1,3-di-n-hexylxanthine | 111671-82-0

• 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-di-n-hexylxanthine
• 英文别名: 1,3-Dihexylxanthine；1,3-Dihexyl-3,7-dihydro-1H-purine-2,6-dione；1,3-dihexyl-7H-purine-2,6-dione
• CAS: 111671-82-0
• 化学式: C₁₇H₂₈N₄O₂
• 分子量: 320.435
• InChiKey: MUGSATKSDJICNS-UHFFFAOYSA-N

物化性质

• 沸点：
  511.6±42.0 °C(Predicted)
• 密度：
  1.104±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  23
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 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：

  1,3-di-n-hexylxanthine 在 ruthenium trichloride 、 sodium periodate 、 三氯硅烷 、 左旋樟脑磺酸 、 氨 、 水 、 potassium nonaflate 作用下， 以 二氯甲烷 、 氯仿 、 乙腈 为溶剂， 反应 155.67h， 生成 1,3-di-n-hexylxanthine 7-(2,3-O-isopropylidene)-β-D-ribofuronic acid
  参考文献：
  名称：

  Selective Ligands for Rat A3 Adenosine Receptors: Structure-Activity Relationships of 1,3-Dialkylxanthine 7-Riboside Derivatives

  摘要：

  1,3-Dibutylxanthine 7-riboside has been found to be a partial agonist at A(3) adenosine receptors (van Galen et al. Mol. Pharmacol. 1994, 45, 1101-1111). 1,3-Dialkylxanthine 7-riboside analogues modified at the 1-, 3-, and 8-purine positions and at the ribose 5'-position were synthesized. The nucleoside analogues were examined for affinity in radioligand binding assays at rat brain A(3) adenosine receptors stably expressed in CHO cells, using the radioligand [[I-125]-4-amino- 3-iodobenzyl]adenosine-5'-N-methyluronamide (AB-MECA). Affinity was assayed at rat brain A(1) and A(2a) receptors using [H-3]PIA and [H-3]CGS 21680, respectively. The affinity of xanthine 7-ribosides at A(3) receptors depended on the 1,3-dialkyl substituents in the order: Pent greater than or equal to. Bu >> Hx > Pr approximate to Me. 1,3-Dipentylxanthine 7-riboside was slightly selective for A(3) receptors (2-fold vs A(1) and 10-fold vs A(2a)). 8-Methoxy substitution was tolerated at A(3) receptors. 2-Thio vs 2-oxo substitution increased potency at all three subtypes and slightly increased A(3) vs A(1) selectivity. The 5'-uronamide modification, which was previously found to enhance A(3) selectivity in N-6-benzyladenosine derivatives, was also incorporated into the xanthine 7-ribosides, with similar results. The affinity of 1,3-dialkylxanthine 7-riboside 5'-uronamides at A(3) receptors depended on the N-alkyluronamide substituent in the order: MeNH > EtNH >> NH2 >> Me(2)N. Affinity of the 5'-uronamides at A(3) receptors was dependent on the 1,3-dialkyl substitution in the order: Bu > Pent > Hex. 1,3-Dibutylxanthine 7-riboside 5'-N-methylcarboxamide, with a K-i value of 229 nM at A(3) receptors, was 160-fold selective for rat A(3) vs A(1) receptors and > 400-fold selective vs A(2a) receptors. This derivative acted as a full agonist in the A(3) receptor-mediated inhibition of adenylate cyclase.

  DOI：

  10.1021/jm00049a021

文献信息

• A3 adenosine receptor agonists
  申请人：The United States of America as represented by the Department of Health

  公开号：US05773423A1

  公开（公告）日：1998-06-30

  The present invention provides N.sup.6 -benzyladenosine-5'-N-uronamide and related substituted compounds, particularly those containing substituents on the benzyl and/or uronamide groups, and modified xanthine ribosides, as well as pharmaceutical compositions containing such compounds. The present invention also provides a method of selectively activating an A.sub.3 adenosine receptor in a mammal, which method comprises acutely or chronically administering to a mammal in need of selective activation of its A.sub.3 adenosine receptor a therapeutically effective amount of a compound which binds with the A.sub.3 receptor so as to stimulate an A.sub.3 receptor-dependent response.

