<6R>-1-(aminocarbonyl)-1,2,3,6-tetrahydro-4-methyl-6-(3-nitrophenyl)-2-oxo-5-pyrimidinecarboxylic acid, 1-methyl ester | 112795-98-9

• 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: <6R>-1-(aminocarbonyl)-1,2,3,6-tetrahydro-4-methyl-6-(3-nitrophenyl)-2-oxo-5-pyrimidinecarboxylic acid, 1-methyl ester
• 英文别名: Isopropyl (4R)-3-aminocarbonyl-6-methyl-4-(3-nitrophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；(R)-SQ 32,926；(R)-SQ 32926；SQ 32926；[6R]-1-(aminocarbonyl)-1,2,3,6-tetrahydro-4-methyl-6-(3-nitrophenyl)-2-oxo-5-pyrimidinecarboxylic acid, 1-methyl ester；propan-2-yl (4R)-3-carbamoyl-6-methyl-4-(3-nitrophenyl)-2-oxo-1,4-dihydropyrimidine-5-carboxylate
• CAS: 112795-98-9
• 化学式: C₁₆H₁₈N₄O₆
• 分子量: 362.342
• InChiKey: JTILQSIVPVPOTG-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  148
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  Isopropyl 3-hydroxymethyl-6-methyl-4-(3-nitrophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate 在 ammonium hydroxide 、 phosphate buffer 、 Thermomyces lanuginosus lipase 、 silica gel 、 三乙胺 、 dextran 作用下， 以 四氢呋喃 、 甲醇 、 异丙醚 为溶剂， 反应 193.0h， 生成 <6R>-1-(aminocarbonyl)-1,2,3,6-tetrahydro-4-methyl-6-(3-nitrophenyl)-2-oxo-5-pyrimidinecarboxylic acid, 1-methyl ester
  参考文献：
  名称：

  Synthesis and reactions of Biginelli-compounds. Part 23. Chemoenzymatic syntheses of enanttiomerically pure 4-aryl-3,4-dihydropyrimidin-2(1H)-ones

  摘要：

  通过脂肪酶催化的酶法拆分两种活化的二氢嘧啶酮酯，制备了对映体纯的二氢嘧啶酮（DHPM）。在第一个模型系列中，通过对不同脂肪酶在两种不同溶剂体系中的分析规模拆分，得到了选择性E < 50的茚满甲酰氧甲基活化的DHPM C5酯10a-c。或者，将乙酰氧甲基残基连接到DHPM骨架的N3位置，产生了活化的酯15，该酯被Thermomyces lanuginosus脂肪酶选择性裂解（E > 200），经脱保护后在中等制备规模上得到DHPM（R）-和（S）-13。处理（R）-13与三氯乙酰异氰酸酯，得到了降压剂（R）-SQ 32926。

  DOI：

  10.1039/b006372j

文献信息

• 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
• Highly Enantioseletive Biginelli Reaction Using a New Chiral Ytterbium Catalyst:  Asymmetric Synthesis of Dihydropyrimidines
  作者：Yijun Huang、Fengyue Yang、Chengjian Zhu

  DOI：10.1021/ja056092f

  日期：2005.11.30

  enantioselective three-component Biginelli condensation catalyzed by a recyclable chiral ytterbium triflate with a novel hexadentate amine phenol ligand containing a pyridyl group has been developed. A wide range of optically active dihydropyrimidines with remarkable pharmacological interest was obtained in high yields with good to excellent enantioselectivities under mild conditions.

  已开发出由可回收的手性三氟甲磺酸镱与含有吡啶基的新型六齿胺苯酚配体催化的高对映选择性三组分 Biginelli 缩合反应。在温和条件下以高产率获得了具有显着药理学意义的多种旋光二氢嘧啶，具有良好到优异的对映选择性。
• Synthesis of enantiomerically pure 4-aryl-3,4-dihydropyrimidin-2(1 H )-ones via enzymatic resolution: preparation of the antihypertensive agent ( R )-SQ 32926 †Synthesis and reactions of Biginelli compounds, part 20; for part 19, see: Kappe, C. O.; Shishkin, O. V.; Uray, G.; Verdino, P. Tetrahedron 2000, 56, 1859–1862. †
  作者：Barbara Schnell、Ulrike T Strauss、Petra Verdino、Kurt Faber、C.Oliver Kappe

  DOI：10.1016/s0957-4166(00)00081-1

  日期：2000.4

  A practical and short synthesis of the enantiomerically pure dihydropyrimidone antitypertensive agent (R)-SQ 32926 has been developed. The key step in the synthesis is the enzymatic resolution of an N3-acetoxymethyl-activated dihdropyrimidone precursor by Thermomyces lanuginosus lipase. The absolute configuration of (R)-SQ 32926 was confirmed by circular dichroism spectroscopy. (C) Elsevier Science Ltd. All rights reserved.
• ATWAL, KARNAIL S.;SWANSON, BRIAN N.;UNGER, STEVEN E.;FLOYD, DAVID M.;MORE+, J. MED. CHEM., 34,(1991) N, C. 806-811
  作者：ATWAL, KARNAIL S.、SWANSON, BRIAN N.、UNGER, STEVEN E.、FLOYD, DAVID M.、MORE+

  DOI：——

  日期：——
• Synthesis and reactions of Biginelli-compounds. Part 23. Chemoenzymatic syntheses of enanttiomerically pure 4-aryl-3,4-dihydropyrimidin-2(1H)-ones
  作者：Barbara Schnell、Wolfram Krenn、Kurt Faber、C. Oliver Kappe

  DOI：10.1039/b006372j

  日期：——

  Enantiomerically pure dihydropyrimidones (DHPMs) were prepared by lipase-catalyzed enzymatic resolution of two types of activated DHPM esters. In the first model series, pivaloyloxymethyl-activated DHPM C5-esters 10a–c were resolved on an analytical scale by various lipases in two different solvent systems with selectivities E < 50. Alternatively, attachment of an acetoxymethyl residue at the N3 position of the DHPM scaffold led to activated ester 15, which was selectively cleaved by Thermomyces lanuginosus lipase (E > 200) to furnish, after deprotection, DHPMs (R)- and (S)-13 on a semi-preparative scale. Treatment of (R)-13 with trichloroacetyl isocyanate produced the antihypertensive agent (R)-SQ 32926.

  通过脂肪酶催化的酶法拆分两种活化的二氢嘧啶酮酯，制备了对映体纯的二氢嘧啶酮（DHPM）。在第一个模型系列中，通过对不同脂肪酶在两种不同溶剂体系中的分析规模拆分，得到了选择性E < 50的茚满甲酰氧甲基活化的DHPM C5酯10a-c。或者，将乙酰氧甲基残基连接到DHPM骨架的N3位置，产生了活化的酯15，该酯被Thermomyces lanuginosus脂肪酶选择性裂解（E > 200），经脱保护后在中等制备规模上得到DHPM（R）-和（S）-13。处理（R）-13与三氯乙酰异氰酸酯，得到了降压剂（R）-SQ 32926。