5-fluorowillardiine 5-fluorowillardiine 5-fluorowillardiine is a selective agonist for the ampa receptor, with only limited effects at the kainate receptor. it is an excitotoxic neurotoxin when used in vivo and so is rarely used in intact animals, but it is widely used to selectively stimulate ampa receptors in vitro. it is structurally similar to the compound willardiine, which is also an agonist for the ampa and kainate receptors. willardiine occurs naturally in mariosousa willardiana and acacia sensu lato. 5-fluorowillardiine names other names 2-amino-3-(5-fluoro-2,4-dioxopyrimidin-1-yl)propanoic acid identifiers cas number 140187-23-1 (s) n 3d model (jsmol) interactive image chebi chebi:42549 n chembl chembl123132 n chemspider 1259 y112461 (s) y drugbank db02966 n echa infocard 100.162.280 pubchem cid 1299126569 (s) unii 7ctr2lwv5m y comptox dashboard (epa) dtxsid1042609 inchi inchi=1s/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) ykey: dbwpfhjystvbcz-uhfffaoysa-n yinchi=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)key: dbwpfhjystvbcz-uhfffaoyar smiles nc(cn1c=c(f)c(=o)n=c1o)c(o)=o properties chemical formula c7h8fn3o4 molar mass 217.156 g·mol−1 log p -1.168 acidity (pka) 2.118 basicity (pkb) 11.879 isoelectric point 4.28 except where otherwise noted, data are given for materials in their standard state (at 25 °c , 100 kpa). n verify (what is yn ?) infobox references the name is unusual as it has two successive i's. this is not a typo. toxicity (s)-5-fluorowillardiine activity has been studied in vitro in a variety of neural tissues. in mouse embryo hippocampal neurons, it was found to desensitize ampa/kainate receptors with an ec50 of 1.5 μm –— 7 times more potent than racemic ampa (ec50 of 11 μm). in another study, (s)-5-fluorowillardiine showed biphasic dose-dependent neurotoxicity in cultural rodent cortical neurons, with ec50 vales of 0.70 and 170 μm. while in vivo research is sparse, a study in 5-day-old mice injected with the closely related ampa/kainate agonist (s)-5-bromowillardiine showed cortical and white matter damage. ampa antagonists reduced the extent of the damage in a dose-dependent fashion. applications in research radiolabeled 5-fluorowillardiine has been used to study the distribution of ionotropic glutamate receptors in rodent brains. it has also been used to evaluate the effects of various allosteric modulators of the ampa receptor. chemistry structure and activity synthesis of 5-fluorowillardiine 5-fluorowillardiine is derived from the nitrogenous base uracil found in rna. it is one member of a family of willardiine compounds, which share uracil or a substituted uracil as an amino acid side chain. 5-fluorowillardiine exists as two distinct isomers: (2r) or d (2s) or l the particularly high affinity of 5-fluorowillardiine for the ampa receptor is attributed to its fluorine substituent at the 5-position of the ring, which is electron-withdrawing and small enough to not interfere with binding. by contrast, related willardiine derivatives with larger nonpolar electron withdrawing groups exhibit greater affinity for kainate receptors than 5-fluorowillardiine, and less affinity for ampa receptors. the binding of 5-fluorowillardiine to the ampa receptor is driven by entropy when its ring is uncharged. when the ring is deprotonated and has a negative charge, a favorable change in enthalpy primarily drives binding. because the pka values of halogenated willardiine derivates are approximately 8 (7.98 for 5-fluorowillardiine), binding is mostly driven by an increase in entropy at physiological ph. synthesis the synthesis of 5-fluorowillardiine may be achieved by using 5-fluorouracil as a nucleophile to open a specialized lactone in an sn2 reaction. another straightforward approach is to perform a strecker amino acid synthesis.