Radiosynthesis of novel18F-labelled derivatives of indiplon as potential GABAA receptor imaging tracers for PET

2008 ◽  
Vol 51 (3) ◽  
pp. 123-131 ◽  
Author(s):  
Steffen Fischer ◽  
Achim Hiller ◽  
Matthias Scheunemann ◽  
Winnie Deuther-Conrad ◽  
Alexander Hoepping ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Receptor Imaging ◽  
Derivatives Of

3-Aminomethyl Derivatives of 2-Phenylimidazo[1,2-a]-pyridine as Positive Allosteric Modulators of GABAA Receptor with Potential Antipsychotic Activity

2017 ◽  
Vol 8 (6) ◽  
pp. 1291-1298 ◽  
Author(s):  
Monika Marcinkowska ◽  
Marcin Kołaczkowski ◽  
Krzysztof Kamiński ◽  
Adam Bucki ◽  
Maciej Pawłowski ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Allosteric Modulators ◽  
Antipsychotic Activity ◽  
Aminomethyl Derivatives ◽  
Positive Allosteric Modulators ◽  
Derivatives Of

Synthesis and Evaluation of α-Asaronol Esters with LDH and GABAA Receptor Modulation as Anticonvulsant Agents

2020 ◽  
Vol 17 (7) ◽  
pp. 891-904
Author(s):  
Yajun Bai ◽  
Bin Li ◽  
Jing Xie ◽  
Xufei Chen ◽  
Shu Cheng ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
Chloride Ion ◽  
Neuroprotective Effects ◽  
Receptor Modulation ◽  
Chloride Ion Influx ◽  
Weak Activity ◽  
Ion Influx ◽  
Low Toxicity ◽  
Derivatives Of

Background: Our previous studies showed that α-asaronol was a potential antiepileptic candidate. Here, twelve O-terminus modified ester derivatives of α-asaronol were designed, synthesized and evaluated their anticonvulsant activity. Methods: All synthetic compounds were subjected to three animal models of seizure (MES, scPTZ and sc3-MP models) combined with neurotoxicity test, as well as the LDH inhibitory test. Furthermore, GABAA Receptor modulation and pharmacokinetic evaluation of compound 4k were also performed. Results: Five compounds (4a, 4b, 4d, 4e and 4k) showed significant anticonvulsant properties at the dose of 30-300 mg/kg in MES and scPTZ test, but weak activity in sc3-MP model. Meanwhile, 4a, 4b, 4d and 4k showed good LDH inhibitory activity in vitro. Specifically, 4k was the best compound in above evaluation, and better than that of α-asaronol and reference compound (stiripentol). In addition, 4k could increase chloride ion influx by modulating GABAA receptor α1β2γ2 subtype with EC50 of 48.65 ± 10.31 μM and showed good PK profiles in rats with moderate oral bioavailability (51.5%). Conclusion: These results suggested 4k possesses potential effectiveness in treatment of therapyresistant seizures and is expected to be developed as a novel molecule for safer and efficient anticonvulsants having neuroprotective effects as well as low toxicity.

GABAA receptor pharmacology of fluorinated derivatives of the novel sedative-hypnotic pyrazolopyrimidine indiplon

2008 ◽  
Vol 580 (1-2) ◽  
pp. 1-11 ◽  
Author(s):  
Florian Wegner ◽  
Winnie Deuther-Conrad ◽  
Matthias Scheunemann ◽  
Peter Brust ◽  
Steffen Fischer ◽  
...  
Keyword(s):  
Gabaa Receptor ◽  
The Novel ◽  
Receptor Pharmacology ◽  
Fluorinated Derivatives ◽  
Derivatives Of

scholarly journals MOLECULAR DESIGN OF N-ACYL DERIVATIVES OF 2-(2-OXOPYROLIDIN-1-YL)-ACETAMIDE WITH GABA-ERGIC AND GLUTAMATERGIC ACTIVITIES

