One of the important core fragments of anticonvulsants is defined by a nitrogen heteroatomic system, usually a cyclic imide, at least of one carbonyl group and phenyl or alkyl groups attached to the heterocyclic system [1]. It was confirmed in our previous studies which have demonstrated the potent anticonvulsant activity among several classes of succinimides. Following these results, as part of our efforts to design new anticonvulsant agents in the present study we have synthesized a library of 60 compounds with N-phenylamino pyrrolidine-2,5-dione system as a core fragment and different substituents at the position-3 of imide ring (Fig. 1).

Fig. 1.

The initial pharmacological studies were performed within the Antiepileptic Drug Development (ADD) Program in Epilepsy Branch, National Institutes of Health, National Institute of Neurological Disorders and Stroke (NIH/NINDS), Bethesda, MD, USA [2]. The results obtained revealed that majority of compounds investigated showed potent anticonvulsant activity in the animal models of epilepsy. It is noteworthy that several of these molecules revealed protection comparable with the marked AEDs. The results obtained enabled the extensive SAR discussion, which showed that the activity depended mainly on the substitution mode at the position-3 of succinimide as well as the kind of substituents at the phenyl ring.

References

[1] M.G. Wong, J.A. Defina, P.R. Andrews, J. Med. Chem. 1986, 29, 562-572.
[2] H.J. Kupferberg, Epilepsia 1989, 30 (Suppl.), 51-56.

• Legal notice:
  

  Copyright (c) Pielaszek Research, all rights reserved.
  The above materials, including auxiliary resources, are subject to Publisher's copyright and the Author(s) intellectual rights. Without limiting Author(s) rights under respective Copyright Transfer Agreement, no part of the above documents may be reproduced without the express written permission of Pielaszek Research, the Publisher. Express permission from the Author(s) is required to use the above materials for academic purposes, such as lectures or scientific presentations.
  In every case, proper references including Author(s) name(s) and URL of this webpage: https://science24.com/paper/14713 must be provided.

1. Design, synthesis and anticonvulsant activity of new N-Mannich bases derived from 3-phenylpyrrolidine-  2,5-diones
2. Synthesis, anticonvulsant activity and 5-HT_1A/5-HT₇ receptors affinity of new 1-[(4-substituted-  piperazin-1-yl)-alkyl]- 3-methyl- 3-(2-methylpropyl)-pyrrolidine- 2,5-diones
3. Synthesis and anticonvulsant activity of new 5-(cyclo)alkyl-5-phenyl-imidazolidine-2,4-diones derivatives with arylpiperazinylpropyl moiety
4. Synthesis and anticonvulsant activity of new N-Mannich bases derived from 5-cyclopropyl-5-(4-chlorophenyl)- imidazolidine-2,4-diones
5. Synthesis and anticonvulsant activity of N-substituted 8-azaspiro[4.5]decane-7,9-diones, 3-azaspiro[5.5]unde-cane-2,4-diones and 4-ethyl-4-methylpiperidine- 2,6-diones
6. Synthesis and anticonvulsant activity of new N-[4-(arylpiperazin 1-yl)]- 1,3-dioxo-1,3-dihydro-2H- isoindole- and 1,3-dioxooctahydro-2H-isoindole-2-carboxa- mides
7. Synthesis and anticonvulsant activity of new N-[(4-arylpiperazin-1-yl)-methyl]- 3-phenyl-pyrrolidine-2,5-dione derivatives
8. SYNTHESIS, PHYSICOCHEMICAL AND ANTICONVULSANT PROPERTIES OF NEW N-AMINOPHENYL AZASPIRANE AND PYRROLIDINE-2,5-DIONE DERIVATIVES
9. SYNTHESIS AND ANTICONVULSANT ACTIVITY OF NOVEL N-PYRIDINE-2-YL AND N-AMINOPHENYL DERIVATIVES OF 3,3-DIALKYL-PYRROLIDINE-2,5-DIONES
10. ANTICONVULSANT PROPERTIES AND 5-HT_1A, 5-HT_2A RECEPTOR AFFINITY OF NEW N-[(4-ARYLPIPERAZIN-1-YL)-ALKYL] - 2 - AZASPIRO[4.4]NONANE- AND [4.5]DECANE-1,3-DIONES
11. NEW ARYLPIPERAZINE DERIVATIVES OF 3-PHENYLPYRROLIDINE-2,5-DIONE AS POTENTIAL ANTICONVULSANT AGENTS