1,4-二氢-2-甲氧基-6-甲基-4-(3-硝基苯基)-5-嘧啶羧酸乙酯 | 106720-60-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 1,4-二氢-2-甲氧基-6-甲基-4-(3-硝基苯基)-5-嘧啶羧酸乙酯
• 英文名称: 1,4-dihydro-2-methoxy-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid ethyl ester
• 英文别名: 1,4-Dihydro-2-methoxy-6-methyl-4-(3-nitrophenyl)-5-pyrimidinecarboxylic acid, ethyl ester；ethyl 2-methoxy-6-methyl-4-(3-nitrophenyl)-1,4-dihydropyrimidine-5-carboxylate
• CAS: 106720-60-9
• 化学式: C₁₅H₁₇N₃O₅
• 分子量: 319.317
• InChiKey: RVBQIBMRQBVLMH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  106
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,4-二氢-2-甲氧基-6-甲基-4-(3-硝基苯基)-5-嘧啶羧酸乙酯 在 吡啶 、 三氟乙酸 、 乙硫醇 、 柠檬酸 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 生成 3,6-dihydro-4-methyl-6-(3-nitrophenyl)-2-thioxo-1,5(2H)-pyrimidinedicarboxylic acid bis(ethyl ester)
  参考文献：
  名称：

  Substituted 1,4-dihydropyrimidines. 3. Synthesis of selectively functionalized 2-hetero-1,4-dihydropyrimidines

  摘要：

  DOI：

  10.1021/jo00286a020
• 作为产物：
  描述：

  ethyl (Z)-2-(3-nitrobenzylidene)-3-oxobutanoate 、 O-甲基异脲 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以72%的产率得到1,4-二氢-2-甲氧基-6-甲基-4-(3-硝基苯基)-5-嘧啶羧酸乙酯
  参考文献：
  名称：

  Dihydropyrimidine calcium channel blockers: 2-heterosubstituted 4-aryl-1,4-dihydro-6-methyl-5-pyrimidinecarboxylic acid esters as potent mimics of dihydropyridines

  摘要：

  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.

  DOI：

  10.1021/jm00167a035

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。
• 1,2,3,4-Tetrahydro-6-substituted-4-aryl(or heterocyclo)-3-((substituted
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04855301A1

  公开（公告）日：1989-08-08

  Cardiovascular activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof wherein X is oxygen or sulfur; R is hydrogen, alkyl, cycloalkyl, aryl, or arylalkyl and R.sub.1 is hydrogen, alkyl, cycloalkyl, aryl, heterocyclo, ##STR2## or halo substituted alkyl, or R and R.sub.1 taken together with the nitrogen atom to which they are attached are 1-pyrrolidinyl, 1-piperidinyl, 1-azepinyl, 4-morpholinyl, 4-thiamorpholinyl, 1-piperazinyl, 4-alkyl-1-piperazinyl, 4-arylalkyl-1-piperazinyl, 4-diarylalkyl-1-piperazinyl or 1-pyrrolidinyl, 1-piperidinyl, or 1-azeipinyl substituted with alkyl, alkoxy, alkylthio, halo, trifluoromethyl or hydroxy; R.sub.2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, ##STR3## or halo substituted alkyl; R.sub.3 is hydrogen, alkyl, cycloalkyl, aryl, heterocyclo, ##STR4## or halo substituted alkyl; R.sub.4 is aryl or heterocyclo; R.sub.5 and R.sub.6 are each independently hydrogen, alkyl, --(CH.sub.2).sub.q --aryl or --(CH.sub.2).sub.q --cycloalkyl; Y.sub.1 is cycloalkyl, aryl, heterocyclo, hydroxyl, alkoxy, aryl--(CH.sub.2).sub.m --O--, mercapto, alkylthio, aryl--(CH.sub.2).sub.m --S--, amino, substituted amino, carbamoyl, ##STR5## Y.sub.3 is hydroxyl, alkoxy, aryl--(CH.sub.2).sub.m --O--, mercapto, alkylthio, aryl--(CH.sub.2).sub.m --S--, ##STR6## amino, or substituted amino; q is 0, 1, 2 or 3; m is 0 or an integer of 1 to 6; n is 0 or an integer of 1 to 5; and p is an integer of 1 to 5.

  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。
• 2-substituted thio or oxy-4-aryl or
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04728652A1

  公开（公告）日：1988-03-01

  1,4-Dihydropyrimidines of the formula ##STR1## wherein X is sulfur or oxygen and R.sub.4 is aryl or heterocyclo and disclosed. These compounds are useful as cardiovacular agents, particularly anti-hypertensive agents, due to their vasodilator activity.

