Dipropofol

Abstract: A simple procedure for obtaining previously unknown diphthalonitriles based on 4-nitrophthalonitrile and 3,3′,5,5′-tetrasubstituted biphenyl-4,4′-diol derivatives in a binary solvent system DMF-water was developed.The possibilities and limitations of using 3,3′,5,5′-tetrasubstituted biphenyl-2,2′-diol derivatives as reagents for the synthesis of diphthalonitriles and corresponding dianhydrides were demonstrated.The effect of the substrate nature on the yield of target diphthalonitriles was considered using 2,2′,3,3′,5,5′-hexamethylbiphenyl-4,4′-diol as an example.

Temporal lobe epilepsy (TLE), the most common pharmacoresistant focal epilepsy disorder, remains a major unmet medical need. Propofol is used as a short-acting medication for general anesthesia and refractory status epilepticus with issues of decreased consciousness and memory loss. Dipropofol, a derivative of propofol, has been reported to exert antioxidative and antibacterial activities. Here we report that dipropofol exerted anticonvulsant activity in a mouse model of kainic acid-induced seizures. Whole cell patch-clamp recordings of brain slices from the medial entorhinal cortex (mEC) revealed that dipropofol hyperpolarized the resting membrane potential and reduced the number of action potential firings, resulting in suppression of cortical neuronal excitability. Furthermore, dipropofol activated native tonic GABAAcurrents of mEC layer II stellate neurons in a dose-dependent manner with an EC50value of 9.3 ± 1.6 μM (mean ± SE). Taken together, our findings show that dipropofol activated GABAAcurrents and exerted anticonvulsant activities in mice, thus possessing developmental potential for new anticonvulsant therapy.NEW & NOTEWORTHY The anticonvulsant effect of dipropofol was shown in a mouse model of kainic acid-induced seizures. Whole cell patch-clamp recordings of brain slices showed suppression of cortical neuronal excitability by dipropofol. Dipropofol activated the native tonic GABAAcurrents in a dose-dependent manner.