1-butyl-8-[4-(cyanomethyl)phenyl]xanthine | 409344-84-9

• 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-butyl-8-[4-(cyanomethyl)phenyl]xanthine
• 英文别名: 2-[4-(1-Butyl-2,6-dioxo-3,7-dihydropurin-8-yl)phenyl]acetonitrile
• CAS: 409344-84-9
• 化学式: C₁₇H₁₇N₅O₂
• 分子量: 323.354
• InChiKey: UFQRMJUUVFHWTM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1-butyl-8-[4-(cyanomethyl)phenyl]xanthine 在 硫酸 作用下， 反应 6.0h， 以76%的产率得到1-butyl-8-[4-(carboxymethyl)phenyl]xanthine
  参考文献：
  名称：

  1,8-Disubstituted Xanthine Derivatives:  Synthesis of Potent A_2B-Selective Adenosine Receptor Antagonists

  摘要：

  3-Unsubstituted xanthine derivatives bearing a cyclopentyl or a phenyl residue in the 8-position were synthesized and developed as A(2)B adenosine receptor antagonists. Compounds bearing polar substituents were prepared to obtain water-soluble derivatives. 1-Alkyl-8-phenylxanthine derivatives were found to exhibit high affinity for A(2B) adenosine receptors (ARs). 1,8-Disubstituted xanthine derivatives were equipotent to or more potent than 1,3,8-trisubstituted xanthines at A(2B) ARs, but generally less potent at A(1) and A(2A), and much less potent at A(3) ARs. Thus, the new compounds exhibited increased A2B selectivity versus all other AR subtypes. 9-Deazaxanthines (pyrrolo[2,3-d]pyrimidindiones) appeared to be less potent at A(2B) ARs than the corresponding xanthine derivatives. 1-Propyl-8-p-sulfophenylxanthiiie (17) was the most selective compound of the present series, exhibiting a K-i value of 53 nM at human A(2B) ARs and showing greater than 180-fold selectivity versus human A, ARs. Compound 17 was also highly selective versus rat A, ARs (41-fold) and versus the other human AR subtypes (A(2A) > 400-fold and A3 > 180-fold). The compound is highly water-soluble due to its sulfonate function. 1-Butyl-8-p-carboxyphenylxanthine (10), another polar analogue bearing a carboxylate function, exhibited a K-i value of 24 nM for A(2B) ARs, 49-fold selectivity versus human and 20-fold selectivity versus rat A, ARs, and greater than 150-fold selectivity versus human A2A and A3 ARs. 8-[4-(2-Hydroxyethylamino)-2-oxoethoxy)phenyl]-1-propylxanthine (29) and 1-butyl-8-[4(4-benzyl)piperazino-2-oxoethoxy)phenyl]xanthine (35) were among the most potent A(2B) antagonists showing K-i values at A(2B) ARs of 1 nM, 57-fold (29) and 94-fold (35) selectivity versus human A(1), ca. 30-fold selectivity versus rat A(1), and greater than 400-fold selectivity versus human A(2A) and A(3) ARs. The new potent, selective, water-soluble A(2B) antagonists may be useful research tools for investigating A(2B) receptor function.

  DOI：

  10.1021/jm011049y
• 作为产物：
  描述：

  4-(氰甲基)苯甲酸 在 硫酸氢铵 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 六甲基二硅氮烷 作用下， 以 甲醇 、 水 为溶剂， 反应 50.0h， 生成 1-butyl-8-[4-(cyanomethyl)phenyl]xanthine
  参考文献：
  名称：

  1,8-Disubstituted Xanthine Derivatives:  Synthesis of Potent A_2B-Selective Adenosine Receptor Antagonists

