3-(Benzyl-methyl-amino)-3-phenyl-propionsaeureethylester | 122059-33-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-(Benzyl-methyl-amino)-3-phenyl-propionsaeureethylester
• 英文别名: Ethyl 3-[benzyl(methyl)amino]-3-phenylpropanoate
• CAS: 122059-33-0
• 化学式: C₁₉H₂₃NO₂
• 分子量: 297.397
• InChiKey: VZVYYPOJPDSYNP-UHFFFAOYSA-N

物化性质

• 沸点：
  390.3±30.0 °C(Predicted)
• 密度：
  1.073±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  22
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-(Benzyl-methyl-amino)-3-phenyl-propionsaeureethylester 在 potassium carbonate 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 作用下， 以 甲醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 20.0h， 生成 {4-[3-(Benzyl-methyl-amino)-3-phenyl-propionyl]-piperazin-1-yl}-(2-methyl-pyridin-3-yl)-acetonitrile
  参考文献：
  名称：

  Synthesis and structure-activity relationships of 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)piperazines as PAF antagonists

  摘要：

  A second generation of (cyanomethyl)piperazines, 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)-piperazines, with increased oral activity was prepared and evaluated in vitro in a PAF-induced platelet aggregation assay (PAG) and in vivo in a PAF-induced hypotension test in normotensive rats (HYP). Oral activity was ascertained through a PAF-induced mortality test in mice (MOR). Attachment of a methyl group at position 2 of our earlier pyridine derivatives resulted in an improvement of 1 order of magnitude or greater in the ID50 of the oral test. Three different types of acyl substituents of similar potency emerge from this work: N-(diphenylmethylamino)acetyl, 3-substituted 3-hydroxy-3-phenylpropionyl, and N-substituted 3-amino-3-phenylpropionyl groups. The most interesting compounds, 26 (UR-12460, PAG IC50 = 0.040 muM, HYP, ID50 = 0.021 mg/kg iv, MOR, ID50 = 0.30 mg/kg po) and 58 (UR- 12519, PAG IC50 = 0.041 muM, HYP, ID50 = 0.015 mg/kg iv, MOR, ID50 = 0.044 mg/kg po), compare favorably with WEB-2086. Compounds 26 and 58 were also tested in active anaphylactic shock (AAS) and endotoxin-induced mortality (EIM) tests. On the basis of these data, compounds 26 and 58 have been selected for further pharmacological development.

  DOI：

  10.1021/jm00072a019
• 作为产物：
  描述：

  苯甲酰乙酸乙酯 在 sodium cyanoborohydride 、 potassium carbonate 作用下， 以 甲醇 、 丁酮 为溶剂， 反应 66.0h， 生成 3-(Benzyl-methyl-amino)-3-phenyl-propionsaeureethylester
  参考文献：
  名称：

  Synthesis and structure-activity relationships of 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)piperazines as PAF antagonists

  摘要：

  A second generation of (cyanomethyl)piperazines, 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)-piperazines, with increased oral activity was prepared and evaluated in vitro in a PAF-induced platelet aggregation assay (PAG) and in vivo in a PAF-induced hypotension test in normotensive rats (HYP). Oral activity was ascertained through a PAF-induced mortality test in mice (MOR). Attachment of a methyl group at position 2 of our earlier pyridine derivatives resulted in an improvement of 1 order of magnitude or greater in the ID50 of the oral test. Three different types of acyl substituents of similar potency emerge from this work: N-(diphenylmethylamino)acetyl, 3-substituted 3-hydroxy-3-phenylpropionyl, and N-substituted 3-amino-3-phenylpropionyl groups. The most interesting compounds, 26 (UR-12460, PAG IC50 = 0.040 muM, HYP, ID50 = 0.021 mg/kg iv, MOR, ID50 = 0.30 mg/kg po) and 58 (UR- 12519, PAG IC50 = 0.041 muM, HYP, ID50 = 0.015 mg/kg iv, MOR, ID50 = 0.044 mg/kg po), compare favorably with WEB-2086. Compounds 26 and 58 were also tested in active anaphylactic shock (AAS) and endotoxin-induced mortality (EIM) tests. On the basis of these data, compounds 26 and 58 have been selected for further pharmacological development.

  DOI：

  10.1021/jm00072a019

文献信息

• A novel oxidative ring-opening reaction of isoxazolidines: syntheses of β-amino ketones and β-amino acid esters from secondary amines
  作者：Shun-Ichi Murahashi、Yoichi Kodera、Tatsuhide Hosomi

  DOI：10.1016/s0040-4039(00)82237-6

  日期：1988.1

  A novel oxidative ring-opening reaction of isoxazolidines upon treatment with an electrophile and subsequently with a basegives β-amino ketones and β-amino acid esters highly efficiently.

