Synthesis, Molecular Modeling, Anticonvulsant and Antinociceptive Properties of New 1,1‐Disubstituted Cyclohexane and 1,3‐Diazaspiro[4.5]decane Derivatives

The current work describes the synthesis of new series of N‐(1‐(cyclohexylcarbamoyl) cyclohexyl)‐N‐phenylarylamides ( 10 a‐h ) and 3‐cyclohexyl‐1,2‐diphenyl and 2‐(substituted phenyl)‐1,3‐diazaspiro[4.5]decanes ( 12 a‐h ).The new compounds were screened for their anticonvulsant and antinociceptive activities using sodium valproate and tramadol hydrochloride, respectively as reference standards. 4‐Chloro‐N‐(1‐(cyclohexylcarbamoyl)cyclohexyl)‐N‐phenylbenzamide ( 10 b) , 3‐Cyclohexyl‐1,2‐diphenyl‐1,3‐diazaspiro[4.5]decane (12 a) and 3‐Cyclohexyl‐1‐phenyl‐2‐(3,4,5‐trimethoxyphenyl)‐1,3‐diazaspiro[4.5]decane (12 d) showed higher anticonvulsant activity than sodium valproate at dose 0.08 mmol/kg. On the other hand, 4‐Amino‐N‐(1‐(cyclohexylcarbamoyl) cyclohexyl)‐N‐phenylbenzamide (10 h) and 3‐Cyclohexyl‐1‐phenyl‐2‐(3,4,5‐trimethoxyphenyl)‐1,3‐diazaspiro[4.5]decane (12 d) exhibited higher antinociceptive potential in both intensity and duration than tramadol hydrochloride. The pharmacokinetics of the new compounds were calculated in‐ silico . Additionally, 3D pharmacophoric model was generated.