<6S>-1-(aminocarbonyl)-1,2,3,6-tetrahydro-4-methyl-6-(3-nitrophenyl)-2-oxo-5-pyrimidinecarboxylic acid, 1-methylethyl ester | 112795-97-8

• 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: <6S>-1-(aminocarbonyl)-1,2,3,6-tetrahydro-4-methyl-6-(3-nitrophenyl)-2-oxo-5-pyrimidinecarboxylic acid, 1-methylethyl ester
• 英文别名: Isopropyl (4S)-3-aminocarbonyl-6-methyl-4-(3-nitrophenyl)-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate；(S)-SQ 32926；[6S]-1-(aminocarbonyl)-1,2,3,6-tetrahydro-4-methyl-6-(3-nitrophenyl)-2-oxo-5-pyrimidinecarboxylic acid, 1-methylethyl ester；propan-2-yl (4S)-3-carbamoyl-6-methyl-4-(3-nitrophenyl)-2-oxo-1,4-dihydropyrimidine-5-carboxylate
• CAS: 112795-97-8
• 化学式: C₁₆H₁₈N₄O₆
• 分子量: 362.342
• InChiKey: JTILQSIVPVPOTG-ZDUSSCGKSA-N

物化性质

• 熔点：
  160-161 °C
• 密度：
  1.368±0.06 g/cm3(Predicted)

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 <6S>-1-(aminocarbonyl)-1,2,3,6-tetrahydro-4-methyl-6-(3-nitrophenyl)-2-oxo-5-pyrimidinecarboxylic acid, 1-methylethyl 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
• 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。