2-(1-oxo-butyl)-glutaric acid diethyl ester | 858795-64-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 英文名称: 2-(1-oxo-butyl)-glutaric acid diethyl ester
• 英文别名: 2-(1-Oxo-butyl)-glutarsaeure-diaethylester；diethyl 2-butanoylpentanedioate
• CAS: 858795-64-9
• 化学式: C₁₃H₂₂O₅
• 分子量: 258.315
• InChiKey: QBVCWEQTQBTFNK-UHFFFAOYSA-N

物化性质

• 沸点：
  161-163 °C(Press: 10.5 Torr)
• 密度：
  1.043±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.88
• 重原子数：
  18.0
• 可旋转键数：
  9.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  69.67
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  2-(1-oxo-butyl)-glutaric acid diethyl ester 在 sodium ethanolate 、 N,N-二甲基苯胺 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 24.0h， 生成 3-(4-氯-2-甲基-6-丙基-嘧啶-5-基)-丙酸乙酯
  参考文献：
  名称：

  Pyrido[2,3-d]pyrimidine Angiotensin II Antagonists

  摘要：

  A series of pyrido[2,3-d]pyrimidine angiotensin II (A II) antagonists was synthesized and tested for antagonism of A II. Compounds with a biphenylyltetrazole pharmacophore and small alkyl groups at the 2- and ii-positions Of the pyridopyrimidine ring were found to be the most potent in an AT(1) receptor binding assay and in blocking the A II presser response in anesthetized, ganglion-blocked A II-infused rats. 5,8-Dihydro-2,4-dimethyl-8-[(2'-(1H-tetrazol-5-yl)[1,1'-biphenyl]-4-yl)methyl] pyrido[2,3-d]pyrimidin-7(6H)-one (4a) was one of the more potent compounds in the binding assay and was the most efficacious compound in the A II-infused rat model. Further study of 4a;in Goldblatt (2K-1C) rats showed the compound to have oral bioavailability and to be an efficacious and potent compound in a high renin form of hypertension.

  DOI：

  10.1021/jm00030a013
• 作为产物：
  描述：

  3-碘丙酸乙酯 、 丁酰乙酸乙酯 在 sodium ethanolate 作用下， 生成 2-(1-oxo-butyl)-glutaric acid diethyl ester
  参考文献：
  名称：

  Franke; Kroupa, Monatshefte fur Chemie, 1936, vol. 69, p. 190

  摘要：

  DOI：

文献信息

• Synthesis and antihypertensive activity of pyrimidin-4(3H)-one derivatives as losartan analogue for new angiotensin II receptor type 1 (AT1) antagonists
  作者：Tae Woo Kim、Byoung Wook Yoo、Joon Kwang Lee、Ji Han Kim、Kyung-Tae Lee、Yong Ha Chi、Jae Yeol Lee

  DOI：10.1016/j.bmcl.2011.12.116

  日期：2012.2

  The discovery, in vitro and in vivo studies of the highly potent AT1 antagonist 12a (BR-A-657, Fimasartan) antagonists are presented. A series of pyrimidin-4(3H)-one derivatives as losartan analogue were synthesized and evaluated for a novel class of AT1 receptor antagonists. Among them, 12a containing thioamido moiety displayed both high in vitro functional antagonism and binding affinity [IC50 = 0

  提出了高效AT 1拮抗剂12a（BR-A-657，Fimasartan）拮抗剂的发现，体内和体外研究。合成了一系列作为氯沙坦类似物的嘧啶4-4（3 H）-one衍生物，并对其进行了一类新型的AT 1受体拮抗剂的评价。其中，含有硫酰胺基部分的12a表现出较高的体外功能拮抗作用和结合亲和力[分别为IC 50  = 0.42和0.13 nM]，并在具有ED 50的成髓大鼠中强烈抑制了AngII诱导的升压反应。0.018 mg / kg。此外，在速尿治疗的大鼠和清醒的肾性高血压大鼠模型中进行的体内评估以及药代动力学研究表明，12a是一种高效且口服活性的AT 1选择性拮抗剂，具有比氯沙坦更强的体内效力。
• Differential effects of UTP and ATP on ion transport in porcine tracheal epithelium
  作者：S K Inglis、R E Olver、S M Wilson