  摘要：

  3-Unsubstituted xanthine derivatives bearing a cyclopentyl or a phenyl residue in the 8-position were synthesized and developed as A(2)B adenosine receptor antagonists. Compounds bearing polar substituents were prepared to obtain water-soluble derivatives. 1-Alkyl-8-phenylxanthine derivatives were found to exhibit high affinity for A(2B) adenosine receptors (ARs). 1,8-Disubstituted xanthine derivatives were equipotent to or more potent than 1,3,8-trisubstituted xanthines at A(2B) ARs, but generally less potent at A(1) and A(2A), and much less potent at A(3) ARs. Thus, the new compounds exhibited increased A2B selectivity versus all other AR subtypes. 9-Deazaxanthines (pyrrolo[2,3-d]pyrimidindiones) appeared to be less potent at A(2B) ARs than the corresponding xanthine derivatives. 1-Propyl-8-p-sulfophenylxanthiiie (17) was the most selective compound of the present series, exhibiting a K-i value of 53 nM at human A(2B) ARs and showing greater than 180-fold selectivity versus human A, ARs. Compound 17 was also highly selective versus rat A, ARs (41-fold) and versus the other human AR subtypes (A(2A) > 400-fold and A3 > 180-fold). The compound is highly water-soluble due to its sulfonate function. 1-Butyl-8-p-carboxyphenylxanthine (10), another polar analogue bearing a carboxylate function, exhibited a K-i value of 24 nM for A(2B) ARs, 49-fold selectivity versus human and 20-fold selectivity versus rat A, ARs, and greater than 150-fold selectivity versus human A2A and A3 ARs. 8-[4-(2-Hydroxyethylamino)-2-oxoethoxy)phenyl]-1-propylxanthine (29) and 1-butyl-8-[4(4-benzyl)piperazino-2-oxoethoxy)phenyl]xanthine (35) were among the most potent A(2B) antagonists showing K-i values at A(2B) ARs of 1 nM, 57-fold (29) and 94-fold (35) selectivity versus human A(1), ca. 30-fold selectivity versus rat A(1), and greater than 400-fold selectivity versus human A(2A) and A(3) ARs. The new potent, selective, water-soluble A(2B) antagonists may be useful research tools for investigating A(2B) receptor function.

  DOI：

  10.1021/jm011049y

文献信息

• 1,8-Disubstituted Xanthine Derivatives:  Synthesis of Potent A_2B-Selective Adenosine Receptor Antagonists
  作者：Alaa M. Hayallah、Jesús Sandoval-Ramírez、Ulrike Reith、Ulrike Schobert、Birgit Preiss、Britta Schumacher、John W. Daly、Christa E. Müller

  DOI：10.1021/jm011049y

  日期：2002.3.1

  3-Unsubstituted xanthine derivatives bearing a cyclopentyl or a phenyl residue in the 8-position were synthesized and developed as A(2)B adenosine receptor antagonists. Compounds bearing polar substituents were prepared to obtain water-soluble derivatives. 1-Alkyl-8-phenylxanthine derivatives were found to exhibit high affinity for A(2B) adenosine receptors (ARs). 1,8-Disubstituted xanthine derivatives were equipotent to or more potent than 1,3,8-trisubstituted xanthines at A(2B) ARs, but generally less potent at A(1) and A(2A), and much less potent at A(3) ARs. Thus, the new compounds exhibited increased A2B selectivity versus all other AR subtypes. 9-Deazaxanthines (pyrrolo[2,3-d]pyrimidindiones) appeared to be less potent at A(2B) ARs than the corresponding xanthine derivatives. 1-Propyl-8-p-sulfophenylxanthiiie (17) was the most selective compound of the present series, exhibiting a K-i value of 53 nM at human A(2B) ARs and showing greater than 180-fold selectivity versus human A, ARs. Compound 17 was also highly selective versus rat A, ARs (41-fold) and versus the other human AR subtypes (A(2A) > 400-fold and A3 > 180-fold). The compound is highly water-soluble due to its sulfonate function. 1-Butyl-8-p-carboxyphenylxanthine (10), another polar analogue bearing a carboxylate function, exhibited a K-i value of 24 nM for A(2B) ARs, 49-fold selectivity versus human and 20-fold selectivity versus rat A, ARs, and greater than 150-fold selectivity versus human A2A and A3 ARs. 8-[4-(2-Hydroxyethylamino)-2-oxoethoxy)phenyl]-1-propylxanthine (29) and 1-butyl-8-[4(4-benzyl)piperazino-2-oxoethoxy)phenyl]xanthine (35) were among the most potent A(2B) antagonists showing K-i values at A(2B) ARs of 1 nM, 57-fold (29) and 94-fold (35) selectivity versus human A(1), ca. 30-fold selectivity versus rat A(1), and greater than 400-fold selectivity versus human A(2A) and A(3) ARs. The new potent, selective, water-soluble A(2B) antagonists may be useful research tools for investigating A(2B) receptor function.