rac-2-benzyloxycarbonylamino-3-methoxycarbonylaminopropionic acid | 1182348-91-9

• 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: rac-2-benzyloxycarbonylamino-3-methoxycarbonylaminopropionic acid
• 英文别名: 3-(Methoxycarbonylamino)-2-(phenylmethoxycarbonylamino)propanoic acid
• CAS: 1182348-91-9
• 化学式: C₁₃H₁₆N₂O₆
• 分子量: 296.28
• InChiKey: NNBFAFNXVKNPDN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  21
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  114
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  rac-2-benzyloxycarbonylamino-3-methoxycarbonylaminopropionic acid 在 5%-palladium/activated carbon 、 氢气 作用下， 以 四氢呋喃 、 水 为溶剂， 以54%的产率得到rac-2-amino-3-methoxycarbonylaminopropionic acid
  参考文献：
  名称：

  Drug Design, in Vitro Pharmacology, and Structure−Activity Relationships of 3-Acylamino-2-aminopropionic Acid Derivatives, a Novel Class of Partial Agonists at the Glycine Site on the N-Methyl-d-aspartate (NMDA) Receptor Complex

  摘要：

  Retaining agonistic activity at the glycine coagonist site of the NMDA receptor in molecules derived from glycine or D-serine has proven to be difficult because in the vicinity of the alpha-amino acid group little substitution is tolerated. We have solved this problem by replacing the hydroxy group of D-serine with an amido group, thus keeping the hydrogen donor function and allowing For further substitution and exploration of the adjacent space. Heterocyclic substitutions resulted in a series of 3-acylamino-2-aminopropionic acid derivatives, with high affinities in a binding assay for the glycine site. In a functional assay assessing the activation of the glycine site, these compounds displayed a wide range of intrinsic efficacies, from antagonism to a high degree of partial agonism. Structure-activity relationships reveal that lipophilic substituents, presumably filling an additional hydrophobic pocket, are accepted by the glycine site, provided that they are separated from the alpha-amino acid group by a short linker.

  DOI：

  10.1021/jm900363q
• 作为产物：
  描述：

  3-amino-2-(benzyloxycarbonylamino)propionic acid 、 氯甲酸甲酯 在 碳酸氢钠 、 sodium hydroxide 、 盐酸 、 水 作用下， 以 甲苯 、 四氢呋喃 、 乙醚 为溶剂， 反应 2.17h， 以100%的产率得到rac-2-benzyloxycarbonylamino-3-methoxycarbonylaminopropionic acid
  参考文献：
  名称：

  Drug Design, in Vitro Pharmacology, and Structure−Activity Relationships of 3-Acylamino-2-aminopropionic Acid Derivatives, a Novel Class of Partial Agonists at the Glycine Site on the N-Methyl-d-aspartate (NMDA) Receptor Complex

  摘要：

  Retaining agonistic activity at the glycine coagonist site of the NMDA receptor in molecules derived from glycine or D-serine has proven to be difficult because in the vicinity of the alpha-amino acid group little substitution is tolerated. We have solved this problem by replacing the hydroxy group of D-serine with an amido group, thus keeping the hydrogen donor function and allowing For further substitution and exploration of the adjacent space. Heterocyclic substitutions resulted in a series of 3-acylamino-2-aminopropionic acid derivatives, with high affinities in a binding assay for the glycine site. In a functional assay assessing the activation of the glycine site, these compounds displayed a wide range of intrinsic efficacies, from antagonism to a high degree of partial agonism. Structure-activity relationships reveal that lipophilic substituents, presumably filling an additional hydrophobic pocket, are accepted by the glycine site, provided that they are separated from the alpha-amino acid group by a short linker.

  DOI：

  10.1021/jm900363q

文献信息

• [EN] ANTHRANILIC ACID DERIVATIVES AS INHIBITORS OF THE CGMP-PHOSPHODIESTERASE<br/>[FR] DERIVES D'ACIDE ANTHRANILIQUE UTILISES COMME INHIBITEURS DE LA CGMP-PHOSPHODIESTERASE
  申请人：FUJISAWA PHARMACEUTICAL CO

  公开号：WO2001030745A1

  公开（公告）日：2001-05-03

  This invention relates to a compound of formula (I): wherein R1 is nitro group, amino group, cyano group, a halo(lower)alkyl group, a halogen atom, etc., R2 is an optionally substituted aryl group, A is a lower alkylene group, and R3 is an optionally substituted heterocyclic group, or a group of formula: -CR4R5R6, in which R?4 and R5¿ are each independently an optionally substituted carbamoyl group or an optionally substituted lower alkyl group, or R?4 and R5¿ together with the carbon atom to which R?4 and R5¿ are attached may form an optionally substituted carbocyclic group, and R6 is hydrogen atom or a lower alkyl group, etc., and a prodrug and a acceptable salt thereof, to processes for preparation thereof, to a pharmaceutical composition containing the same, and to a method for the prevention and/or the treatment of various diseases, such as erectile dysfunction.
• Drug Design, in Vitro Pharmacology, and Structure−Activity Relationships of 3-Acylamino-2-aminopropionic Acid Derivatives, a Novel Class of Partial Agonists at the Glycine Site on the <i>N</i>-Methyl-<scp>d</scp>-aspartate (NMDA) Receptor Complex
  作者：Stephan Urwyler、Philipp Floersheim、Bernard L. Roy、Manuel Koller

  DOI：10.1021/jm900363q

  日期：2009.8.27

  Retaining agonistic activity at the glycine coagonist site of the NMDA receptor in molecules derived from glycine or D-serine has proven to be difficult because in the vicinity of the alpha-amino acid group little substitution is tolerated. We have solved this problem by replacing the hydroxy group of D-serine with an amido group, thus keeping the hydrogen donor function and allowing For further substitution and exploration of the adjacent space. Heterocyclic substitutions resulted in a series of 3-acylamino-2-aminopropionic acid derivatives, with high affinities in a binding assay for the glycine site. In a functional assay assessing the activation of the glycine site, these compounds displayed a wide range of intrinsic efficacies, from antagonism to a high degree of partial agonism. Structure-activity relationships reveal that lipophilic substituents, presumably filling an additional hydrophobic pocket, are accepted by the glycine site, provided that they are separated from the alpha-amino acid group by a short linker.