  该公式为##STR1##的1,4-二氢嘧啶化合物，其中X为硫或氧，R.sub.4为芳基或杂环基。这些化合物可用作心血管药物，特别是抗高血压药物，因为它们具有扩血管活性。
• Dihydropyrimidine calcium channel blockers. 3. 3-Carbamoyl-4-aryl-1,2,3,4-tetrahydro-6-methyl-5-pyrimidinecarboxylic acid esters as orally effective antihypertensive agents
  作者：Karnail S. Atwal、Brian N. Swanson、Steven E. Unger、David M. Floyd、Suzanne Moreland、Anders Hedberg、Brian C. O'Reilly

  DOI：10.1021/jm00106a048

  日期：1991.2

  18 by treatment with (R)-alpha-methylbenzylamine. Our results demonstrate that the active R-(-)-enantiomer 20a of 7 is both more potent and longer acting than nifedipine (1) as an antihypertensive agent in the SHR. The in vivo potency and duration of 20a is comparable to the long-acting dihydropyridine amlodipine. The superior oral antihypertensive activity of 20a compared to that of previously described

  为了解释中等活性（IC50 = 3.2 microM）二氢嘧啶钙通道阻滞剂5的有效降压活性，我们在大鼠中进行了药物代谢研究，发现5被代谢为化合物6-10。已发现其中两种代谢物6（IC50 = 16 nM）和7（IC50 = 12 nM）负责化合物5的降压活性。体内6到7的潜在代谢使我们对研究与以下物质有关的化合物的兴趣减弱了6.结构活性研究旨在鉴定其他7的芳基取代的类似物，在体内具有可比的潜力，导致17g，j，p，尽管这些化合物在体外的效力不及7。为了研究绝对立体化学对效能的影响，我们通过由（R）-α-甲基苄基胺处理从18制备的非对映异构脲19a，b拆分了7。我们的结果表明，与硝苯地平（1）作为SHR中的降压药相比，活性7的活性R-（-）-对映体20a既有效，又作用更长。20a的体内效力和持续时间与长效二氢吡啶氨氯地平相当。与先前描述的氨基甲酸酯2（R2 = COOEt）相比，20a的口服
• 2-(substituted
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04689414A1

  公开（公告）日：1987-08-25

  Cardiovascular activity is exhibited by compounds having the formula ##STR1## and pharmaceutically acceptable salts thereof, wherein R.sub.1 is alkyl, cycloalkyl, aryl, heterocyclo, --(CH.sub.2).sub.n --Y.sub.2, --(CH.sub.2).sub.p --Y.sub.3 or halo substituted alkyl; R.sub.2 is hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, aryl, --(CH.sub.2).sub.n --Y.sub.1, or halo substituted alkyl; R.sub.3 is hydrogen, alkyl, cycloalkyl, aryl, heterocyclo, --(CH.sub.2).sub.n --Y.sub.2, --(CH.sub.2).sub.p --Y.sub.3, or halo substituted alkyl; R.sub.4 is aryl or heterocyclo; R.sub.5 is hydrogen, alkyl, aryl, arylalkyl, cyano, nitro, ##STR2## Y.sub.1 is cycloalkyl, aryl, heterocyclo, hydroxyl, alkoxy, aryl-(CH.sub.2).sub.m --O--, mercapto, alkylthio, aryl-(CH.sub.2).sub.m --S--, amino, substituted amino, carbamoyl, ##STR3## Y.sub.2 is cycloalkyl, aryl, heterocyclo, carbamoyl, ##STR4## amino, or substituted amino; m is 0 or an integer of 1 to 6; n is an integer of 1 to 6; and p is an integer of 2 to 6.

  具有以下式子及其药学上可接受的盐的化合物表现出心血管活性：##STR1## 其中，R.sub.1是烷基、环烷基、芳基、杂环烷基、--(CH.sub.2).sub.n --Y.sub.2、--(CH.sub.2).sub.p --Y.sub.3或卤代烷基；R.sub.2是氢、烷基、烯基、炔基、环烷基、芳基、--(CH.sub.2).sub.n --Y.sub.1或卤代烷基；R.sub.3是氢、烷基、环烷基、芳基、杂环烷基、--(CH.sub.2).sub.n --Y.sub.2、--(CH.sub.2).sub.p --Y.sub.3或卤代烷基；R.sub.4是芳基或杂环烷基；R.sub.5是氢、烷基、芳基、芳基烷基、氰基、硝基、##STR2## Y.sub.1是环烷基、芳基、杂环烷基、羟基、烷氧基、芳基-(CH.sub.2).sub.m --O--、巯基、烷硫基、芳基-(CH.sub.2).sub.m --S--、氨基、取代氨基、氨基甲酰基、##STR3## Y.sub.2是环烷基、芳基、杂环烷基、氨基甲酰基、##STR4## 氨基或取代氨基；m为0或1到6的整数；n为1到6的整数；p为2到6的整数。