2021 ◽  
Vol 9 (1) ◽  
pp. 84-97
Author(s):  
I. P. Kodonidi ◽  
A. S. Chiriapkin ◽  
D. E. Tworowski
Keyword(s):  
Molecular Docking ◽  
Binding Site ◽  
Gabaa Receptor ◽  
Ampa Receptors ◽  
Molecular Design ◽  
Nootropic Activity ◽  
Gamma Aminobutyric Acid ◽  
Identification Code ◽  
Derivatives Of ◽  
Acyl Derivatives

The first of the most successfully implemented nootropic drugs in medical practice is piracetam, which should be attributed to cyclic derivatives of gamma-aminobutyric acid. The production of new piracetam derivatives with high nootropic activity is a promising direction in the development of new neuroprotective drugs.The aim of the study is to predict GABA-ergic and glutamatergic activities of N-acyl derivatives of 2-(2-oxopyrolidin-1-yl)- acetamide by a molecular docking method through the energy analysis of interaction of modeled structures with GABAA and AMPA receptors with their subsequent targeted synthesis.Materials and methods. The objects of the research are new N-acyl derivatives of 2-oxo-1-pyrrolidineacetamide and a virtual model of the GABAA receptor of the Homo sapiens organism with the identification code 6D6U and a three-dimensional model of the AMPA-receptor of the Rattus norvegicus organism with the identification code 3LSF from the RCSB PDB database. The simulated compounds were designed in the HyperChem 8.0.8 program. This program was also used to optimize geometry using the force field of molecular mechanics MM+. Molecular docking was carried out using the Molegro Virtual Docker 6.0.1 program. The preparation of N-acyl derivatives of 2-(2-oxopyrrolidin-1-yl)-acetamide was carried out by the interaction of 2-(2-oxopyrrolidin-1-yl)-acetamide with an excess of the corresponding anhydride under conditions of acid catalysis.Results. Based on the results of molecular docking, a high affinity of all simulated compounds for the binding site of GABAA and AMPA receptors can be estimated. According to the predict, the maximum GABA-ergic activity should be expected for (N-[2-(2-oxopyrrolidin-1-yl)-acetyl]-butyramide. N-acyl derivatives of 2-oxo-1-pyrrolidineacetamide form a more stable complex with amino acid residues Arg207, Phe200, Thr202, Tyr97, Tyr157, Tyr205 and Phe65 of the GABAA receptor binding site than the GABA molecule. In terms of the minimum interaction energy, the N-acyl derivatives of 2-(2-oxopyrrolidin-1-yl)- acetamide are superior to a number of known ligands such as GABA, piracetam, anipiracetam, picamilon and pramiracetam. The tested compounds have also shown a high affinity for the binding site of the AMPA receptor. The leader compound is also the compound PirBut, as in the case of the GABAА receptor.Conclusion. Molecular modeling of the ligands interaction with the active binding site of gamma-aminobutyric acid of the GABAA receptor by molecular docking showed that all virtual N-acyl derivatives of 2-oxo-1-pyrrolidineacetamide can exceed a number of nootropic drugs by activity. In the course of molecular design, a method for predicting a glutamatergic activity for 2-pyrrolidone derivatives has been developed. It suggests a significant nootropic activity for N-[2-(2-oxopyrrolidin-1-yl)- acetamide amides.

Novel O-[11C]methylated derivatives of candesartan as angiotensin II AT1 receptor imaging ligands: Radiosynthesis and ex vivo evaluation in rats

2009 ◽  
Vol 17 (23) ◽  
pp. 7971-7977 ◽  
Author(s):  
Tayebeh Hadizad ◽  
Sheryn A. Kirkpatrick ◽  
Samantha Mason ◽  
Kevin Burns ◽  
Rob. S. Beanlands ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Ex Vivo ◽  
At1 Receptor ◽  
Receptor Imaging ◽  
Derivatives Of
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