- Design and synthesis of novel potent antinociceptive agents: Methyl-imidazolyl N-acylhydrazone derivatives
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This paper describes recent results of design, synthesis and pharmacological evaluation of new N-heterocyclic functionalized N-acylhydrazone compounds, belonging to the 2-methyl-imidazolyl-3-acylhydrazone class (4a-e). These compounds were planned by applying the molecular simplification strategy to propose the structural modifications on the previously described functionalized imidazo[1,2-a]pyridine 3-acylhydrazone series (2), which presented an important analgesic profile. This new series (4) was synthesized in order to investigate the possible pharmacophoric contribution of the N-heteroaromatic ring and N-acylhydrazone moieties to the analgesic activity. Compounds 4a-b are the most potent antinociceptive agents from this series. Copyright (C) 2000 Elsevier Science Ltd.
- Figueiredo, Juliana M.,Camara, Celso De A.,Amarante, Emanuel G.,Miranda, Ana Luisa P.,Santos, Fulvia M.,Rodrigues, Carlos R.,Fraga, Carlos Alberto M.,Barreiro, Eliezer J.
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p. 2243 - 2248
(2007/10/03)
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- New synthetic routes to pyrrolo-[1,2-a]- and -[1,2-c]-imidazol-5-ones by flash vacuum pyrolysis
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1-Substituted and 1,3-disubstituted pyrrolo[1,2-c]imidazol-5-ones 25-27 have been made in fair to excellent yield by flash vacuum pyrolysis (FVP) of the Meldrum's acid precursors 11-13. FVP of the appropriate propenoate precursor 23, 22 and 18-20 gives pyrrolo[1,2-c]imidazol-5-one 2, pyrrolo[1,2-a]-imidazol-5-one 3 and their 6-methyl derivatives 28-30 respectively in 32-90% yield. The mechanism of the propenoate pyrolyses involves rate determining E to Z isomerisation of the alkene followed by elimination of an alcohol and electrocyclisation to the fused ring products.
- McNab, Hamish,Thornley, Craig
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p. 2203 - 2209
(2007/10/03)
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- Synthesis of 4(5)-Acyl-, 1-Substituted 5-Acyl, and 1-Substituted 4-Acyl-1H-imidazoles from 4-Aminoisoxazoles
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4-Aminoisoxazoles can be acylated with a wide variety of activated carboxylic acids.Hydrogenation of the resulting amides gives α-(acylamino)enaminones, which cyclize to 4(5)-acylimidazoles upon treatment with base.This method allows for the synthesis of acylimidazoles with a wide range of substituents at C-2.Utilization of N-substituted 4-aminoisoxazoles in the same sequence of reactions yields 1-substituted 5-acylimidazoles, a substitution pattern not otherwise easily prepared.Treatment of α-(acylamino)enaminones, derived from N-unsubstituted isoxazoles, with primary amines leads to incorporation of the amine at the β-position with concomitant expulsion of ammonia.This sequence efficiently yields 1-substituted and 1,2-disubstituted 4-acylimidazoles but does not give satisfactory yields of 5-substituted 4-acylimidazoles due to steric inhibition of the amine exchange.
- Reiter, Lawrence A.
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p. 2714 - 2726
(2007/10/02)
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