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Synthesis, Molecular Modeling, Anticonvulsant and Antinociceptive Properties of New 1,1‐Disubstituted Cyclohexane and 1,3‐Diazaspiro[4.5]decane Derivatives
Author(s) -
AboulEnein Mohamed Nabil,
ElAzzouny Aida A.,
Ragab Fatma,
AbdelMaksoud Mohammed S.,
AbdAllah Walaa H.,
Maklad Yousreya
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201803727
Subject(s) - chemistry , decane , hydrochloride , cyclohexane , diclofenac sodium , anticonvulsant , stereochemistry , medicinal chemistry , organic chemistry , chromatography , epilepsy , medicine , psychiatry
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.