6-methyl-5-(isopropyloxyarbonyl)-4-(3-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-thione | 301233-27-2

• 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: 6-methyl-5-(isopropyloxyarbonyl)-4-(3-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-thione
• 英文别名: (-)-1,2,3,4-Tetrahydro-6-methyl-4-(3-nitrophenyl)-2-thioxo-5-pyrimidinecarboxylic acid,1-methylethyl ester；Isopropyl 6-methyl-4-(3-nitrophenyl)-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；propan-2-yl 6-methyl-4-(3-nitrophenyl)-2-sulfanylidene-3,4-dihydro-1H-pyrimidine-5-carboxylate
• CAS: 301233-27-2
• 化学式: C₁₅H₁₇N₃O₄S
• 分子量: 335.384
• InChiKey: WPWCZDIAJOUDBH-UHFFFAOYSA-N

物化性质

• 沸点：
  452.5±55.0 °C(Predicted)
• 密度：
  1.35±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  128
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-methyl-5-(isopropyloxyarbonyl)-4-(3-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-thione 、 4-甲氧基氯苄 以 四氢呋喃 为溶剂， 生成 (+)-1,4-dihydro-2-[[(4-methoxyphenyl)methyl]thio]-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid
  参考文献：
  名称：

  1,2,3,4-Tetrahydro-6-substituted-4-aryl(or heterocyclo)-3-((substituted

  摘要：

  心血管活性化合物具有以下通式： ##STR1## 及其药学上可接受的盐，其中X为氧或硫；R为氢、烷基、环烷基、芳基或芳基烷基，R1为氢、烷基、环烷基、芳基、杂环、##STR2##或卤代烷基，或者R和R1与其所连接的氮原子一起形成1-吡咯烷基、1-哌啶基、1-氮杂环庚三烯基、4-吗啉基、4-硫吗啉基、1-哌嗪基、4-烷基-1-哌嗪基、4-芳基烷基-1-哌嗪基、4-二芳基烷基-1-哌嗪基或1-吡咯烷基、1-哌啶基、或1-氮杂环庚三烯基，这些基团可以被烷基、烷氧基、烷硫基、卤素、三氟甲基或羟基取代；R2为氢、烷基、烯基、炔基、环烷基、芳基、##STR3##或卤代烷基；R3为氢、烷基、环烷基、芳基、杂环、##STR4##或卤代烷基；R4为芳基或杂环；R5和R6各自独立为氢、烷基、--(CH2)q--芳基或--(CH2)q--环烷基；Y1为环烷基、芳基、杂环、羟基、烷氧基、芳基--(CH2)m--O--、巯基、烷硫基、芳基--(CH2)m--S--、氨基、取代氨基、氨基甲酰基、##STR5##Y3为羟基、烷氧基、芳基--(CH2)m--O--、巯基、烷硫基、芳基--(CH2)m--S--、##STR6##氨基或取代氨基；q为0、1、2或3；m为0或1至6的整数；n为0或1至5的整数；p为1至5的整数。

  公开号：

  US04855301A1
• 作为产物：
  描述：

  3-O-[(3R,5S)-5-methoxycarbonyl-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-3-yl] 5-O-propan-2-yl 2-[(4-methoxyphenyl)methylsulfanyl]-6-methyl-4-(3-nitrophenyl)-4H-pyrimidine-3,5-dicarboxylate 生成 6-methyl-5-(isopropyloxyarbonyl)-4-(3-nitrophenyl)-3,4-dihydropyrimidin-2(1H)-thione
  参考文献：
  名称：

  ATWAL, KARNAIL;ROVNYAK, GEORGE C.

  摘要：

  DOI：

文献信息

• 2-thio or oxo-4-aryl or heterocyclo-1,5(2H)-pyrimidinedicarboxylic acid
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US05202330A1

  公开（公告）日：1993-04-13

  Pyrimidine compounds of the formula ##STR1## wherein X is sulfur or oxygen, Y is R.sub.11 or --O--R.sub.1, and R.sub.4 is aryl or heterocyclo are disclosed. These compounds are useful as cardiovascular agents, particularly anti-hypertensive agents, due to their calcium entry blocking vasodilator activity.

  公开了符合以下公式的嘧啶化合物##STR1##其中X是硫或氧，Y是R.sub.11或--O--R.sub.1，R.sub.4是芳香族或杂环。这些化合物由于其钙通道阻滞血管扩张剂活性而被用作心血管药物，特别是抗高血压药物。
• Dihydropyrimidine calcium channel blockers: 2-heterosubstituted 4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines
  作者：Karnail S. Atwal、George C. Rovnyak、Joseph Schwartz、Suzanne Moreland、Anders Hedberg、Jack Z. Gougoutas、Mary F. Malley、David M. Floyd

  DOI：10.1021/jm00167a035

  日期：1990.5

  2-Heterosubstituted-4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecar box ylic acid esters 8, which lack the potential CS symmetry of dihydropyridine calcium channel blockers, were prepared and evaluated for biological activity. Biological assays using potassium-depolarized rabbit aorta and radioligand binding techniques showed that some of these compounds are potent mimics of dihydropyridine calcium channel blockers. The combination of a branched ester (e.g. isopropyl, sec-butyl) and an alkylthio group (e.g. SMe) was found to be optimal for biological activity. When compared directly with similarly substituted 2-heteroalkyldihydropyridines 9, dihydropyrimidines 8 were found to be 30-fold less active. The solid-state structure of dihydropyrimidine analogue 8g shows that these compounds can adopt a molecular conformation which is similar to the reported conformation of dihydropyridine calcium channel blockers.
• 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.