Synthesis, molecular modeling studies, and anticonvulsant evaluation of novel 1 ‐((2‐hydroxyethyl)(aryl)amino)‐N‐substituted cycloalkanecarboxamides and their acetate esters

The 1,1 ‐disubstituted cycloalkane congeners, 1‐((2‐hydroxyethyl)(aryl)amino)‐N‐substituted cycloalkanecarboxamidesIXa –l and their acetate estersXa –l, were synthesized andin vivo tested for anticonvulsant activity. The most potent compounds in the scPTZ screen exhibited higher anticonvulsant potential than the gold standards, phenobarbital and ethosuximide. AbstractA series of 1 ‐((2‐hydroxyethyl)(aryl)amino)‐N‐substituted cycloalkanecarboxamidesIXa –l and their acetate estersXa –l were designed and synthesized as new anticovulsant agents. The evaluation of the anticonvulsant effect was performedin vivo by subcutaneous pentylenetetrazole (scPTZ) and maximal electroshock (MES) tests in mice. Further, neurotoxicity, hepatotoxicity, and acute toxicity were determined. All the new candidates displayed 100% anticonvulsant activity in the scPTZ screen in the dose range of 0.0057 –0.283 mmol/kg. The most potent compounds in the scPTZ screen wereXh (ED50 = 0.0012 mmol/kg),Xd (ED50 = 0.002 mmol/kg),Xf (ED50 = 0.004 mmol/kg),IXj (ED50 = 0.0047 mmol/kg),Xl (ED50 = 0.0076 mmol/kg), andXi (ED50 = 0.008 mmol/kg). They exhibited higher fold activity in the anticonvulsant potential than the gold standards, phenobarbital and ethosuximide. CompoundXf was active in both scPTZ and MES screens. It showed ED50 of 0.016  mmol/kg in MES screen. In the neurotoxicity screens, none of the test compounds displayed any minimal motor im...

Source: Archiv der Pharmazie - November 21, 2018 Category: Drugs & Pharmacology Authors: Mohamed N. Aboul ‐Enein, Aida A. El‐Azzouny, Kamilia M. Amin, Mona E. Aboutabl, Mai I. Abo‐Elmagd Tags: FULL PAPER Source Type: research