  DOI：10.1038/sj.bjp.0703324

  日期：2000.5

  Isolated segments of porcine tracheal epithelium were mounted in Ussing chambers, current required to maintain transepithelial potential difference at 0 mV (short circuit current, ISC) was monitored and effects of nucleotides upon ISC were studied. Mucosal UTP (100 μM) evoked a transient rise in ISC that was followed by a sustained fall below basal ISC maintained for 30 min. Mucosal ATP (100 μM) also stimulated a transient rise in ISC but in contrast to UTP did not inhibit basal ISC. Submucosal UTP and ATP both transiently increased ISC. UTP‐prestimulated epithelia were refractory to ATP but prestimulation with ATP did not abolish the response to UTP. The epithelia thus appear to express two populations of apical receptors allowing nucleotides to modulate ISC. The UTP‐induced rise was reduced by pretreatment with either bumetanide (100 μM), diphenylamin‐2‐carboxylic acid (DPC, 1 mM), or Cl− and HCO3−‐free solution whilst the fall was abolished by amiloride pretreatment. Thapsigargin (0.3 μM) abolished the UTP‐induced increase in ISC but not the subsequent decrease. Staurosporine (0.1 μM) inhibited basal ISC and blocked UTP‐induced inhibition of ISC. Inhibitors of either protein kinase C (PKC) (D‐erythro sphingosine) or PKA (H89) had no effect. This study suggests that UTP stimulates Cl− secretion and inhibits basal Na+ absorption. ATP has a similar stimulatory effect, which may be mediated by activation of P2Y2 receptors and an increase in [Ca2+]in, but no inhibitory effect, which is likely mediated by activation of a pyrimidine receptor and possible inhibition of a protein kinase other than PKC or PKA. British Journal of Pharmacology (2000) 130, 367–374; doi:10.1038/sj.bjp.0703324

  以下是文本的中文翻译： 将猪气管上皮的分离段放置于尤金箱（Ussing chamber）中，监测维持跨上皮电位差为0 mV所需的电流（短路电流，ISC），并研究核苷酸对ISC的影响。 黏膜侧的UTP（100 μM）引发短暂的ISC上升，随后出现持续30分钟的基线ISC下降。黏膜侧的ATP（100 μM）同样刺激短暂的ISC上升，但与UTP不同，它并未抑制基线ISC。而基底侧的UTP和ATP均短暂增加ISC。 预刺激UTP的上皮对ATP无反应，但以ATP预刺激并不会消除对UTP的反应。这些结果表明，上皮细胞表面存在两组受体，使核苷酸能够调节ISC。 UTP诱导的上升被预先用布美他尼（100 μM）、二苯基氨基-2-羧酸（DPC，1 mM）或无Cl−和HCO3−的溶液处理所抑制，而下降则被预先用阿米洛利处理所消除。 Thapsigargin（0.3 μM）消除了UTP诱导的ISC增加，但未影响随后的下降。Staurosporine（0.1 μM）抑制基线ISC并阻断UTP诱导的ISC抑制。蛋白激酶C（PKC）抑制剂（D-赤藓醇基鞘氨醇）或蛋白激酶A（PKA）抑制剂（H89）均无作用。 本研究表明，UTP刺激Cl−分泌并抑制基线Na+吸收。ATP具有类似的刺激作用，可能是通过激活P2Y2受体和增加[Ca2+]in介导，但无抑制作用，这可能是通过激活嘧啶受体并可能抑制其他蛋白激酶（而非PKC或PKA）。 《英国药理学杂志》 (2000), 130, 367–374; doi:10.1038/sj.bjp.0703324