PDC113.824 | 634586-78-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: PDC113.824
• 英文别名: (3S)-3-[[(2S)-2-[[(3S,6S,8aS)-5-oxo-6-[(2-phenylacetyl)amino]-2,3,6,7,8,8a-hexahydro-1H-indolizine-3-carbonyl]amino]-3-pyridin-3-ylpropanoyl]amino]-4-phenylbutanoic acid
• CAS: 634586-78-0
• 化学式: C₃₅H₃₉N₅O₆
• 分子量: 625.725
• InChiKey: HICVXOMTGSGJJZ-IIZANFQQSA-N

物化性质

• 沸点：
  1020.4±65.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  46
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  158
• 氢给体数：
  4
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  benzyl (3S)-3-[[(2S)-2-[[(3S,6S,8aS)-5-oxo-6-[(2-phenylacetyl)amino]-2,3,6,7,8,8a-hexahydro-1H-indolizine-3-carbonyl]amino]-3-pyridin-3-ylpropanoyl]amino]-4-phenylbutanoate 在 palladium 10% on activated carbon 、 氢气 、 溶剂黄146 作用下， 以 乙醇 为溶剂， 以2%的产率得到PDC113.824
  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

• PROSTAGLANDIN-F2 ALPHA RECEPTOR MODULATORS AND USES THEREOF
  申请人：LUBELL William D.

  公开号：US20120309690A1

  公开（公告）日：2012-12-06

  Prostaglandin-F2 alpha (PGF2α) receptor (FP) modulators of formula I, as well as the use of PGF2α receptor modulators for the treatment of conditions associated with FP activity such as preterm labor and colorectal cancer, are disclosed.

  本文揭示了公式I的前列腺素F2α（PGF2α）受体（FP）调节剂，以及使用PGF2α受体调节剂治疗与FP活性相关的疾病，例如早产和结直肠癌的方法。
• US8802818B2
  申请人：——

  公开号：US8802818B2

  公开（公告）日：2014-08-12
• US9073963B2
  申请人：——

  公开号：US9073963B2

  公开（公告）日：2015-07-07
• 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.