Syntheses and evaluation of anticonvulsant activity of novel branched alkyl carbamates.
In: Journal of medicinal chemistry, Jg. 55 (2012-03-22), Heft 6, S. 2835-45
academicJournal
Zugriff:
A novel class of 19 carbamates was synthesized, and their anticonvulsant activity was comparatively evaluated in the rat maximal electroshock (MES) and subcutaneous metrazol (scMet) seizure tests and pilocarpine-induced status epilepticus (SE) model. In spite of the alkyl-carbamates' close structural features, only compounds 34, 38, and 40 were active at the MES test. The analogues 2-ethyl-3-methyl-butyl-carbamate (34) and 2-ethyl-3-methyl-pentyl-carbamate (38) also exhibited potent activity in the pilocarpine-SE model 30 min postseizure onset. Extending the aliphatic side chains of homologous carbamates from 7 to 8 (34 to 35) and from 8 to 9 carbons in the homologues 38 and 43 decreased the activity in the pilocarpine-SE model from ED(50) = 81 mg/kg (34) to 94 mg/kg (35) and from 96 mg/kg (38) to 114 mg/kg (43), respectively. The most potent carbamate, phenyl-ethyl-carbamate (47) (MES ED(50) = 16 mg/kg) contains an aromatic moiety in its structure. Compounds 34, 38, 40, and 47 offer the optimal efficacy-safety profile and, consequently, are promising candidates for development as new antiepileptics.
Titel: |
Syntheses and evaluation of anticonvulsant activity of novel branched alkyl carbamates.
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Autor/in / Beteiligte Person: | Hen, N ; Bialer, M ; Yagen, B |
Zeitschrift: | Journal of medicinal chemistry, Jg. 55 (2012-03-22), Heft 6, S. 2835-45 |
Veröffentlichung: | Washington Dc : American Chemical Society ; <i>Original Publication</i>: [Easton, Pa.] : American Chemical Society, [c1963-, 2012 |
Medientyp: | academicJournal |
ISSN: | 1520-4804 (electronic) |
DOI: | 10.1021/jm201751x |
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