2-Methyl-6-phenyl-4-((E)-styryl)-pyridine-3,5-dicarboxylic acid diethyl ester | 185222-94-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 2-Methyl-6-phenyl-4-((E)-styryl)-pyridine-3,5-dicarboxylic acid diethyl ester
• 英文别名: diethyl 2-methyl-6-phenyl-4-[(E)-2-phenylethenyl]pyridine-3,5-dicarboxylate
• CAS: 185222-94-0
• 化学式: C₂₆H₂₅NO₄
• 分子量: 415.489
• InChiKey: TVZNWOVBAQXKHS-WUKNDPDISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.6
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  65.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  3,5-吡啶二羧酸,1,4-二氢-2-甲基-6-苯基-4-[(1E)-2-苯基乙烯基]-,二乙基酯 在 四氯苯醌 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以29.8%的产率得到2-Methyl-6-phenyl-4-((E)-styryl)-pyridine-3,5-dicarboxylic acid diethyl ester
  参考文献：
  名称：

  6-Phenyl-1,4-dihydropyridine Derivatives as Potent and Selective A₃ Adenosine Receptor Antagonists

  摘要：

  An approach to designing dihydropyridines that bind to adenosine receptors without binding to L-type calcium channels has been described. 1,4-Dihydropyridine derivatives substituted with beta-styryl or phenylethynyl groups at the 4-position and aryl groups at the 6-position were synthesized and found to be selective for human A(3) receptors. Combinations of methyl, ethyl, and benzyl esters were included at the 3- and 5-positions. Affinity was determined in radioligand binding assays at rat brain A(1) and A(2A) receptors using [H-3]-(R)-PIA [[H-3]-(R)-N-6-(phenylisopropyl)adenosine] and [H-3]CGS 21680 [[H-3]-2-[[4-(2-carboxymethyl)phenyl]ethylamino]-5'-(N-ethyl carbamoyl)adenosine], respectively. Affinity was determined at cloned human and rat A(3) receptors using [I-125]AB-MECA [N-6-(4-amino-3-iodobenzyl)-5'-(N-methycarbonyl)adenosine]. Structure-activity analysis indicated that substitution of the phenyl ring of the beta-styryl group but not of the 6-phenyl substituent was tolerated in A(3) receptor selective agents. Replacement of the 6-phenyl ring with a 3-thienyl or 3-furyl group reduced the affinity at A(3) receptors by 4- and g-fold, respectively. A 5-benzyl ester 4-trans-beta-styryl derivative, 26, with a K-i value of 58.3 nM at A(3) receptors, was >1700-fold selective vs either A(1) receptors or A(2A) receptors. Shifting the benzyl ester to the 3-position lowered the affinity at A(3) receptors 3-fold. A 5-benzyl, 3-ethyl ester 4-phenylethynyl derivative, 28, displayed a K-i value of 31.4 nM at A(3) receptors and 1300-fold selectivity vs A(1) receptors. The isomeric 3-benzyl, 5-ethyl diester was >600-fold selective for A(3) receptors. Oxidation of 28 to the corresponding pyridine derivative reduced affinity at A(3) receptors by 88-fold and slightly increased affinity at A(1) receptors.

  DOI：

  10.1021/jm960457c

文献信息

• 6-Phenyl-1,4-dihydropyridine Derivatives as Potent and Selective A₃ Adenosine Receptor Antagonists
  作者：Ji-long Jiang、A. Michiel van Rhee、Neli Melman、Xiao-duo Ji、Kenneth A. Jacobson

  DOI：10.1021/jm960457c

  日期：1996.1.1

  An approach to designing dihydropyridines that bind to adenosine receptors without binding to L-type calcium channels has been described. 1,4-Dihydropyridine derivatives substituted with beta-styryl or phenylethynyl groups at the 4-position and aryl groups at the 6-position were synthesized and found to be selective for human A(3) receptors. Combinations of methyl, ethyl, and benzyl esters were included at the 3- and 5-positions. Affinity was determined in radioligand binding assays at rat brain A(1) and A(2A) receptors using [H-3]-(R)-PIA [[H-3]-(R)-N-6-(phenylisopropyl)adenosine] and [H-3]CGS 21680 [[H-3]-2-[[4-(2-carboxymethyl)phenyl]ethylamino]-5'-(N-ethyl carbamoyl)adenosine], respectively. Affinity was determined at cloned human and rat A(3) receptors using [I-125]AB-MECA [N-6-(4-amino-3-iodobenzyl)-5'-(N-methycarbonyl)adenosine]. Structure-activity analysis indicated that substitution of the phenyl ring of the beta-styryl group but not of the 6-phenyl substituent was tolerated in A(3) receptor selective agents. Replacement of the 6-phenyl ring with a 3-thienyl or 3-furyl group reduced the affinity at A(3) receptors by 4- and g-fold, respectively. A 5-benzyl ester 4-trans-beta-styryl derivative, 26, with a K-i value of 58.3 nM at A(3) receptors, was >1700-fold selective vs either A(1) receptors or A(2A) receptors. Shifting the benzyl ester to the 3-position lowered the affinity at A(3) receptors 3-fold. A 5-benzyl, 3-ethyl ester 4-phenylethynyl derivative, 28, displayed a K-i value of 31.4 nM at A(3) receptors and 1300-fold selectivity vs A(1) receptors. The isomeric 3-benzyl, 5-ethyl diester was >600-fold selective for A(3) receptors. Oxidation of 28 to the corresponding pyridine derivative reduced affinity at A(3) receptors by 88-fold and slightly increased affinity at A(1) receptors.