ORIGINAL ARTICLE
Year : 2014  |  Volume : 13  |  Issue : 1  |  Page : 1-12

Synthesis of certain N-aralkyl-N-(1-((cyclohexylamino)methyl)cyclohexyl)benzenamines and benzamides and their anticonvulsant and analgesic potential


1 Department of Medicinal and Pharmaceutical Chemistry, (Pharmaceutical Chemistry Group) Pharmaceutical and Drug Industries Research Division, Giza, Egypt
2 Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, Cairo, Egypt
3 Department of Medicinal and Pharmaceutical Chemistry (Pharmacology Group), National Research Centre, Giza, Egypt

Correspondence Address:
Mohammed N Aboul-Enein
Department of Medicinal and Pharmaceutical Chemistry, Pharmaceutical and Drug Industries Research Division, Pharm. Chem. Group, National Research Centre,12622 Dokki, Giza
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-4315.135573

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Background and objectives Epilepsy is a central nervous system disorder, affecting about 1% of the world's population, and is mostly prevalent in developing nations. In addition, many geminally disubstituted cyclohexane derivatives have proven to have anticonvulsant and analgesic activities. The aim of this study was to synthesize a new series of N-aralkyl-N-(1-((cyclohexylamino)methyl)cyclohexyl)benzenamines, 6a-h, and N-(1-((cyclohexylamino)methyl)cyclohexyl)-N-phenyl-substituted benzamides, 8a-g, for the purpose of evaluating their anticonvulsant and analgesic potential. In addition, the in-silico properties of the newly synthesized compounds have been discussed. Materials and methods Starting from 1-(N-phenylbenzamido and 4-substituted benzamido)cyclohexane carboxylic acids 3a-g, a new series of N-aralkyl-N-(1-((cyclohexylamino)methyl)cyclohexyl)benzenamines, 6a-h, was synthesized through formation of the corresponding methyl esters 4a-g, which underwent complete reduction of both the ester and the tertiary amidic carbonyl groups to afford the desired amino alcohols, 5a-g. Condensation of the corresponding mesylate esters with cyclohexylamine gave the target diamines 6a-g. Also, the alcohols 7a-g were achieved from 3a-g using NaBH 4 without affecting the amidic group, followed by preparation of the corresponding intermediate mesylate esters, which reacted with cyclohexylamine to yield the benzamidecyclohexyl amines 8a-g. The anticonvulsant and analgesic properties of 6a-h and 8a-h were studied using the pentylenetetrazole screening test and the hot-plate technique, respectively. Results and conclusion The results of the present study revealed that the most active compounds that exhibited remarkable 100% protection in mice were 6b , 6d , 6e , 8a, 8b , 8f and 8h, compared with diphenylhydantoin sodium and valproic acid, which were used as reference drugs. Both N-aralkyl-N-(1-((cyclohexyl amino)methyl)cyclohexyl)benzenamine and N-(1-((cyclohexylamino)methyl)cyclohexyl)-N-phenyl-substituted benzamide series, 6a-h and 8a-h, displayed significant antinociceptive effects. However, the 6a-h series showed higher potential than the 8a-h one. The results of the in-silico studies for the newly synthesized compounds showed that compounds 6c , 6e , 6h , 8e , 8f and 8h exhibit low mutagenic, tumorigenic, reproductive and medium irritant effect, as well as good drug-likeness and drug score.


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