2-tert-Butyl-4-methylsulfanyl-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile | 96823-94-8

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 2-tert-Butyl-4-methylsulfanyl-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile
• 英文别名: 2-tert-butyl-4-methylsulfanyl-6-oxo-1H-pyrimidine-5-carbonitrile
• CAS: 96823-94-8
• 化学式: C₁₀H₁₃N₃OS
• 分子量: 223.299
• InChiKey: LCEBODHLVPEMPK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  90.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-tert-Butyl-4-methylsulfanyl-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile 在 sodium hydroxide 、 硫酸 、 sodium hydride 作用下， 以 1,4-二氧六环 为溶剂， 反应 23.25h， 生成 (2-tert-Butyl-5-carbamoyl-6-methylsulfanyl-pyrimidin-4-yloxy)-acetic acid
  参考文献：
  名称：

  (Pyrimidinyloxy)acetic acids and pyrimidineacetic acids as a novel class of aldose reductase inhibitors

  摘要：

  Pyrimidineacetic acids and (pyrimidinyloxy)acetic acids were synthesized by alkylation, with methyl bromoacetate or tert-butyl bromoacetate as alkylating agents. Alkylation reaction at the nitrogen or oxygen atom for different substrates was found to be solvent dependent. N-Alkylation was favored in ethereal solvent, e.g., tetrahydrofuran and dimethoxyethane, whereas O-alkylation was predominant in dimethylformamide. These compounds were tested in vitro to determine their ability to inhibit bovine lens aldose reductase. Selected compounds were assayed in vivo, in a 4-day galactose-fed rat model. The decrease in galactitol from the control was determined in lens, nerve, and diaphragm. Several of the 6-oxopyrimidine-1-acetic acids and (pyrimidinyl-4-oxy)acetic acids were found to be potent inhibitors of bovine lens aldose reductase. A study was also undertaken to determine in vitro the transport behavior of selected compounds in the isolated rat sciatic nerve. A discussion of the structure-activity relationship of this class of compounds with reference to their intrinsic biochemical activity is reported. It is concluded, in general, that ability of a compound to penetrate the tissue membrane plays an important role in the genesis of in vivo lens aldose reductase (LAR) inhibitory activity.

  DOI：

  10.1021/jm00172a034
• 作为产物：
  描述：

  2,2-二甲基丙亚胺盐酸 、 2-氰-3,3-二(甲硫基)丙烯酸甲酯 生成 2-tert-Butyl-4-methylsulfanyl-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile
  参考文献：
  名称：

  BAGLI, JEHAN;BOGRI, T.;PALAMETA, B.;RAKHIT, S.;PESECKIS, S.;MCQUILLAN, J.+, J. MED. CHEM., 31,(1988) N 4, 814-823

  摘要：

  DOI：

文献信息

• Amino-pyrimidine derivatives
  申请人：AMERICAN HOME PRODUCTS CORPORATION

  公开号：EP0130735A1

  公开（公告）日：1985-01-09

  The invention concerns compounds of the formula I in which R' is lower alkyl, cyclo(lower)alkyl, phenyl(lower)alkyl, or trifluoromethyl; R2 is oxo, thioxo or imino; R3 is cyano, aminocarbonyl, nitro, methylsulfonyl or aminosulfonyl; R4, R5, R6, R7 and R8 each independently is hydrogen or lower alkyl; R9 is hydrogen, lower alkenyl, 1-piperidinyl, 1-pyrrolidinyl, 1-piperazinyl, lower alkynyl, cyclo(lower)alkyl, 2, 3 or 4-pyridinyl, 2 or 3-furanyl, 2 or 3-indolyl, 2 or 3-thienyl, 5-imidazolyl, 4-morpholinyl, phenyl, phenyl mono- or disubstituted with hydroxy or lower alkoxy, 4-thiomorpholinyl, pyrazinyl, pyridazinyl, triazinyl, pyrrolyl, pyrazolyl, thiazolyl, oxadiazolyl, thiadiazolyl, isoxazolyl, furazolyl, oxathiazolyl, quinolinyl, isoquinolinyl, pyridopyrimidinyl, benzoxazolyl, benzimidazolyl, benzthiazolyl, benzoxazinyl, benzpyronyl, isoindolyl, or indolazinyl; and m and n each independently is an integer 0 to 2; or a therapeutically acceptable addition salt thereof for use in increasing cardiac contractility in mammals. Processes for their preparation and pharmaceutical compositions containing them also disclosed.

