Novel semicarbazones based 2,5-disubstituted-1,3,4-oxadiazoles: one more step towards establishing four binding site pharmacophoric model hypothesis for anticonvulsant activity.
A series of novel N(1)-{5-[(naphthalene-2-yloxy)methyl]-1,3,4-oxadiazol-2-yl}-N(4)-(4-substitutedbenzaldehyde)-semicarbazone, N(1)-{5-[(naphthalene-2-yloxy)methyl]-1,3,4-oxadiazol-2-yl}-N(4)-[1-(4-substitutedphenyl)ethanone]-semicarbazone and N(1)-{5-[(naphthalene-2-yloxy)methyl]-1,3,4-oxadiazol-2-yl}-N(4)-[1-(4-substitutedphenyl) (phenyl) methanone]-semicarbazone were designed and synthesized on the basis of semicarbazone based pharmacophoric model to meet the structural requirements necessary for anticonvulsant activity. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES), subcutaneous pentylenetrtrazole (scPTZ) and subcutaneous strychnine (scSTY) models. Some of the selected active compounds were subjected to GABA assay to confirm their mode of action. The efforts were also made to establish structure activity relationships among synthesized compounds. The results of the present studying validated that the pharmacophoric model with four binding sites is essential for anticonvulsant activity.
Rajak
Harish
H
Medicinal Chemistry Research Laboratory, SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur 495 009, CG, India. harishdops@yahoo.co.in
Deshmukh
Ravitas
R
Veerasamy
Ravichandran
R
Sharma
Ajay Kumar
AK
Mishra
Pradeep
P
Kharya
Murli Dhar
MD
D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D008958:Models, Molecular; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D012664:Semicarbazones / Q000737:chemistry* / Q000494:pharmacology
D000927:Anticonvulsants; D010069:Oxadiazoles; D012664:Semicarbazones