  在用亲电试剂处理并随后用碱处理时，异恶唑烷的新的氧化性开环反应非常有效地提供了β-氨基酮和β-氨基酸酯。
• High-Pressure Induced Domino-Horner-Wadsworth-Emmons (HWE) - Michael Reactions
  作者：Senay Has-Becker、Kerstin Bodmann、Reinhard Kreuder、Gabriella Santoni、Tobias Rein、Oliver Reiser

  DOI：10.1055/s-2001-16786

  日期：——

  A new protocol for the alkenylation of carbonyl compounds with phosphonates (Horner-Wadsworth-Emmons reaction) is described. Aldehydes react with phosphonates already at room temperature in the presence of triethylamine without further activation by Lewis-acids if high-pressure (8 kbar) is applied to the system. Based on this protocol a domino process was developed combining the HWE reaction with a Michael reaction, thus allowing the one-pot synthesis of β-amino esters, β-thio esters or β-thio nitriles.

  本文介绍了羰基化合物与膦酸盐发生烯化反应（Horner-Wadsworth-Emmons 反应）的新方案。如果在体系中施加高压（8 kbar），醛与膦酸盐在室温下就能在三乙胺存在下发生反应，而无需路易斯酸进一步活化。在此基础上，我们开发了一种多米诺工艺，将 HWE 反应与迈克尔反应相结合，从而实现了 δ-氨基酯、δ-硫代酯或δ-硫代腈纶的一次合成。
• Synthese von 4-Alkoxy- und 3-nitrosubstituierten Isoxazolidinen durch katalysierte 1,3-dipolare Cycloadditionsreaktionen von Nitronen mit Vinylethern und Nitroolefinen
  作者：Michael Meske

  DOI：10.1002/prac.19973390175

  日期：——

  1,3-Dipolar cycloadditions of the C-phenyl-N-alkylnitrones 1,3 and the C,N-diphenylnitrone (2) with vinyl ethers 5,6 are strongly catalyzed by chiral oxazaborolidines derived from N-arylsulfonyl substituted L-alpha-amino acids valine and tert-butyl leucine and BH3 . THF complex at -22 degrees C to room temperature to give predominantly the 3,5-trans-substituted 5-alkoxy-isoxazolidines 8b - 12b, but with moderate enantioselectivity. Thermal cycloaddition afforded predominantly the 3,5-cis-substituted 5-alkoxy-isoxazolidines 8a - 12a. The cycloaddition of (E)-1-ethyl-2-nitroethene (7) afforded a mixture of cis- and trans-substituted 4-nitro-isoxazolidines 13. The ratio depends on reaction temperature and catalyst. Mild ring cleavage after quarternization of 5-ethoxy-2-methyl-isoxazolidines (8) yields the corresponding beta-amino-esters 27, 28.
• MURAHASHI, SHUN-ICHI;KODERA, YOICHI;HOSOMI, TATSUHIDE, TETRAHEDRON LETT., 29,(1988) N 46, C. 5949-5952
  作者：MURAHASHI, SHUN-ICHI、KODERA, YOICHI、HOSOMI, TATSUHIDE

  DOI：——

  日期：——
• Synthesis and structure-activity relationships of 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)piperazines as PAF antagonists
  作者：Elena Carceller、Manuel Merlos、Marta Giral、Carmen Almansa、Javier Bartroli、Julian Garcia-Rafanell、Javier Forn

  DOI：10.1021/jm00072a019

  日期：1993.10

  A second generation of (cyanomethyl)piperazines, 1-acyl-4-((2-methyl-3-pyridyl)cyanomethyl)-piperazines, with increased oral activity was prepared and evaluated in vitro in a PAF-induced platelet aggregation assay (PAG) and in vivo in a PAF-induced hypotension test in normotensive rats (HYP). Oral activity was ascertained through a PAF-induced mortality test in mice (MOR). Attachment of a methyl group at position 2 of our earlier pyridine derivatives resulted in an improvement of 1 order of magnitude or greater in the ID50 of the oral test. Three different types of acyl substituents of similar potency emerge from this work: N-(diphenylmethylamino)acetyl, 3-substituted 3-hydroxy-3-phenylpropionyl, and N-substituted 3-amino-3-phenylpropionyl groups. The most interesting compounds, 26 (UR-12460, PAG IC50 = 0.040 muM, HYP, ID50 = 0.021 mg/kg iv, MOR, ID50 = 0.30 mg/kg po) and 58 (UR- 12519, PAG IC50 = 0.041 muM, HYP, ID50 = 0.015 mg/kg iv, MOR, ID50 = 0.044 mg/kg po), compare favorably with WEB-2086. Compounds 26 and 58 were also tested in active anaphylactic shock (AAS) and endotoxin-induced mortality (EIM) tests. On the basis of these data, compounds 26 and 58 have been selected for further pharmacological development.