1-methyl 5-isopropyl 4-methyl-6-(3-nitrophenyl)-2-oxo-2,3-dihydropyrimidine-1,5(6H)-dicarboxylate | 1444820-85-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 1-methyl 5-isopropyl 4-methyl-6-(3-nitrophenyl)-2-oxo-2,3-dihydropyrimidine-1,5(6H)-dicarboxylate
• 英文别名: 3-O-methyl 5-O-propan-2-yl 6-methyl-4-(3-nitrophenyl)-2-oxo-1,4-dihydropyrimidine-3,5-dicarboxylate
• CAS: 1444820-85-2
• 化学式: C₁₇H₁₉N₃O₇
• 分子量: 377.354
• InChiKey: KYAYYORCSGKDDP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  27
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  131
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-methyl 5-isopropyl 4-methyl-6-(3-nitrophenyl)-2-oxo-2,3-dihydropyrimidine-1,5(6H)-dicarboxylate 在 Chiralcel OD-H HPLC column (Daicel, 250 x 4.6 mm i.d., 5 mm) 作用下， 以 正己烷 、 异丙醇 为溶剂， 以99%的产率得到
  参考文献：
  名称：

  Antagonism of L-type Ca2+ channels CaV1.3 and CaV1.2 by 1,4-dihydropyrimidines and 4H-pyrans as dihydropyridine mimics

  摘要：

  The L-type calcium channel (LTCC) Ca(v)1.3 is regarded as a new potential therapeutic target for Parkinson's disease. Calcium influx through Ca(v)1.3 LTCC during autonomous pacemaking in adult dopaminergic neurons of the substantia nigra pars compacta is related to the generation of mitochondrial oxidative stress in animal models. Development of a Ca(v)1.3 antagonist selective over Ca(v)1.2 is essential because Ca(v)1.2 pore-forming subunits are the predominant form of LTCCs and are abundant in the central nervous and cardiovascular systems. We have explored 1,4-dihydropyrimidines and 4H-pyrans to identify potent and selective antagonists of Ca(v)1.3 relative to Ca(v)1.2 LTCCs. A library of 36 dihydropyridine (DHP)-mimic 1,4-dihydropyrimidines and 4H-pyrans was synthesized, and promising chiral compounds were resolved. The antagonism studies of Ca(v)1.3 and Ca(v)1.2 LTCCs using DHP mimic compounds showed that dihydropyrimidines and 4H-pyrans are effective antagonists of DHPs for Ca(v)1.3 LTCCs. Some 1,4-dihydropyrimidines are more selective than isradipine for Ca(v)1.3 over Ca(v)1.2, shown here by both calcium flux and patch-clamp electrophysiology experiments, where the ratio of antagonism is around 2-3. These results support the hypothesis that the modified hydrogen bonding donor/acceptors in DHP-mimic dihydropyrimidines and 4H-pyrans can interact differently with DHP binding sites, but, in addition, the data suggest that the binding sites of DHP in Ca(v)1.3 and Ca(v)1.2 LTCCs are very similar. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.054
• 作为产物：
  描述：

  间硝基苯甲醛 在 sodium hydride 、 ytterbium(III) triflate 作用下， 以 四氢呋喃 、 甲苯 、 mineral oil 为溶剂， 反应 5.0h， 生成 1-methyl 5-isopropyl 4-methyl-6-(3-nitrophenyl)-2-oxo-2,3-dihydropyrimidine-1,5(6H)-dicarboxylate
  参考文献：
  名称：

  Antagonism of L-type Ca2+ channels CaV1.3 and CaV1.2 by 1,4-dihydropyrimidines and 4H-pyrans as dihydropyridine mimics

  摘要：

  The L-type calcium channel (LTCC) Ca(v)1.3 is regarded as a new potential therapeutic target for Parkinson's disease. Calcium influx through Ca(v)1.3 LTCC during autonomous pacemaking in adult dopaminergic neurons of the substantia nigra pars compacta is related to the generation of mitochondrial oxidative stress in animal models. Development of a Ca(v)1.3 antagonist selective over Ca(v)1.2 is essential because Ca(v)1.2 pore-forming subunits are the predominant form of LTCCs and are abundant in the central nervous and cardiovascular systems. We have explored 1,4-dihydropyrimidines and 4H-pyrans to identify potent and selective antagonists of Ca(v)1.3 relative to Ca(v)1.2 LTCCs. A library of 36 dihydropyridine (DHP)-mimic 1,4-dihydropyrimidines and 4H-pyrans was synthesized, and promising chiral compounds were resolved. The antagonism studies of Ca(v)1.3 and Ca(v)1.2 LTCCs using DHP mimic compounds showed that dihydropyrimidines and 4H-pyrans are effective antagonists of DHPs for Ca(v)1.3 LTCCs. Some 1,4-dihydropyrimidines are more selective than isradipine for Ca(v)1.3 over Ca(v)1.2, shown here by both calcium flux and patch-clamp electrophysiology experiments, where the ratio of antagonism is around 2-3. These results support the hypothesis that the modified hydrogen bonding donor/acceptors in DHP-mimic dihydropyrimidines and 4H-pyrans can interact differently with DHP binding sites, but, in addition, the data suggest that the binding sites of DHP in Ca(v)1.3 and Ca(v)1.2 LTCCs are very similar. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.04.054

文献信息

• Antagonism of L-type Ca2+ channels CaV1.3 and CaV1.2 by 1,4-dihydropyrimidines and 4H-pyrans as dihydropyridine mimics
  作者：Soosung Kang、Garry Cooper、Sara Fernandez Dunne、Chi-Hao Luan、D. James Surmeier、Richard B. Silverman

  DOI：10.1016/j.bmc.2013.04.054

  日期：2013.7

  The L-type calcium channel (LTCC) Ca(v)1.3 is regarded as a new potential therapeutic target for Parkinson's disease. Calcium influx through Ca(v)1.3 LTCC during autonomous pacemaking in adult dopaminergic neurons of the substantia nigra pars compacta is related to the generation of mitochondrial oxidative stress in animal models. Development of a Ca(v)1.3 antagonist selective over Ca(v)1.2 is essential because Ca(v)1.2 pore-forming subunits are the predominant form of LTCCs and are abundant in the central nervous and cardiovascular systems. We have explored 1,4-dihydropyrimidines and 4H-pyrans to identify potent and selective antagonists of Ca(v)1.3 relative to Ca(v)1.2 LTCCs. A library of 36 dihydropyridine (DHP)-mimic 1,4-dihydropyrimidines and 4H-pyrans was synthesized, and promising chiral compounds were resolved. The antagonism studies of Ca(v)1.3 and Ca(v)1.2 LTCCs using DHP mimic compounds showed that dihydropyrimidines and 4H-pyrans are effective antagonists of DHPs for Ca(v)1.3 LTCCs. Some 1,4-dihydropyrimidines are more selective than isradipine for Ca(v)1.3 over Ca(v)1.2, shown here by both calcium flux and patch-clamp electrophysiology experiments, where the ratio of antagonism is around 2-3. These results support the hypothesis that the modified hydrogen bonding donor/acceptors in DHP-mimic dihydropyrimidines and 4H-pyrans can interact differently with DHP binding sites, but, in addition, the data suggest that the binding sites of DHP in Ca(v)1.3 and Ca(v)1.2 LTCCs are very similar. (C) 2013 Elsevier Ltd. All rights reserved.