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Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES This work reports the results of the reactivity study of the ethyl cyano-acrylates (3), obtained from the Horner-Wadsworth-Emmons (HWE) olefination reaction applied to α,β-unsaturated ketones (1) with diethyl (cyanomethyl)phosphonate (2). Eight examples of 6-aryl-4-ethoxycarbonyl-2H-pyran-2-ones (4) were synthesized by the autocondensation reaction of ethyl 4-aryl-2-(cyanomethylene)-4-methoxy-but-3-enoates (3), under reflux of water in the presence of hydrochloric acid, furnishing the products with yields from 15% to 66%. An unprecedented series of six 7-akyl-5-cyanomethyl-3,4,7,7a-tetrahydropyrano[2,3-b]pyrrol-6(2H)-ones (6) was synthesized by the reaction of ethyl 3-cyano-2-(3,4-dihydro-2H-pyran-5-yl)acrylate (3) with primary amines (5), without catalysts in a solvent-free condition, giving yields from 55% to 75%. It was observed that the ethyl 2-(4,5-dihydrofuran-3-yl)-2-oxoacetate (1j) undergoes a spontaneous rearrangement with the formation of ethyl 3-formyl-4,5-dihydrofuran-2-carboxylate (7). Subsequently, it was studied the ideal conditions for the controlled conversion of compound 1j to 7. The unprecedented compound 7 was submitted to the olefination reaction with diethyl (cyanomethyl)phosphonate, which afforded ethyl 3-(2-cyanovinyl)-4,5-dihydrofuran-2-carboxylate (8). The reactivity of compound 8 was studied by performing reactions with primary amines, which resulted in a series of five carboxamides (9) with yields from 45% to 90%. The compound 7 was also reacted with hydrazines, using alcohols as solvent. As a result it was obtained a new series of 7-alkoxy-2,3-dihydrofuro[2,3-d]pyridazines (13) with yields from 33% to 70%. All synthesized compounds were characterized by nuclear magnetic resonance and mass spectrometry. Este trabalho apresenta os resultados relativos ao estudo da reatividade dos 3-ciano-acrilatos de etila (3), obtidos através da metodologia de olefinação de Horner-Wadsworth-Emmons (HWE) de cetonas α,β-insaturadas (1) com o cianometilfosfonato de dietila (2). Foram sintetizadas oito moléculas, sendo sete inéditas, de 6-aril-4-etoxicarbonil-2H-piran-2-onas (4) através da reação de autocondensação dos 4-aril-2-cianometileno-4-metóxi-but-3-enoatos de etila (3), sob refluxo de solução aquosa de ácido clorídrico, obtendo os produtos com rendimentos de 15% a 66%. Uma série inédita de seis 7-alquil-5-cianometil-3,4,7,7a-tetrahidropirano[2,3-b]pirrol-6(2H)-onas (6) foi sintetizada através da reação da 3-ciano-2-(5,6-dihidro-2H-piran-3-il)acrilato de etila (3) com aminas primárias (5), livre de solventes e catalizadores, com rendimentos de 55% a 75%. Observou-se que o 2-(4,5-dihidrofuran-3-il)-2-oxoacetato de etila (1j) sofre rearranjo espontâneo com a formação do 3-formil-4,5-dihidrofurano-2-carboxilato de etila (7). Posteriormente, foi estudada as condições ideais para a conversão controlada do composto 1j para o 7. O composto inédito 7 foi submetido a reação de olefinação com cianometilfosfonato de dietila a qual forneceu o 3-(2-cianovinil)-4,5-dihidrofuran-2-carboxilato de etila (8). O composto 8 foi utilizado como precursor em reações com aminas primária onde foi obtido uma série de cinco carboxamidas (9) com rendimentos de 45% a 90%. A reatividade do composto 7 foi também avaliada em reações com hidrazinas, utilizando álcoois como solvente, fornecendo uma série inédita de 7-alcóxi-2,3-dihidrofurano[2,3-d]piridazinas (13) com rendimentos de 33% a 70%. As substâncias sintetizadas neste trabalho foram caracterizadas e identificadas por ressonância magnética nuclear e espectrometria de massas.

The novel calcium sensitizer and ATP-dependent potassium channel opener levosimendan has been introduced for routine use in several European countries. Recent reports on clinical experience confirm the positive hemodynamic results and beneficial clinical effects described in the initial dose-finding and randomized comparative therapeutic trials in patients with severe low-output heart failure. In addition, studies in small series of patients with cardiogenic shock after myocardial infarction and/or surgical interventions and post-interventional myocardial dysfunction (stunning) indicate that the inotropic and vasodilating actions of levosimendan may be of value in a wider range of indications. Dose recommendations, combination with other drugs, and potential side effects are discussed in this overview.