Ethosuximide is a succinimide anticonvulsant active pharmaceutical ingredient. A simple static method by determining the cloud point pressure is employed to measure the solubility of ethosuximide in supercritical carbon dioxide (SC-CO 2 ) at various temperatures T /K = (313.15, 318.15, 323.15 and 328.15) and in pressures P/ MPa = (9–15). The experimental solubility of ethosuximide in SC-CO 2 is found to be between 3.45E-03 and 8.71E-03 in terms of mole fraction under the experimental conditions. The measured solubility data are successfully correlated by four semi-empirical models including Chrastil, Bartle et al., Kumar and Johnston (K-J) and Mendez-Santiago-Teja (MST). The correlation results show good agreement with the experimental data. The average absolute relative deviation (AARD) between the measured values and the calculated ones are 2.64%, 2.98%, 3.02% and 3.25% for Chrastil, Bartle, K-J and MST respectively. The results of this study provide the effective fundamental for the probable processes based on SC-CO 2 .
A novel molecularly imprinted electrochemiluminescene (ECL) sensor was fabricated for the detection of ethosuximide . The new Ru(pby) 3 2+ @N-GQDs (tris(2,2′-bipyridyl) ruthenium(II)@nitrogen doped graphene quantum dots) nanocomposite was synthesized by electrostatic interaction between Ru(pby) 3 2+ and N-GQDs, which showed excellent and stable ECL properties. And then dopamine as functional monomer and ethosuximide as template molecule were co -polymerized by hydrogen bonding on the surface of Ru(pby) 3 2+ @N-GQDs/Nafion. After ethosuximide was extracted with H 2 SO 4 , the molecularly imprinted cavities in film were formed. When ethosuximide rebound onto imprinted cavities again, the ECL intensity of Ru(pby) 3 2+ @N-GQDs decreased. Based on this principle, the quantitative relationship between the concentration of ethosuximide ( c ) and the variation of ECL intensity (Δ I ECL ) was established. Namely the Δ I ECL depended linearly on the log c in the range from 5.00 × 10 −7 to 1.00 × 10 −4 mol/L with a detection limit of 3.00 × 10 −7 mol/L (S/N = 3), and the correlation coefficient was 0.9984. The proposed sensor was also applied in plasma and urine samples with recovery in range from 97.80% to 106.2% (RSD < 6.3%).
Mengjiao Li,Lina Hu,Shijia Yi,Hui Yan,Zheng Liu,Kang Lei,Xuekun Wang,Shiben Wang
In this paper, two series of triazolopyrimidines derivatives were designed, synthesized, and all the target compounds were structurally confirmed using 1 H NMR, 13 C NMR and HRMS methods. Pharmacological experiments were carried out using maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ) and rotating rod (ROT) models for activity and neurotoxicity screening, and potential compounds were screened out for further determination of ED 50 , TD 50 and in vitro binding experiments. Finally, compound 5,7-Bis(pentyloxy)-[1,2,4]triazolo[1,5-a]pyrimidine ( 6b ) with best activity and lowest toxicity was obtained. The pharmacological results showed that the ED 50 of compound 6b was MES = 11.3 mg/kg, PTZ = 9.5 mg/kg, which was superior to that of the carbamazepine (MES = 6.3 mg/kg) and ethosuximide (PTZ = 3.6 mg/kg). The IC 50 of compound 6b binding affinity toward the GABA A receptor was 0.15 µM, and the GABA content experiments showed that compound 6b significantly increased the GABA content in the rat brain. In elevated plus maze (EPM) assay, compound 6b possessed anxiolytic effects. In silico studies, most of the target compounds have suitable physicochemical and pharmacokinetic data with the possibility of drug-forming properties, molecular docking results showed that compound 6b could generate more interactions with the amino acid residues of diazepam active site of GABA A receptor.
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