- Structural evaluation and electrophysiological effects of some kynurenic acid analogs
-
Kynurenic acid (KYNA), a metabolite of tryptophan, as an excitatory amino acid receptor antagonist is an effective neuroprotective agent in case of excitotoxicity, which is the hallmark of brain ischemia and several neurodegenerative processes. Therefore, kynurenine pathway, KYNA itself, and its derivatives came into the focus of research. During the past fifteen years, our research group has developed several neuroactive KYNA derivatives, some of which proved to be neuroprotective in preclinical studies. In this study, the synthesis of these KYNA derivatives and their evaluation with divergent molecular characteristics are presented together with their most typical effects on the monosynaptic transmission in CA1 region of the hippocampus of the rat. Their effects on the basic neuronal activity (on the field excitatory postsynaptic potentials: fEPSP) were studied in in vitro hippocampal slices in 1 and 200 μM concentrations. KYNA and its derivative 4 in both 1 and 200 μM concentrations proved to be inhibitory, while derivative 8 only in 200 μM decreased the amplitudes of fEPSPs. Derivative 5 facilitated the fEPSPs in 200 μM concentration. This is the first comparative study which evaluates the structural and functional differences of formerly and newly developed KYNA analogs. Considerations on possible relations between molecular structures and their physiological effects are presented.
- Fehér, Evelin,Szatmári, István,Dudás, Tamás,Zalatnai, Anna,Farkas, Tamás,Orinczi, Bálint L.,Fül?p, Ferenc,Vécsei, László,Toldi, József
-
-
Read Online
- Late stage iodination of biologically active agents using a one-pot process from aryl amines
-
A simple and effective one-pot tandem procedure that generates aryl iodides from readily available aryl amines via stable diazonium salts has been developed. The operationally simple procedure and mild conditions allow late-stage iodination of a wide range of aryl compounds bearing various functional groups and substitution patterns. A novel synthetic strategy involving the preparation of nitroaryl compounds followed by a chemoselective tin(ii) dichloride reduction and the use of the one-pot diazotisation-iodination transformation was also developed. The general applicability of this approach was demonstrated with the preparation of a number of medicinally important compounds including CNS1261, a SPECT imaging agent of the N-methyl-d-aspartate (NMDA) receptor and IBOX, a compound used to detect amyloid plaques in the brain.
- Sloan, Nikki L.,Luthra, Sajinder K.,McRobbie, Graeme,Pimlott, Sally L.,Sutherland, Andrew
-
p. 54881 - 54891
(2017/12/12)
-
- Structure-activity relationships of novel iodinated quinoline-2- carboxamides for targeting the translocator protein
-
In an effort to develop a new SPECT imaging agent for the translocator protein (TSPO), a series of novel iodinated quinoline-2-carboxamides have been synthesised and evaluated for binding affinity using rat brain homogenates. The outcome of the biological testing in combination with HPLC determination of the physicochemical properties of these compounds directed the design of new analogues resulting in 4-(2-iodophenyl)quinoline-2-N-diethylcarboxamide, a new TSPO ligand with higher affinity than the widely used clinical imaging agent PK11195.
- Blair, Adele,Stevenson, Louise,Dewar, Deborah,Pimlott, Sally L.,Sutherland, Andrew
-
p. 1461 - 1466
(2013/11/19)
-
- New iodinated quinoline-2-carboxamides for SPECT imaging of the translocator protein
-
With the aim of developing new SPECT imaging agents for the translocator protein (TSPO), a small library of iodinated quinoline-2-carboxamides have been prepared and tested for binding affinity with TSPO. N,N-Diethyl-3-iodomethyl-4-phenylquinoline-2-carboxamide was found to have excellent affinity (Ki 12.0 nM), comparable to that of the widely used TSPO imaging agent PK11195.
- Stevenson, Louise,Tavares, Adriana A.S.,Brunet, Aurelie,McGonagle, Fiona I.,Dewar, Deborah,Pimlott, Sally L.,Sutherland, Andrew
-
supporting information; experimental part
p. 954 - 957
(2010/06/11)
-
