adenosine A1 antagonists based on FSCPX
  作者：Anthony R Beauglehole、Stephen P Baker、Peter J Scammells

  DOI：10.1016/s0960-894x(02)00639-x

  日期：2002.11

  FSCPX (1) and its amide analogue (2) have been reported to exhibit potent and selective irreversible antagonism of the A(1) adenosine receptor (A(1)AR) when used in in vitro biological preparations. In order to obtain an irreversible A(1)AR antagonist with improved stability, analogues of FSCPX incorporating the chemoreactive 4-(fluorosulfonyl)phenyl moiety separated from the xanthine pharmacophore

  据报道，在体外生物制剂中使用FSCPX（1）及其酰胺类似物（2）对A（1）腺苷受体（A（1）AR）表现出有效且选择性的不可逆拮抗作用。为了获得具有改善的稳定性的不可逆的A（1）AR拮抗剂，研究了FSCPX的类似物，该类似物结合了化学活性的4-（氟磺酰基）苯基部分，该部分通过酮键与黄嘌呤药效团分开。化合物4a-c对A（1）AR表现出改善的亲和力，并且与A（1）AR的浓度依赖性不可逆结合。
• Fluorosulfonyl-Substituted Xanthines as Selective Irreversible Antagonists for the A₁-Adenosine Receptor
  作者：Anthony R. Beauglehole、Stephen P. Baker、Peter J. Scammells

  DOI：10.1021/jm000181f

  日期：2000.12.1

  FSCPX (1) has been reported to be a potent, selective, and irreversible antagonist for the A(1)-adenosine receptor (AR). To obtain an irreversible A(1)AR antagonist with potentially better stability and to further elucidate the effects of linker structure on the pharmacological characteristics, several new analogues were targeted in which the labile ester linkage of 1 was replaced by more stable functionalities. In particular, alkyl and:amide linkers between the xanthine pharmacophore and the reactive 4-fluorosulfonylphenyl group were explored. The data showed that the chemical composition of the linker affects the affinity and apparent irreversible binding to the A(1)AR. Overall, compound 23b appeared to have the most advantageous characteristics as a potential irreversible ligand for the A(1)AR. These include relatively high affinity for the A(1)AR. as compared to the A(2A)AR, concentration-dependent and selective apparent irreversible binding to the A(1)AR, and ease;of removal of unbound ligand from biological membranes. These :properties indicate that 23b has the potential to be a useful tool for further study of the structure and function of the A(1)AR.
• [EN] ADENOSINE RECEPTOR ANTAGONISTS WITH IMPROVED BIOACTIVITY<br/>[FR] ANTAGONISTES DU RECEPTEUR DE L'ADENOSINE PRESENTANT UNE BIOACTIVITE AMELIOREE
  申请人：UNIVERSITY OF SOUTH FLORIDA

  公开号：WO1999031101A1

  公开（公告）日：1999-06-24

  (EN) Xanthine A1AR antagonist having halogenated N-1 and/or N-3 side chains are provided. The methods for the syntheses of such antagonists are also provided. The methods for using such antagonist labeled with carbon-11, fluorine-18 or isotopes of iodine such as iodine-123 for medical diagnostic imaging of the A1AR in patients are provided. Methods for improving the potency and duration of action of xanthine A1AR antagonist by halogenation of N-1 and N-3 propyl substituents is provided.(FR) L'invention concerne une xanthine, antagoniste du récepteur de l'adénosine A1, et/ou des chaînes latérales de N-3. L'invention traite également de procédés permettant d'effectuer la synthèse de ces antagonistes. L'invention a aussi pour objet des procédés permettant d'utiliser cet antagoniste marqué au carbone-11, au fluor-18 ou des isotopes d'iode tel que l'iode-123 pour l'imagerie diagnostique médicale du récepteur de l'adénosine A1 chez les patients. L'invention traite aussi de procédés permettant d'améliorer la puissance et la durée d'action de la xanthine, antagoniste du récepteur de l'adénosine A1 par halogénation de substituants de propyle N-1 et N-3.
• 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.