(3S)-3-[((3-(N-benzyloxycarbonyl)amino-3-methoxycarbonyl)propyl(hydroxy)phosphinyl)]-2-chloropropanoic acid | 1218782-02-5

• 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: (3S)-3-[((3-(N-benzyloxycarbonyl)amino-3-methoxycarbonyl)propyl(hydroxy)phosphinyl)]-2-chloropropanoic acid
• 英文别名: 2-chloro-3-[hydroxy-[(3S)-4-methoxy-4-oxo-3-(phenylmethoxycarbonylamino)butyl]phosphoryl]propanoic acid
• CAS: 1218782-02-5
• 化学式: C₁₆H₂₁ClNO₈P
• 分子量: 421.771
• InChiKey: GQCSLSDEGWVPHO-ABLWVSNPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  27
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  139
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (3S)-3-[((3-(N-benzyloxycarbonyl)amino-3-methoxycarbonyl)propyl(hydroxy)phosphinyl)]-2-chloropropanoic acid 在 盐酸 、 水 作用下， 以5.4 mg的产率得到LSP1-3154
  参考文献：
  名称：

  A Virtual Screening Hit Reveals New Possibilities for Developing Group III Metabotropic Glutamate Receptor Agonists

  摘要：

  (R)-PCEP (3-amino-3-carboxypropy1-2'-carboxyethyl phosphinic acid, 1), a new metabotropic glutamate receptor 4 (mGlu4R) agonist, was discovered in a previously reported virtual screening. The (S)-enantiomer and a series of derivatives were synthesized and tested on recombinant mGlu4 receptors. A large number of derivatives activated this receptor but was not able to discriminate between mGlu4 and mGlu8 receptors. The most potent ones 6 and 12 displayed an EC50 of 1.0 +/- 0.2 mu M at mGlu4R. Interestingly these agonists with longer alkyl chains revealed a new binding pocket adjacent to the glutamate binding site, which is lined with residues that differ among the mGluR subtypes and that will allow the design of more selective compounds. Additionally 6 was able to activate mGlu7 receptor with an EC50 of 43 +/- 16 mu M and is thus significantly more potent than L-AP4 (EC50 of 249 +/- 106 mu M).

  DOI：

  10.1021/jm901523t
• 作为产物：
  描述：

  ((S)-3-(((benzyloxy)carbonyl)amino)-4-methoxy-4-oxobutyl)phosphinic acid 、 2-氯丙烯酸 在 N,O-双三甲硅基乙酰胺 作用下， 以 二氯甲烷 为溶剂， 以93%的产率得到(3S)-3-[((3-(N-benzyloxycarbonyl)amino-3-methoxycarbonyl)propyl(hydroxy)phosphinyl)]-2-chloropropanoic acid
  参考文献：
  名称：

  A Virtual Screening Hit Reveals New Possibilities for Developing Group III Metabotropic Glutamate Receptor Agonists

  摘要：

  (R)-PCEP (3-amino-3-carboxypropy1-2'-carboxyethyl phosphinic acid, 1), a new metabotropic glutamate receptor 4 (mGlu4R) agonist, was discovered in a previously reported virtual screening. The (S)-enantiomer and a series of derivatives were synthesized and tested on recombinant mGlu4 receptors. A large number of derivatives activated this receptor but was not able to discriminate between mGlu4 and mGlu8 receptors. The most potent ones 6 and 12 displayed an EC50 of 1.0 +/- 0.2 mu M at mGlu4R. Interestingly these agonists with longer alkyl chains revealed a new binding pocket adjacent to the glutamate binding site, which is lined with residues that differ among the mGluR subtypes and that will allow the design of more selective compounds. Additionally 6 was able to activate mGlu7 receptor with an EC50 of 43 +/- 16 mu M and is thus significantly more potent than L-AP4 (EC50 of 249 +/- 106 mu M).

  DOI：

  10.1021/jm901523t

文献信息

• A Virtual Screening Hit Reveals New Possibilities for Developing Group III Metabotropic Glutamate Receptor Agonists
  作者：Chelliah Selvam、Nadia Oueslati、Isabelle A. Lemasson、Isabelle Brabet、Delphine Rigault、Tiphanie Courtiol、Sara Cesarini、Nicolas Triballeau、Hugues-Olivier Bertrand、Cyril Goudet、Jean-Philippe Pin、Francine C. Acher

  DOI：10.1021/jm901523t

  日期：2010.4.8

  (R)-PCEP (3-amino-3-carboxypropy1-2'-carboxyethyl phosphinic acid, 1), a new metabotropic glutamate receptor 4 (mGlu4R) agonist, was discovered in a previously reported virtual screening. The (S)-enantiomer and a series of derivatives were synthesized and tested on recombinant mGlu4 receptors. A large number of derivatives activated this receptor but was not able to discriminate between mGlu4 and mGlu8 receptors. The most potent ones 6 and 12 displayed an EC50 of 1.0 +/- 0.2 mu M at mGlu4R. Interestingly these agonists with longer alkyl chains revealed a new binding pocket adjacent to the glutamate binding site, which is lined with residues that differ among the mGluR subtypes and that will allow the design of more selective compounds. Additionally 6 was able to activate mGlu7 receptor with an EC50 of 43 +/- 16 mu M and is thus significantly more potent than L-AP4 (EC50 of 249 +/- 106 mu M).