Synthesis and Biological Evaluation of Chiral -Aminoanilides with Central Antinociceptive Activity
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- 作者：Filomena Corbo ; Carlo Franchini ; Giovanni Lentini ; Marilena Muraglia ; Carla Ghelardini ; Rosanna Matucci ; Nicoletta Galeotti ; Elisa Vivoli ; Vincenzo Tortorella
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：April 19, 2007
- 年：2007
- 卷：50
- 期：8
- 页码：1907 - 1915
- 全文大小：153K
- 年卷期：v.50,no.8(April 19, 2007)
- ISSN：1520-4804
文摘
Tocainide and related optically active chiral 
-aminoanilides were synthesized and tested in vivo via thehot plate test to evaluate their central analgesic action. The aims of the study were to verify if a) the increasein lipophilicity, obtained by the introduction of an alkyl group on the steric center (3f-i), and the replacementof the C=O group with the C=S (10) group as well as the introduction of a methyl or ethyl group on theamidic nitrogen atom (8a-c) would produce an increase in central analgesic efficacy with respect to Tocainide;b) the 2,6-xylidide moiety is crucial for high analgesic activity (3b-e); c) the hydrogen atom bonded to theamidic nitrogen moiety is an essential pharmacophoric element for analgesic activity. Among all thesynthesized compounds, 3f showed antinociceptive properties with a good enantioselective index.
-aminoanilides were synthesized and tested in vivo via thehot plate test to evaluate their central analgesic action. The aims of the study were to verify if a) the increasein lipophilicity, obtained by the introduction of an alkyl group on the steric center (3f-i), and the replacementof the C=O group with the C=S (10) group as well as the introduction of a methyl or ethyl group on theamidic nitrogen atom (8a-c) would produce an increase in central analgesic efficacy with respect to Tocainide;b) the 2,6-xylidide moiety is crucial for high analgesic activity (3b-e); c) the hydrogen atom bonded to theamidic nitrogen moiety is an essential pharmacophoric element for analgesic activity. Among all thesynthesized compounds, 3f showed antinociceptive properties with a good enantioselective index.