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Synthesis of Novel 2,5‐Disubstituted 1,3,4‐Thiadiazoles for Their Potential Anticonvulsant Activity: Pharmacophoric Model Studies
Author(s) -
Rajak Harish,
Deshmukh Ravitas,
Aggarwal Navneet,
Kashaw Sushil,
Kharya Murli Dhar,
Mishra Pradeep
Publication year - 2009
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.200800213
Subject(s) - semicarbazone , chemistry , anticonvulsant , pharmacophore , thiadiazoles , stereochemistry , proton nmr , benzaldehyde , medicinal chemistry , organic chemistry , epilepsy , neuroscience , biology , catalysis
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.