(S)-1-(2-氨基-2-羧乙基)-3-(2-羧苄基)嘧啶-2,4-二酮 | 745055-91-8

• 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
• 中文名称: (S)-1-(2-氨基-2-羧乙基)-3-(2-羧苄基)嘧啶-2,4-二酮
• 英文名称: UBP 302
• 英文别名: (S)-3-(2-carboxybenzyl)willardiine；(S)-1-(2-Amino-2-carboxyethyl)-3-(2-carboxybenzyl)pyrimidine-2,4-dione；2-[[3-[(2S)-2-amino-2-carboxyethyl]-2,6-dioxopyrimidin-1-yl]methyl]benzoic acid
• CAS: 745055-91-8
• 化学式: C₁₅H₁₅N₃O₆
• 分子量: 333.301
• InChiKey: UUIYULWYHDSXHL-NSHDSACASA-N

物化性质

• 熔点：
  207.9-208.5 °C (decomp)(Solv: water (7732-18-5))
• 沸点：
  603.0±65.0 °C(Predicted)
• 密度：
  1.525±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO: ≥5mg/mL， 60°C (加热5分钟)

计算性质

• 辛醇/水分配系数(LogP)：
  -3.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  141
• 氢给体数：
  3
• 氢受体数：
  7

制备方法与用途

生物活性

UBP 302 是一种有效且选择性的 GLUK5-subunit containing kainate receptor 拮抗剂（表观 Kd=402 nM），对 GluK2 (GluR6) kainate receptors 的亲和力很小，具有抗焦虑作用。

靶点

• apparent Kd: 402 nM (GLUK5)
• IC50: 106 μM (AMPA receptors)

反应信息

• 作为反应物：
  描述：

  (S)-1-(2-氨基-2-羧乙基)-3-(2-羧苄基)嘧啶-2,4-二酮 在 溴 、 溶剂黄146 作用下， 反应 18.5h， 生成 (S)-1-(2-amino-2-carboxyethyl)-5-bromo-3-(2-carboxybenzyl)-pyrimidine-2,4-dione 、 (R)-1-(2-amino-2-carboxyethyl)-3-(2-carboxybenzyl)-5-bromopyrimidine-2,4-dione
  参考文献：
  名称：

  Synthesis and Pharmacological Characterization of N³-Substituted Willardiine Derivatives:  Role of the Substituent at the 5-Position of the Uracil Ring in the Development of Highly Potent and Selective GLU_K5 Kainate Receptor Antagonists

  摘要：

  Some N-3-substituted analogues of willardiine such as 11 and 13 are selective kainate receptor antagonists. In an attempt to improve the potency and selectivity for kainate receptors, a range of analogues of 11 and 13 were synthesized with 5-substituents on the uracil ring. An X-ray crystal structure of the 5-methyl analogue of 13 bound to GLU(K5) revealed that there was allowed volume around the 4- and 5-positions of the thiophene ring, and therefore the 4,5-dibromo and 5-phenyl (67) analogues were synthesized. Compound 67 (ACET) demonstrated low nanomolar antagonist potency on native and recombinant GLU(K5)-containing kainate receptors (K-B values of 7 +/- 1 and 5 +/- 1 nM for antagonism of recombinant human GLU(K5) and GLU(K5)/GLU(K2), respectively) but displayed IC50 values > 100 mu M for antagonism of GLU(A2), GLU(K6), or GLU(K6)/GLU(K2).

  DOI：

  10.1021/jm061041u

文献信息

• DIMERIC IAP INHIBITORS
  申请人：STRAUB Christopher Sean

  公开号：US20110206690A1

  公开（公告）日：2011-08-25

  The present invention provides compounds of formula M-L-M′ (where M and M′ are each independently a monomeric moiety of Formula (I) and L is a linker). The dimeric compounds have been found to be effective in promoting apoptosis in rapidly dividing cells.

  本发明提供了公式M-L-M′的化合物（其中M和M′分别是公式（I）中的单体基团，L是连接物）。已发现二聚化合物在促进快速分裂细胞凋亡方面具有有效性。
• US8445440B2
  申请人：——

  公开号：US8445440B2

  公开（公告）日：2013-05-21
• [EN] DIMERIC IAP INHIBITORS<br/>[FR] INHIBITEURS DIMÈRES D'IAP
  申请人：NOVARTIS AG

  公开号：WO2011104266A1

  公开（公告）日：2011-09-01

  The present invention provides compounds of formula M-L-M' (where M and M' are each independently a monomeric moiety of Formula (I) and L is a linker). The dimeric compounds have been found to be effective in promoting apoptosis in rapidly dividing cells.
• Synthesis and Pharmacological Characterization of N³-Substituted Willardiine Derivatives:  Role of the Substituent at the 5-Position of the Uracil Ring in the Development of Highly Potent and Selective GLU_K5 Kainate Receptor Antagonists
  作者：Nigel P. Dolman、Julia C. A. More、Andrew Alt、Jody L. Knauss、Olli T. Pentikäinen、Carla R. Glasser、David Bleakman、Mark L. Mayer、Graham L. Collingridge、David E. Jane

  DOI：10.1021/jm061041u

  日期：2007.4.1

  Some N-3-substituted analogues of willardiine such as 11 and 13 are selective kainate receptor antagonists. In an attempt to improve the potency and selectivity for kainate receptors, a range of analogues of 11 and 13 were synthesized with 5-substituents on the uracil ring. An X-ray crystal structure of the 5-methyl analogue of 13 bound to GLU(K5) revealed that there was allowed volume around the 4- and 5-positions of the thiophene ring, and therefore the 4,5-dibromo and 5-phenyl (67) analogues were synthesized. Compound 67 (ACET) demonstrated low nanomolar antagonist potency on native and recombinant GLU(K5)-containing kainate receptors (K-B values of 7 +/- 1 and 5 +/- 1 nM for antagonism of recombinant human GLU(K5) and GLU(K5)/GLU(K2), respectively) but displayed IC50 values > 100 mu M for antagonism of GLU(A2), GLU(K6), or GLU(K6)/GLU(K2).