[(3S)-3-(N-benzyloxycarbonyl)amino-3-methoxycarbonylpropyl][(3-nitrophenyl)((N-benzyloxycarbonyl)amino)methyl]phosphinic acid | 1245939-23-4

• 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-(N-benzyloxycarbonyl)amino-3-methoxycarbonylpropyl][(3-nitrophenyl)((N-benzyloxycarbonyl)amino)methyl]phosphinic acid
• 英文别名: (benzyloxycarbonylamino)(3-nitrophenyl)-methyl-((S)-3-(benzyloxycarbonylamino)-3-(methoxycarbonyl)propyl)-phosphinic acid；[(3S)-4-methoxy-4-oxo-3-(phenylmethoxycarbonylamino)butyl]-[(3-nitrophenyl)-(phenylmethoxycarbonylamino)methyl]phosphinic acid
• CAS: 1245939-23-4
• 化学式: C₂₈H₃₀N₃O₁₀P
• 分子量: 599.534
• InChiKey: SVBGFRNYRYHLPI-SKCDSABHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  42
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  186
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  [(3S)-3-(N-benzyloxycarbonyl)amino-3-methoxycarbonylpropyl][(3-nitrophenyl)((N-benzyloxycarbonyl)amino)methyl]phosphinic acid 在 盐酸 作用下， 反应 5.0h， 以3.3 mg的产率得到[(3S)-3-amino-3-carboxypropyl][(3-nitrophenyl)-(aminomethyl)]phosphinic acid
  参考文献：
  名称：

  Increased Potency and Selectivity for Group III Metabotropic Glutamate Receptor Agonists Binding at Dual sites

  摘要：

  A group III metabotropic glutamate (mGlu) receptor agonist (PCEP) was identified by virtual HTS. This orthosteric ligand is composed by an L-AP4-derived fragment that mimics glutamate and a chain that binds into a neighboring pocket, offering possibilities to improve affinity and selectivity. Herein we describe a series of derivatives where the distal chain is replaced by an aromatic or heteroaromatic group. Potent agonists were identified, including some with a mGlu(4) subtype preference, e.g., 17m (LSP1-2111) and 16g (LSP4-2022). Molecular modeling suggests that aromatic functional groups may bind at either one of the two chloride regulatory sites. These agonists may thus be considered as particular bitopic/dualsteric ligands. 17m was shown to reduce GABAergic synaptic transmission at striatopallidal synapses. We now demonstrate its inhibitory effect at glutamatergic parallel fiber-Purkinje cell synapses in the cerebellar cortex. Although these ligands have physicochemical properties that are markedly different from typical CNS drugs, they hold significant therapeutic potential.

  DOI：

  10.1021/acs.jmedchem.7b01438
• 作为产物：
  描述：

  (S)-2-(苄氧羰氨基)-3-丁烯酸甲酯 在 次磷酸 、 乙酰氯 作用下， 以 溶剂黄146 为溶剂， 反应 5.0h， 生成 [(3S)-3-(N-benzyloxycarbonyl)amino-3-methoxycarbonylpropyl][(3-nitrophenyl)((N-benzyloxycarbonyl)amino)methyl]phosphinic acid
  参考文献：
  名称：

  Increased Potency and Selectivity for Group III Metabotropic Glutamate Receptor Agonists Binding at Dual sites

  摘要：

  A group III metabotropic glutamate (mGlu) receptor agonist (PCEP) was identified by virtual HTS. This orthosteric ligand is composed by an L-AP4-derived fragment that mimics glutamate and a chain that binds into a neighboring pocket, offering possibilities to improve affinity and selectivity. Herein we describe a series of derivatives where the distal chain is replaced by an aromatic or heteroaromatic group. Potent agonists were identified, including some with a mGlu(4) subtype preference, e.g., 17m (LSP1-2111) and 16g (LSP4-2022). Molecular modeling suggests that aromatic functional groups may bind at either one of the two chloride regulatory sites. These agonists may thus be considered as particular bitopic/dualsteric ligands. 17m was shown to reduce GABAergic synaptic transmission at striatopallidal synapses. We now demonstrate its inhibitory effect at glutamatergic parallel fiber-Purkinje cell synapses in the cerebellar cortex. Although these ligands have physicochemical properties that are markedly different from typical CNS drugs, they hold significant therapeutic potential.

  DOI：

  10.1021/acs.jmedchem.7b01438

文献信息

• [EN] DIASTEREOISOMERS OF HYPOPHOSPHOROUS ACID DERIVATIVES<br/>[FR] DIASTÉRÉOISOMÈRES DE DÉRIVÉS D'ACIDE HYPOPHOSPHOREUX
  申请人：CENTRE NAT RECH SCIENT

  公开号：WO2010106526A1

  公开（公告）日：2010-09-23

  The invention relates to the diastereoisomers of hypophosphorous acid derivatives, having formula (I), wherein the phenyl group is substituted by one or several atoms or groups, occupying one or several positions on the phenyl ring, and a method for the separation thereof.

  该发明涉及具有式（I）的次磷酸衍生物的对映异构体，其中苯基被一个或多个原子或基团取代，占据苯环上的一个或多个位置，并提供了一种分离它们的方法。
• DIASTEREOISOMERS OF HYPOPHOSPHOROUS ACID DERIVATIVES
  申请人：Centre National de la Recherche Scientifique CNRS

  公开号：EP2408789A1

  公开（公告）日：2012-01-25
• Increased Potency and Selectivity for Group III Metabotropic Glutamate Receptor Agonists Binding at Dual sites
  作者：Chelliah Selvam、Isabelle A. Lemasson、Isabelle Brabet、Nadia Oueslati、Berin Karaman、Alexandre Cabaye、Amélie S. Tora、Bruno Commare、Tiphanie Courtiol、Sara Cesarini、Isabelle McCort-Tranchepain、Delphine Rigault、Laetitia Mony、Thomas Bessiron、Heather McLean、Frédéric R. Leroux、Françoise Colobert、Hervé Daniel、Anne Goupil-Lamy、Hugues-Olivier Bertrand、Cyril Goudet、Jean-Philippe Pin、Francine C. Acher

  DOI：10.1021/acs.jmedchem.7b01438

  日期：2018.3.8

  A group III metabotropic glutamate (mGlu) receptor agonist (PCEP) was identified by virtual HTS. This orthosteric ligand is composed by an L-AP4-derived fragment that mimics glutamate and a chain that binds into a neighboring pocket, offering possibilities to improve affinity and selectivity. Herein we describe a series of derivatives where the distal chain is replaced by an aromatic or heteroaromatic group. Potent agonists were identified, including some with a mGlu(4) subtype preference, e.g., 17m (LSP1-2111) and 16g (LSP4-2022). Molecular modeling suggests that aromatic functional groups may bind at either one of the two chloride regulatory sites. These agonists may thus be considered as particular bitopic/dualsteric ligands. 17m was shown to reduce GABAergic synaptic transmission at striatopallidal synapses. We now demonstrate its inhibitory effect at glutamatergic parallel fiber-Purkinje cell synapses in the cerebellar cortex. Although these ligands have physicochemical properties that are markedly different from typical CNS drugs, they hold significant therapeutic potential.