  本发明提供了N.sup.6-苄基腺苷-5'-N-醛脲和相关的取代化合物，特别是那些在苄基和/或醛脲基团上含有取代基的化合物，以及修饰的黄嘌呤核糖苷，以及含有这些化合物的药物组合物。本发明还提供了一种在哺乳动物中选择性激活A.sub.3腺苷受体的方法，该方法包括向需要选择性激活其A.sub.3腺苷受体的哺乳动物急性或慢性地给予与A.sub.3受体结合的化合物的治疗有效量，以刺激A.sub.3受体依赖的反应。
• A 3 ADENOSINE RECEPTOR AGONISTS
  申请人：THE UNITED STATES OF AMERICA, as represented by the Secretary of the Department of Health and Human Services

  公开号：EP0708781A1

  公开（公告）日：1996-05-01
• US5773423A
  申请人：——

  公开号：US5773423A

  公开（公告）日：1998-06-30
• [EN] A3 ADENOSINE RECEPTOR AGONISTS<br/>[FR] AGONISTES DU RECEPTEUR DE L'ADENOSINE A3
  申请人：THE UNITED STATES OF AMERICA, represented by THE SECRETARY, DEPARTMENT OF HEALTH AND HUMAN SERVICES

  公开号：WO1995002604A1

  公开（公告）日：1995-01-26

  (EN) The present invention provides N6-benzyladenosine-5'-N-uronamide and related substituted compounds, particularly those containing substituents on the benzyl and/or uronamide groups, and modified xanthine ribosides, as well as pharmaceutical compositions containing such compounds. The present invention also provides a method of selectively activating an A3 adenosine receptor in a mammal, which method comprises acutely or chronically administering to a mammal in need of selective activation of its A3 adenosine receptor a therapeutically effective amount of a compound which binds with the A3 receptor so as to stimulate and A3 receptor-dependent response.(FR) La présente invention concerne N6-benzyladénosine-5'-N-uronamide et les composés connexes substitués, notamment ceux contenant des substituants se trouvant sur les groupes benzyl et/ou uronamides, et des ribosides de xanthine modifiés, ainsi que des compositions pharmaceutiques contenant ces composés. La présente invention concerne également un procédé d'activation sélective d'un récepteur de l'adénosine A3 chez un mammifère. Ce procédé consiste à administrer, en phase aiguë ou à l'état chronique, à un mammifère nécessitant l'activation sélective de son récepteur d'adénosine A3, une quantité thérapeutiquement efficace d'un composé qui se fixe au récepteur de A3 de façon à stimuler une réponse dépendant du récepteur de A3.
• Selective Ligands for Rat A3 Adenosine Receptors: Structure-Activity Relationships of 1,3-Dialkylxanthine 7-Riboside Derivatives
  作者：Hea Ok Kim、Xiao-duo Ji、Neli Melman、Mark E. Olah、Gary L. Stiles、Kenneth A. Jacobson

  DOI：10.1021/jm00049a021

  日期：1994.11

  1,3-Dibutylxanthine 7-riboside has been found to be a partial agonist at A(3) adenosine receptors (van Galen et al. Mol. Pharmacol. 1994, 45, 1101-1111). 1,3-Dialkylxanthine 7-riboside analogues modified at the 1-, 3-, and 8-purine positions and at the ribose 5'-position were synthesized. The nucleoside analogues were examined for affinity in radioligand binding assays at rat brain A(3) adenosine receptors stably expressed in CHO cells, using the radioligand [[I-125]-4-amino- 3-iodobenzyl]adenosine-5'-N-methyluronamide (AB-MECA). Affinity was assayed at rat brain A(1) and A(2a) receptors using [H-3]PIA and [H-3]CGS 21680, respectively. The affinity of xanthine 7-ribosides at A(3) receptors depended on the 1,3-dialkyl substituents in the order: Pent greater than or equal to. Bu >> Hx > Pr approximate to Me. 1,3-Dipentylxanthine 7-riboside was slightly selective for A(3) receptors (2-fold vs A(1) and 10-fold vs A(2a)). 8-Methoxy substitution was tolerated at A(3) receptors. 2-Thio vs 2-oxo substitution increased potency at all three subtypes and slightly increased A(3) vs A(1) selectivity. The 5'-uronamide modification, which was previously found to enhance A(3) selectivity in N-6-benzyladenosine derivatives, was also incorporated into the xanthine 7-ribosides, with similar results. The affinity of 1,3-dialkylxanthine 7-riboside 5'-uronamides at A(3) receptors depended on the N-alkyluronamide substituent in the order: MeNH > EtNH >> NH2 >> Me(2)N. Affinity of the 5'-uronamides at A(3) receptors was dependent on the 1,3-dialkyl substitution in the order: Bu > Pent > Hex. 1,3-Dibutylxanthine 7-riboside 5'-N-methylcarboxamide, with a K-i value of 229 nM at A(3) receptors, was 160-fold selective for rat A(3) vs A(1) receptors and > 400-fold selective vs A(2a) receptors. This derivative acted as a full agonist in the A(3) receptor-mediated inhibition of adenylate cyclase.