A series of new dicyano-containing dibenzo[b,f]imidazo[1,2-d][1,4]oxazepines was synthesized in 25–90
A solution to the thermoelastic problem in a thin layer on a curvilinear cylindrical surface is proposed. Generality of the problem and its solution are achieved by selecting a coordinate system maximally adapted to the surface profile. The general integration of the two-dimensional Laplace thermal equation is performed with respect to a specific thermal coordinate. The system of thermoelastic equations for the layer is integrated assuming that its thickness is small compared to the surface radius of curvature. Based on the general conditions for the extremum of the von Mises criterion, material failure criteria at the outer and inner boundaries of the layer are determined. The proposed method can be used to predict the durability of thermal barrier coatings for gas turbine engine blades.
Novel cyano-containing 6H,14H-6,14-methanobenzo[g]benzo[4,5]thiazolo[2,3-d][1,3,5]-oxadiazocines were synthesized with a yield of up to 58
INTRODUCTION:Phenibut, a GABAB receptor agonist, is used for anxiety and insomnia but is limited by side effects like drowsiness and withdrawal symptoms. This study aimed to identify a novel GABAB receptor modulator with improved efficacy and safety. METHODS:A drug database of 15,000 compounds was screened using the Tanimoto similarity coefficient, identifying three candidates. Molecular docking and dynamics simulations assessed their binding affinity and stability with the GABAB receptor. The lead compound, 3-[(2-oxo-2- phenylethyl)amino]benzoic acid (C1), was tested in vivo using a stress-induced Wistar rat model (n=20, male, 200-250 g), with phenibut as a reference. Anxiety-like behaviour was evaluated via the elevated plus maze, and pharmacokinetic properties were analyzed. RESULTS:C1 exhibited superior binding affinity (ΔGbind = -8.5 kcal/mol) and stability compared to phenibut (-8.0 kcal/mol). In vivo, C1 significantly increased open-arm time (110.80 ± 26.10 min) compared to phenibut (57.80 ± 9.40 min, p<0.05), indicating reduced anxiety-like behaviour. C1 also showed favourable oral bioavailability and blood-brain barrier permeability. DISCUSSION:Consistently, C1 demonstrated superior performance compared to phenibut, suggesting its potential as a more effective alternative for GABAB receptor modulation. CONCLUSION:C1 is a promising alternative to phenibut, demonstrating enhanced anxiolytic effects and a favourable safety profile. Further studies are warranted to confirm its clinical potential.
