Synthesis and Anticonvulsant Activity of N‐(2‐Hydroxy‐ethyl)amide Derivatives

Abstract

A series novel of N-(2-hydroxyethyl)amide derivatives was synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test, and their neurotoxicity was evaluated by the rotarod test (Tox). The maximal electroshock test showed that N-(2-hydroxyethyl)decanamide 1g, N-(2-hydroxyethyl)palmitamide 1l, and N-(2-hydroxyeth-yl)stearamide 1n were found to show a better anticonvulsant activity and also had lower toxicity than the marked anti-epileptic drug valproate. In the anti-MES potency test, these compounds exhibited median effective doses (ED50) of 22.0, 23.3, 20.5 mg/kg, respectively, and median toxicity doses (TD50) of 599.8, >1000, >1000 mg/kg, respectively, resulting in a protective index (PI) of 27.5, >42.9, >48.8, respectively. This is a much better protective index than that of the marked anti-epileptic drug valproate (PI = 1.6). To further investigate the effects of the anticonvulsant activity in several different models, compounds 1g, 1l, and 1n were tested having evoked convulsions with chemical substances, including pentylenetetrazloe, isoniazide, 3-mercaptopropionic acid, bicuculline, thiosemicarbazide, and strychnine.

Different roles for the acyl chain and the amine leaving group in the substrate selectivity of N-Acylethanolamine acid amidase

“…: 285.27, found: (t, 2H, J ¼ 7.4 Hz), 1.63 (pent, 2H, J ¼ 7.5 Hz), 1.40-1.13 (m, 22H), 0.88 (t, 3H, J ¼ 6.9 Hz). Analytical data are consistent with those previously reported in the literature 45 .…”

“…1 H-NMR (400 MHz, Chloroform-d): d 5.96 (br, 1H), 3.72 (q, 2H, J ¼ 4.8 Hz), 3.42 (q, 2H, J ¼ 5.4 Hz), 2.75 (t, 1H, J ¼ 5.1 Hz), 2.20 (t, 2H, J ¼ 7.6 Hz), 1.63 (pent, 2H, J ¼ 7.6 Hz), 1.40-1.11 (m, 26H), 0.88 (t, 3H, J ¼ 7.0 Hz). Analytical data are consistent with those previously reported in the literature45 .Synthesis of N-(2-hydroxyethyl)octadecanamide (compound 6)Procedure A, octadecanoyl chloride (0.49 g), ethanolamine (0.21 mL), yield ¼ 519 mg (98%) . MS calc.…”

Current Research on Antiepileptic Compounds

“…In the anti-MES potency test, these compounds exhibited ED 50 doses of 22.0, 23.3, 20.5 mg/kg, respectively, and TD 50 doses of 599.8, >1000, >1000 mg/kg, respectively, resulting in a PI of 27.5, >42.9, >48.8, respectively, which are much higher than valproate (PI = 1.6) [181].…”

Fatty Acid Amides Synthesized from Andiroba Oil (Carapa guianensis Aublet.) Exhibit Anticonvulsant Action with Modulation on GABA-A Receptor in Mice: A Putative Therapeutic Option

“…The determination of the FAA dose was based on previous literature [78] and a dose-response curve using linear regression based on the increase in latency of tonic-clonic seizures. The determination of the PTZ dose has been reported before [79].…”