aza-phenylalaninylproline tert-butyl ester | 1329063-51-5

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: aza-phenylalaninylproline tert-butyl ester
• 英文别名: tert-butyl (2S)-1-[amino(benzyl)carbamoyl]pyrrolidine-2-carboxylate;hydrochloride
• CAS: 1329063-51-5
• 化学式: C₁₇H₂₅N₃O₃*ClH
• 分子量: 355.865
• InChiKey: KNLDEWFFQCKGJT-UQKRIMTDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.71
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  75.9
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  aza-phenylalaninylproline tert-butyl ester 在 N-甲基吗啉 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium hydroxide 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 0.25h， 生成 phenylacetyl-aza-phenylalaninyl-(2S)-prolyl-(2S)-(3-pyridyl)-alaninyl-(3S)-β-homophenylalanine
  参考文献：
  名称：

  Targeting the Prostaglandin F2α Receptor for Preventing Preterm Labor with Azapeptide Tocolytics

  摘要：

  The prostaglandin-F2 alpha (PGF2 alpha) receptor (FP) was targeted to develop tocolytic agents for inhibiting preterm labor. Azabicycloalkane and azapeptide mimics 2-10 were synthesized based on the (3S,6S,9S)-indolizidin-2-one amino acid analogue PDC113.824 (1), which was shown to modulate FP by a biased allosteric mechanism, involving both G alpha q- and G alpha 12-mediated signaling pathways, and exhibited significant tocolytic activity delaying preterm labor in a mouse model (Goupil; J. Biol. Chem. 2010, 285,25624-25636), Although changes in azabicycloalkane stereochemistry and ring size caused loss of activity, replacement of the indolizidin-2-one amino acid with azaGly-Pro and azaPhe-Pro gave azapeptides 6 and 8, which reduced PGF2 alpha-induced myometrial contractions, potentiated the effect of PGF2 alpha on G alpha q-mediated ERK1/2 activation, and inhibited FP modulation of cell ruffling, a response dependent on the G alpha 12/RhoA/ROCK signaling pathway. Revealing complementarities of azabicycloalkane and azapeptide mimics, novel probes, and efficient tocolytic agents were made to study allosteric modulation of the FP receptor.

  DOI：

  10.1021/jm200608k
• 作为产物：
  描述：

  benzhydrylidene aza-phenylalaninyl-proline tert-butyl ester 在 吡啶 、 盐酸羟胺 作用下， 以88%的产率得到aza-phenylalaninylproline tert-butyl ester
  参考文献：
  名称：

  Targeting the Prostaglandin F2α Receptor for Preventing Preterm Labor with Azapeptide Tocolytics

  摘要：

  The prostaglandin-F2 alpha (PGF2 alpha) receptor (FP) was targeted to develop tocolytic agents for inhibiting preterm labor. Azabicycloalkane and azapeptide mimics 2-10 were synthesized based on the (3S,6S,9S)-indolizidin-2-one amino acid analogue PDC113.824 (1), which was shown to modulate FP by a biased allosteric mechanism, involving both G alpha q- and G alpha 12-mediated signaling pathways, and exhibited significant tocolytic activity delaying preterm labor in a mouse model (Goupil; J. Biol. Chem. 2010, 285,25624-25636), Although changes in azabicycloalkane stereochemistry and ring size caused loss of activity, replacement of the indolizidin-2-one amino acid with azaGly-Pro and azaPhe-Pro gave azapeptides 6 and 8, which reduced PGF2 alpha-induced myometrial contractions, potentiated the effect of PGF2 alpha on G alpha q-mediated ERK1/2 activation, and inhibited FP modulation of cell ruffling, a response dependent on the G alpha 12/RhoA/ROCK signaling pathway. Revealing complementarities of azabicycloalkane and azapeptide mimics, novel probes, and efficient tocolytic agents were made to study allosteric modulation of the FP receptor.

  DOI：

  10.1021/jm200608k

文献信息

• Targeting the Prostaglandin F2α Receptor for Preventing Preterm Labor with Azapeptide Tocolytics
  作者：Carine B. Bourguet、Eugénie Goupil、Danaë Tassy、Xin Hou、Eryk Thouin、Felix Polyak、Terence E. Hébert、Audrey Claing、Stéphane A. Laporte、Sylvain Chemtob、William D. Lubell

  DOI：10.1021/jm200608k

  日期：2011.9.8

  The prostaglandin-F2 alpha (PGF2 alpha) receptor (FP) was targeted to develop tocolytic agents for inhibiting preterm labor. Azabicycloalkane and azapeptide mimics 2-10 were synthesized based on the (3S,6S,9S)-indolizidin-2-one amino acid analogue PDC113.824 (1), which was shown to modulate FP by a biased allosteric mechanism, involving both G alpha q- and G alpha 12-mediated signaling pathways, and exhibited significant tocolytic activity delaying preterm labor in a mouse model (Goupil; J. Biol. Chem. 2010, 285,25624-25636), Although changes in azabicycloalkane stereochemistry and ring size caused loss of activity, replacement of the indolizidin-2-one amino acid with azaGly-Pro and azaPhe-Pro gave azapeptides 6 and 8, which reduced PGF2 alpha-induced myometrial contractions, potentiated the effect of PGF2 alpha on G alpha q-mediated ERK1/2 activation, and inhibited FP modulation of cell ruffling, a response dependent on the G alpha 12/RhoA/ROCK signaling pathway. Revealing complementarities of azabicycloalkane and azapeptide mimics, novel probes, and efficient tocolytic agents were made to study allosteric modulation of the FP receptor.