Synthesis of novel 2,5-disubstituted 1,3,4-thiadiazoles for their potential anticonvulsant activity: pharmacophoric model studies.
A series of novel N(1)-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N(4)-(4-substituted benzaldehyde)-semicarbazone 1-12, N(1)-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N(4)-[1-(4-substituted phenyl)ethanone]-semicarbazone 13-16, and N(1)-[5-(4-substituted phenyl)-1,3,4-thiadiazol-2-yl]-N(4)-[1-(4-substituted phenyl) (phenyl) methanone]-semicarbazone 17-20 were synthesized for their anticonvulsant activity. The chemical structures of the compounds were proved by elemental and spectral (IR, (1)H-NMR,( 13)C-NMR, and MS) analysis. The anticonvulsant potential of the compounds was investigated using maximal electroshock seizure (MES) and subcutaneous pentylenetrtrazole (scPTZ) models. Compound 19 was found to possess significant anticonvulsant activity in both the models employed for anticonvulsant evaluation. Compounds 8, 13, 15, and 16 also demonstrated a marked anticonvulsant property. The results of the present study validated that the pharmacophore model with four binding sites is essential for anticonvulsant activity. The efforts were also made to establish structure-activity relationships among the synthesized compounds.
Rajak
Harish
H
Medicinal Chemistry Division, SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur, (CG), India. harishdops@yahoo.co.in
Deshmukh
Ravitas
R
Aggarwal
Navneet
N
Kashaw
Sushil
S
Kharya
Murli Dhar
MD
Mishra
Pradeep
P
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000627:therapeutic use; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D004597:Electroshock; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010433:Pentylenetetrazole; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D012664:Semicarbazones / Q000737:chemistry; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis* / Q000627:therapeutic use*
D000927:Anticonvulsants; D012664:Semicarbazones; D013830:Thiadiazoles; D010433:Pentylenetetrazole