2,4,6-Trimethyl-3-ethoxycarbonyl-5-methoxycarbonyl-1,4-dihydropyridine | 53632-38-5

• 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: 2,4,6-Trimethyl-3-ethoxycarbonyl-5-methoxycarbonyl-1,4-dihydropyridine
• 英文别名: 5-O-ethyl 3-O-methyl 2,4,6-trimethyl-1,4-dihydropyridine-3,5-dicarboxylate
• CAS: 53632-38-5
• 化学式: C₁₃H₁₉NO₄
• 分子量: 253.298
• InChiKey: NPBBKPIIJDDDBI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2,4,6-Trimethyl-3-ethoxycarbonyl-5-methoxycarbonyl-1,4-dihydropyridine 在 四氯苯醌 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以57.9%的产率得到2,4,6-Trimethyl-pyridine-3,5-dicarboxylic acid 3-ethyl ester 5-methyl ester
  参考文献：
  名称：

  Interaction of 1,4-Dihydropyridine and Pyridine Derivatives with Adenosine Receptors:  Selectivity for A₃ Receptors

  摘要：

  1,4-Dihydropyridine and pyridine derivatives bound to three subtypes of adenosine receptors in the micromolar range. 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-carboxyethyl)phenyl]ethylamino]-5'-(N-ethylcarbamoyl)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-methylcarbamoyl)adenosine]. Structure-activity analysis at adenosine receptors indicated that sterically bulky groups at the 4-, 5-, and 6-positions are tolerated. (R,S)-Nicardipine, 12, displayed K-i values of 19.6 and 63.8 mu M at rat A(1) and A(2A) receptors, respectively, and 3.25 mu M at human A(3) receptors. Similarly, (R)-niguldipine, 14, displayed K-i values of 41.3 and 1.90 mu M at A(1) and A(3) receptors, respectively, and was inactive at A(2A) receptors. A preference for the R- vs the S-enantiomer was observed for several dihydropyridines at adenosine receptors, in contrast with the selectivity at L-type Ca2+ channels. A 4-trans-beta-styryl derivative, 24, with a K-i value of 0.670 mu M at A(3) receptors, was 24-fold selective vs A(1) receptors (K-i = 16.1 mu M) and 74-fold vs A(2A) receptors (K-i = 49.3 mu M). The affinity of 24 at L-type Ca2+ channels, measured in rat brain membranes using [H-3]isradipine, indicated a K-i value of 0.694 mu M, and the compound is thus nonselective between A(3) receptors and L-type Ca2+ channels. Inclusion of a 6-phenyl group enhanced A(3) receptor selectivity: Compound 28 (MRS1097; 3,5-diethyl 2-methyl-6-phenyl-4-(trans-2-phenylvinyl)-1,4(R,S)-dihydro-pyridine-3,5-dicarboxylate) was 55-fold selective vs A(1) receptors, 44-fold selective vs A(2A) receptors, and over 1000-fold selective vs L-type Ca2+ channels. In addition, compound 28 attenuated the A(3) agonist-elicited inhibitory effect on adenylylcyclase. Furthermore, whereas nicardipine, 12, displaced radioligand from the Na+-independent adenosine transporter with an apparent affinity of 5.36 +/- 1.51 mu M, compound 28 displaced less than 10% of total binding at a concentration of 100 mu M. Pyridine derivatives, when bearing a 4-alkyl but not a 4-phenyl group, maintained affinity for adenosine receptors. These findings indicate that the dihydropyridines may provide leads for the development of novel, selective A(3) adenosine antagonists.

  DOI：

  10.1021/jm9600205
• 作为产物：
  描述：

  3-ethoxycarbonyl-3-penten-2-one 在 氢氧化钾 作用下， 以 1,4-二氧六环 为溶剂， 反应 22.0h， 生成 2,4,6-Trimethyl-3-ethoxycarbonyl-5-methoxycarbonyl-1,4-dihydropyridine
  参考文献：
  名称：

  Esters of 1,4-dihydropyridine-3- and -3,5-carbothiolic acids

  摘要：

  DOI：

  10.1007/bf00512963

文献信息

• 1,4-Dihydropyridines, processes for their preparation and their use as antithrombotic drugs
  申请人：ALTER, S.A.

  公开号：EP0253092B1

  公开（公告）日：1991-09-25
• VIGANTE, B. A.;OZOLS, YA. YA.;DUBUR, G. YA.;BEJLIS, YU. I.;BELASH, E. M.;+, XIMIYA GETEROTSIKL. SOEDIN., 1982, N 2, 219-228
  作者：VIGANTE, B. A.、OZOLS, YA. YA.、DUBUR, G. YA.、BEJLIS, YU. I.、BELASH, E. M.、+

  DOI：——

  日期：——
• US4782069A
  申请人：——

  公开号：US4782069A

  公开（公告）日：1988-11-01