Murli Dhar Kharya

Synthesis of Novel 2,5‐Disubstituted 1,3,4‐Thiadiazoles for Their Potential Anticonvulsant Activity: Pharmacophoric Model Studies

A series of novel N1‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N4‐(4‐substituted benzaldehyde)‐semicarbazone 1–12, N1‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N4‐[1‐(4‐substituted phenyl)ethanone]‐semicarbazone 13‐16, and N1‐[5‐(4‐substituted phenyl)‐1,3,4‐thiadiazol‐2‐yl]‐N4‐[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, 1H‐NMR, 13C‐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.

2,5-Disubstituted-1,3,4-oxadiazoles/thiadiazole as surface recognition moiety: Design and synthesis of novel hydroxamic acid based histone deacetylase inhibitors

The enzymatic inhibition of histone deacetylase activity has come out as a novel and effectual means for the treatment of cancer. Two novel series of 2-[5-(4-substitutedphenyl)-[1,3,4]-oxadiazol/thiadiazol-2-ylamino]-pyrimidine-5-carboxylic acid (tetrahydro-pyran-2-yloxy)-amides were designed and synthesized as novel hydroxamic acid based histone deacetylase inhibitors. The antiproliferative activities of the compounds were investigated in vitro using histone deacetylase inhibitory assay and MTT assay. The synthesized compounds were also tested for antitumor activity against Ehrlich ascites carcinoma cells in Swiss albino mice. The efforts were also made to establish structure-activity relationships among synthesized compounds. The results of the present studying indicates 2,5-disubstituted 1,3,4-oxadiazole/thiadiazole as promising surface recognition moiety for development of newer hydroxamic acid based histone deacetylase inhibitor.

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.

Novel limonene and citral based 2,5-disubstituted-1,3,4-oxadiazoles: A natural product coupled approach to semicarbazones for antiepileptic activity

Two novel series of N(4)-(5-(2/3/4-substituted-phenyl)-1,3,4-oxadiazol-2-yl)-N(1)-(2-methyl-5-(prop-1-en-2-yl)cyclohex-2-enylidene)semicarbazide and N(4)-(5-(2/3/4-substituted-phenyl)-1,3,4-oxadiazol-2-yl)-N(1)-(3,7-dimethylocta-3,6-dienylidene)-semicarbazide were synthesized to meet structural prerequisite indispensable for anticonvulsant activity. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure (MES), subcutaneous pentylenetrtrazole (scPTZ) and subcutaneous strychnine (scSTY) models. The rotorod test was conducted to evaluate neurotoxicity. Some of the selected active compounds were subjected to GABA assay to confirm their mode of action. The outcome of the present investigations proved that the four binding sites pharmacophore model is vital for anticonvulsant activity. The efforts were also made to establish structure-activity relationships among test compounds.

A novel series of 2,5-disubstituted 1,3,4-oxadiazoles: synthesis and SAR study for their anticonvulsant activity.

In search for a better anticonvulsant drug and the importance of semicarbazones and 2,5‐disubstituted 1,3,4‐oxadiazoles as anticonvulsant pharmacophore, a series of novel substituted semicarbazones were designed, synthesized, and evaluated for their anticonvulsant activity. The chemical structures of the synthesized molecules were confirmed by elemental and spectral (IR, 1H NMR, 13C NMR and MS) analysis. The anticonvulsant activities of the compounds were investigated using maximal electroshock seizure and subcutaneous pentylenetetrazole (scPTZ) models. Efforts were also made to establish structure–activity relationships among synthesized compounds. The results of the present study validated that the pharmacophore model with four binding sites is essential for anticonvulsant activity.

Synthesis and Local Anesthetic Activity of Some Novel N-[5-(4-Substituted)phenyl-1,3,4-oxadiazol-2-yl]-2-(Substituted)-Acetamides

A novel series of acetamides carrying substituted‐1,3,4‐oxadiazole moiety were synthesized from reaction of 5‐aryl‐2‐chloroacetamido‐1,3,4‐oxadiazoles with different secondary amines. The local anesthetic potential of the compounds was investigated using rabbit corneal reflex method and guinea pigs wheal derm method. The present work is the only one of its kind reporting local anesthetic activity in acetamide system combined with 1,3,4‐oxadiazole nucleus. Lidocaine was selected as standard drug in evaluation of local anesthetic activity of synthesized oxadiazole analogues. Compound 19 was found to possess significant local anesthetic activity in both the models employed for evaluation of local anesthetic activity. Compound 20, 23, 28, 29 and 35 also demonstrated marked local anesthetic activities. Structure‐activity relationships among synthesized compounds were also established.