  本发明涉及式 I 的化合物 其中，R'为低级烷基、环（低级）烷基、苯基（低级）烷基或三氟甲基；R2为氧代、硫代或亚氨基；R3为氰基、氨基羰基、硝基、甲磺酰基或氨基磺酰基；R4、R5、R6、R7和R8各自独立地为氢或低级烷基；R9 是氢、低级烯基、1-哌啶基、1-吡咯烷基、1-哌嗪基、低级炔基、环（低级）烷基、2、3 或 4-吡啶基、2 或 3-呋喃基、2 或 3-吲哚基、2 或 3-噻吩基、5-咪唑基、4-吗啉基、苯基、与羟基或低级烷氧基单取代或二取代的苯基、4-硫代吗啉基、吡嗪基、哒嗪基、三嗪基、吡咯基、吡唑基、噻唑基、噁二唑基、噻二唑基、异噁唑基、呋喃唑基、噁硫唑基、喹啉基、异喹啉基、吡啶嘧啶基、苯并噁唑基、苯并咪唑基、苯并噻唑基、苯并噁嗪基、苯并吡喃基、异吲哚基或吲哚嗪基；m和n各自独立地为0至2的整数；或其治疗上可接受的添加盐，用于增加哺乳动物的心脏收缩力。还公开了其制备方法和含有它们的药物组合物。
• Chemistry and positive inotropic effect of pelrinone and related derivatives. A novel class of 2-methylpyrimidones as inotropic agents
  作者：Jehan Bagli、T. Bogri、B. Palameta、S. Rakhit、S. Peseckis、J. McQuillan、D. K. H. Lee

  DOI：10.1021/jm00399a023

  日期：1988.4

  A novel series of pyrimidine derivatives was synthesized and evaluated for positive inotropic activity. Inotropic and chronotropic effects were determined in vitro in cat papillary muscle and right atrium, respectively. Selected compounds were then evaluated in vivo in a dog heart failure model. Changes in ventricular dP/dt, heart rate, and blood pressure were monitored. Several of these agents produced relatively minor changes in heart rate. This class of agents demonstrated a varying degree of vasodilator effects concomitant with increases in ventricular contractility. The most potent analogues, 9, 48, and 49, were evaluated orally in conscious dogs with implanted Konisberg pressure transducers, and their effect on left ventricular dP/dt was compared with that of milrinone. Mechanistically, the agents of this novel class appear not to mediate their effect via beta-receptors or inhibition of Na+/K+-ATPase. A major component of their inotropic effect is mediated by the inhibition of cardiac phosphodiesterase (PDE)-Fr. III. This was clearly demonstrated by 9, 48, and 49. Compound 48 was found to be the most potent inhibitor of PDE-Fr. III from among the compounds tested in this assay.
• ELLINGBOE, JOHN;ALESSI, THOMAS;MILLEN, JANE;SREDY, JANET;KING, ANDREW;PRU+, J. MED. CHEM., 3,(1990) N0, C. 2892-2899
  作者：ELLINGBOE, JOHN、ALESSI, THOMAS、MILLEN, JANE、SREDY, JANET、KING, ANDREW、PRU+

  DOI：——

  日期：——
• BAGLI, JEHAN;BOGRI, T.;PALAMETA, B.;RAKHIT, S.;PESECKIS, S.;MCQUILLAN, J.+, J. MED. CHEM., 31,(1988) N 4, 814-823
  作者：BAGLI, JEHAN、BOGRI, T.、PALAMETA, B.、RAKHIT, S.、PESECKIS, S.、MCQUILLAN, J.+

  DOI：——

  日期：——
• US4505910A
  申请人：——

  公开号：US4505910A

  公开（公告）日：1985-03-19