Continued efforts are being in the development of antiepileptic drugs employing a range of strategies, including modification of the structures of existing drugs, targeting novel molecular substrate and non-mechanism-based drug screening of compounds in animal models. To make the discovery of new anticonvulsants more rational many investigators identified structural fragments essential for anticonvulsant properties. One of the important core fragments of anticonvulsants is defined by a nitrogen heteroatomic system usually a cyclic imide, at least of one or two carbonyl groups and phenyl or alkyl substituents attached to the heterocyclic system.^1,2 The previous studies from our laboratory have demonstrated potent anticonvulsant activity in groups of N-benzyl-, N-phenyl-, N-phenylamino-, N-pyrid-2-yl- spirossuccinimides and 3,3-dialkyl-pyrro-lidine-2,5- diones.^3-6 These molecules were effective in electrically induced seizures (MES) or/and in the subcutaneous pentylenetetrazole screen (scPTZ) which are recognized as the “gold standards” in the early stages of testing. As a continuation of our systematic SAR analysis in the present studies we have obtained a small library of N-substituted spiroglutarimides and 4-ethyl-4-methyl- piperidine-2,6-diones which were designed as analogues of the most active succinimides (Figure 1). Such modification enable the examination of influence of the heterocyclic ring size on the anticonvulsant activity.

Figure 1.

The desired compounds were prepared by cyclocondensation reaction of 8-oxaspiro[4.5]decane-7,9-dione, 3-oxaspiro- [5.5]undecane- 2,4-dione or 3-ethyl-3-methyl-glutaric acid with the respective amines. The compounds were evaluated for their anticonvulsant activity and neurotoxic properties within the Antiepileptic Drug Development (ADD) Program (Epilepsy Branch, Neurological Disorders Program, National Institute of the Neurological and Communicative Disorders and Stroke (NINCDS), Rockville, USA).⁷

References:

¹ Estrada E., Pena A. Bioorg. Med. Chem. 2000, 8, 2755. ² Wong M.G., Defina J.A., Andrews P.R. J. Med. Chem. 1986, 29, 562. ³ Kamiński K., Obniska J. Bioorg. Med. Chem. 2008, 16, 4921. ⁴ Kamiński K., Obniska J., Dybała M. Eur. J. Med. Chem. 2008, 43, 53.

• 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/22951 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. The multiobjective based design, synthesis and evaluation of the arylsulfonamide/amide derivatives of arylxyethyl- and arylthioethyl- piperidines and pyrrolidines as a novel class of potent 5-HT₇ receptor antagonists
5. Induced Fit Homology Model of the 5-HT₆ Serotonin Receptor - Application for Virtual Screening
6. Synthesis and anticonvulsant activity of new N-Mannich bases derived from 5-cyclopropyl-5-(4-chlorophenyl)- imidazolidine-2,4-diones
7. 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
8. N-Phenylamino derivatives of 3-substituted pyrrolidine-2,5-diones as potential anticonvulsant agents
9. Synthesis and anticonvulsant activity of new N-[(4-arylpiperazin-1-yl)-methyl]- 3-phenyl-pyrrolidine-2,5-dione derivatives
10. SYNTHESIS, PHYSICOCHEMICAL AND ANTICONVULSANT PROPERTIES OF NEW N-AMINOPHENYL AZASPIRANE AND PYRROLIDINE-2,5-DIONE DERIVATIVES
11. SYNTHESIS AND ANTICONVULSANT ACTIVITY OF NOVEL N-PYRIDINE-2-YL AND N-AMINOPHENYL DERIVATIVES OF 3,3-DIALKYL-PYRROLIDINE-2,5-DIONES
12. 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
13. NEW ARYLPIPERAZINE DERIVATIVES OF 3-PHENYLPYRROLIDINE-2,5-DIONE AS POTENTIAL ANTICONVULSANT AGENTS