Potent Anticonvulsant 1H-Imidazol-5(4H)-One Derivatives with Low Neurotoxicity

Abstract

We report here the synthesis and in vivo anticonvulsant/neurotoxicity activities of a series of compounds belonging to 2-aryl-4-arylidene-1-phenyl-1H-imidazol-5(4H)-one. The scaffold is based on the commonality of 5-membered lactam ring structures as successful anticonvulsant agents. The present compounds exhibited a range of anticonvulsant activity in pentylenetetrazole (PTZ)-induced seizure test. In particular, the protection was excellent by compounds bearing furylmethylidene on C4, possibly due to good pharmacokinetic properties. It was found that high lipophilicity and/or electron deficient aryl ring substitution at C4 compromised the anticonvulsant activities. For example, chloro analogues were found much less active than unsubstituted phenyl or furyl derivatives. Regarding side effects, active compounds exerted no observable neurotoxic effect at their therapeutic doses in Chimney test.

Design, Synthesis and Antiproliferative Activities of Oxidative Stress Inducers Based on 2-Styryl-3,5-dihydro-4<i>H</i>-imidazol-4-one Scaffold

“…Our observation of cleaved caspase 3 over expression and nuclear translocation after treatment by 3a and 3e within HCT116 cell offered another evidence of apoptosis induction via ROS generation. Cleaved caspase 3 induction of cell death is consistent with studies on tCA, BCA 21,23) (Fig. 1).…”

“…18,19) On the downside, tCA is an aldehyde with a high metabolic conversion rate and poor pharmacokinetics and it is not suitable for drug development. 20,21) In this report, we aimed to synthesize and investigate cytotoxic properties of 2-styryl-4-imidazolone series of compounds incorporating the styryl portion of the tCA.…”

Antiproliferative Properties of Vinyl Dipeptides: Synthesis and MCF-7 Cell Line Testing

“…lenmeyer conditions [13]. The lactone intermediate 3 was heated with a set of different aliphatic, aromatic and heterocyclic amines under microwave conditions in N, Ndimethylformamide (DMF) to give the vinylamide titled compounds except the 4-aminophenol that underwent dehydration and ring closure, under the same experimental conditions, giving the 5(4H)-imidazolone 4.…”