title: Synthesis of novel 2,5-disubstituted 1,3,4-thiadiazoles for their potential anticonvulsant activity: pharmacophoric model studies.
abstract: 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.
authors: Medicinal Chemistry Division, SLT Institute of Pharmaceutical Sciences, Guru Ghasidas University, Bilaspur, (CG), India. harishdops@yahoo.co.in
authors: Harish
authors: H
authors: Rajak
authors: Ravitas
authors: R
authors: Deshmukh
authors: Navneet
authors: N
authors: Aggarwal
authors: Sushil
authors: S
authors: Kashaw
authors: Murli Dhar
authors: MD
authors: Kharya
authors: Pradeep
authors: P
authors: Mishra
mesh_terms: 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*
chemical_list: D000927:Anticonvulsants; D012664:Semicarbazones; D013830:Thiadiazoles; D010433:Pentylenetetrazole