1,3-dipropyl-8-(trans-4-carboxycyclohexyl)xanthine | 127946-00-3

• 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-(trans-4-carboxycyclohexyl)xanthine
• CAS: 127946-00-3
• 化学式: C₁₈H₂₆N₄O₄
• 分子量: 362.429
• InChiKey: ZVVKJJVTWDPGLA-HAQNSBGRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.06
• 重原子数：
  26.0
• 可旋转键数：
  6.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  109.98
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1,3-dipropyl-8-(trans-4-carboxycyclohexyl)xanthine 在 硼烷四氢呋喃络合物 、 溶剂黄146 作用下， 以 四氢呋喃 为溶剂， 反应 3.0h， 以83%的产率得到
  参考文献：
  名称：

  Potent and Orally Bioavailable 8-Bicyclo[2.2.2]octylxanthines as Adenosine A₁ Receptor Antagonists

  摘要：

  In the search for a selective adenosine A(1) receptor antagonist with greater aqueous solubility than the compounds currently in clinical trials as diuretics, a series of 1,4- substituted 8-cyclohexyl and 8-bicyclo-[2.2.2] octylxanthines were investigated. The binding affinities of a variety of cyclohexyl and bicyclo[2.2.2]octylxanthines for the rat and human adenosine A(1), A(2A), A(2B), and A(3) receptors are presented. Bicyclo[ 2.2.2] octylxanthine 16 exhibited good pharmaceutical properties and in vivo activity in a rat diuresis model (ED50=0.3 mg/ kg po). Optimization of the bridgehead substituent led to propionic acid 29 ( BG9928), which retained high potency ( hA(1), K-i=7 nM) and selectivity for the adenosine A1 receptor (915-fold versus adenosine A2A receptor; 12-fold versus adenosine A2B receptor) with improved oral efficacy in the rat diuresis model (ED50=0.01 mg/ kg) as well as high oral bioavailability in rat, dog, and cynomolgus monkey.

  DOI：

  10.1021/jm0605381
• 作为产物：
  描述：

  Trans-1,4-Cyclohexanedicarboxylic Acid Monomethyl Ester 在 sodium hydroxide 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 6.0h， 生成 1,3-dipropyl-8-(trans-4-carboxycyclohexyl)xanthine
  参考文献：
  名称：

  8-环烷基-1,3-二丙基黄嘌呤作为腺苷受体拮抗剂的构效关系。

  摘要：

  8-取代的黄嘌呤目前代表最有效的腺苷-受体拮抗剂。制备了一系列8-取代的1，3-二丙基黄嘌呤，并确定了它们分别作为人血小板和大鼠脂肪细胞的A1和A2腺苷受体拮抗剂的效力。没有研究药物能像A1腺苷受体拮抗剂那样与8-环戊基-1,3-二丙基黄嘌呤一样有效，但是8-（2-甲基环丙基）-1,3-二丙基黄嘌呤比A1腺苷受体的效力至少强1000倍。 A1比A2的腺苷受体高。虽然8-环烷基部分上的大多数取代都导致抑制A1和A2腺苷受体，8- [反式-4-（乙酰氨基甲基）环己基] -1的效力降低，

  DOI：

  10.1021/jm00169a012

文献信息

• Structure-activity relationships of 8-cycloalkyl-1,3-dipropylxanthines as antagonists of adenosine receptors
  作者：T. Katsushima、L. Nieves、J. N. Wells

  DOI：10.1021/jm00169a012

  日期：1990.7

  least 1000-fold more potent as an antagonist of A1 than of A2 adenosine receptors. While most substitutions on the 8-cycloalkyl moiety caused decreased potency to inhibit both A1 and A2 adenosine receptors, 8-[trans-4-(acetamidomethyl)cyclohexyl]-1,3-dipropylxanthine was nearly equipotent as an antagonist of the two receptors and appeared to be the most potent antagonist of A2 adenosine receptors reported

  8-取代的黄嘌呤目前代表最有效的腺苷-受体拮抗剂。制备了一系列8-取代的1，3-二丙基黄嘌呤，并确定了它们分别作为人血小板和大鼠脂肪细胞的A1和A2腺苷受体拮抗剂的效力。没有研究药物能像A1腺苷受体拮抗剂那样与8-环戊基-1,3-二丙基黄嘌呤一样有效，但是8-（2-甲基环丙基）-1,3-二丙基黄嘌呤比A1腺苷受体的效力至少强1000倍。 A1比A2的腺苷受体高。虽然8-环烷基部分上的大多数取代都导致抑制A1和A2腺苷受体，8- [反式-4-（乙酰氨基甲基）环己基] -1的效力降低，
• Potent and Orally Bioavailable 8-Bicyclo[2.2.2]octylxanthines as Adenosine A₁ Receptor Antagonists
  作者：William F. Kiesman、Jin Zhao、Patrick R. Conlon、James E. Dowling、Russell C. Petter、Frank Lutterodt、Xiaowei Jin、Glenn Smits、Mary Fure、Andrew Jayaraj、John Kim、Gail Sullivan、Joel Linden

  DOI：10.1021/jm0605381

  日期：2006.11.30

  In the search for a selective adenosine A(1) receptor antagonist with greater aqueous solubility than the compounds currently in clinical trials as diuretics, a series of 1,4- substituted 8-cyclohexyl and 8-bicyclo-[2.2.2] octylxanthines were investigated. The binding affinities of a variety of cyclohexyl and bicyclo[2.2.2]octylxanthines for the rat and human adenosine A(1), A(2A), A(2B), and A(3) receptors are presented. Bicyclo[ 2.2.2] octylxanthine 16 exhibited good pharmaceutical properties and in vivo activity in a rat diuresis model (ED50=0.3 mg/ kg po). Optimization of the bridgehead substituent led to propionic acid 29 ( BG9928), which retained high potency ( hA(1), K-i=7 nM) and selectivity for the adenosine A1 receptor (915-fold versus adenosine A2A receptor; 12-fold versus adenosine A2B receptor) with improved oral efficacy in the rat diuresis model (ED50=0.01 mg/ kg) as well as high oral bioavailability in rat, dog, and cynomolgus monkey.