140187-23-1

Basic information

• Product Name: (S)-(-)-5-FLUOROWILLARDIINE
• Synonyms: 5-fluorowillardiine;(S)-(-)-5-FLUOROWILLARDIINE;(S)-(-)-ALPHA-AMINO-5-FLUORO-3,4-DIHYDRO-2,4-DIOXO-1(2H)PYRIDINEPROPANOIC ACID;WILLARDIINE, S(-)-5-FLUORO POTENT AMPA/K AINATE A;(S)-(-)-alpha-Amino-5-fluoro-3,4-dihydro-2,4-dioxo-1(2H)-pyrimmidinepropanoic acid;(S)-(-)-α-Amino-5-fluoro-3,4-dihydro-2,4-dioxo-1(2H)pyridinepropanoicacid;(αS)-α-Amino-5-fluoro-3,4-dihydro-2,4-dioxo-1(2H)-pyrimidinepropanoic acid;3-(5-fluorouracil-1-yl)-L-alanine
• CAS NO: 140187-23-1
• Molecular Formula: C7H8FN3O4
• Molecular Weight: 217.15
• Product Categories: Glutamate receptor;Glutamate
• Mol File: 140187-23-1.mol
• Article Data: 1

Chemical Properties

• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: off-white Solid
• Density: 1.64 g/cm³
• Refractive Index: 1.601
• Storage Temp.: Store at RT
• Solubility: Aqueous Acid (Slightly)
• CAS DataBase Reference: (S)-(-)-5-FLUOROWILLARDIINE(CAS DataBase Reference)
• NIST Chemistry Reference: (S)-(-)-5-FLUOROWILLARDIINE(140187-23-1)
• EPA Substance Registry System: (S)-(-)-5-FLUOROWILLARDIINE(140187-23-1)

Safety Data

• Hazardous Substances Data: 140187-23-1(Hazardous Substances Data)

Usage

Uses

(S)-(-)-5-Fluorowillardiine is a potent and selective AMPA receptor agonist at hGluR1 and hGluR2 (1,2).

Definition

ChEBI: An alanine derivative that is L-alanine bearing a 5-fluorouracil-1-yl substituent at position 3. A more potent and selective AMPA receptor agonist (at hGluR1 and hGluR2) than AMPA itself (Ki = 14.7, 25.1, and 1820 nM for hGluR1, hGluR2 and hGluR5 respectively).

Biological Activity

A more potent and selective AMPA receptor agonist (at hGluR1 and hGluR2) than AMPA itself (K i = 14.7, 25.1, and 1820 nM for hGluR1, hGluR2 and hGluR5 respectively). Also available as part of the AMPA Receptor Tocriset? .

InChI:InChI=1/C7H8FN3O4/c8-3-1-11(2-4(9)6(13)14)7(15)10-5(3)12/h1,4H,2,9H2,(H,13,14)(H,10,12,15)/t4-/m0/s1

Relevant articles and documents

Synthesis of Willardiine and 6-azawillardiine analogs: Pharmacological characterization on cloned homomeric human AMPA and kainate receptor subtypes

Both willardiine and azawillardiine analogs (18-28) have been reported to be potent and selective agonists for either AMPA or kainate receptors. We report here the novel synthesis and pharmacological characterization of a range of willardiine (18-23) and 6-azawillardiine (24-28) analogs on cells individually expressing human homomeric hGluR1, hGluR2, hGluR4, or hGluR5 receptors. Reaction of the sodium salts of substituted uracils (7-12) or 6- azauracils (13-16) with (S)-3-[(tert-butoxycarbonyl)amino]oxetan-2-one (17) in dry DMF, subsequent deprotection in TFA, and purification by ion-exchange chromatography gave mainly the willardiine analog in which alkylation took place on N1 of the uracil ring. We have investigated the subtype selectivity of these compounds by examining their binding affinity for homomeric hGluR1, -2, -4, or -5 (and hGluR6 in the case of 5-iodowillardiine (22)). From this study we have demonstrated that 22 has high affinity for hGluR5 and, compared to kainate, displays excellent selectivity for this receptor over both the AMPA receptor subtypes and the homomeric kainate receptor, hGluR6. 5- Fluorowillardiine (19) has higher affinity than AMPA for both homomeric hGluR1 and hGluR2 and compared to AMPA displays greater selectivity for AMPA receptor subtypes over the kainate receptor, hGluR5. Some structural features required for optimal activity at homomeric AMPA or kainate receptor subtypes have also been identified. It would appear that quite large lipophilic substituents at the 5-position of the uracil ring not only are accommodated by hGluR5 receptors but also lead to enhanced affinity for these receptors. In contrast to this, for optimal binding affinity to hGluR1, -2, or -4, smaller, electron-withdrawing substituents are required. For optimal activity at hGluR4 receptors a 6-azasubstituted willardiine is favored. The subtype- selective compounds described here are likely to be useful tools to probe the distribution and the physiological roles of the various glutamate receptor subunits in the central nervous system.