23747-91-3Relevant academic research and scientific papers
Synthesis and anticonvulsant activity of new N-1′,N-3′-disubstituted-2′H,3H,5′H-spiro-(2-benzofuran-1,4′-imidazolidine)-2′,3,5′-triones
Patel, Hardik J.,Sarra, Joe,Caruso, Francesco,Rossi, Miriam,Doshi, Utkarsh,Stephani, Ralph A.
, p. 4644 - 4647 (2006)
Thirteen new N-1′,N-3′-disubstituted-2′H,3H,5′H-spiro-(2-benzofuran-1,4′-imidazolidine)-2′,3,5′-triones were synthesized and their pharmacological activity determined with the objective to better understand their SAR for anticonvulsant activity. The anticonvulsant effects of these compounds were evaluated by standard pentylenetetrazol (scPTZ test) and maximum electroshock seizure (MES test) models in mice. Most of the compounds showed ability to protect against the pentylenetetrazol-induced convulsions. Compound 3o (the N-1′-p-nitrophenyl, N-3′-ethyl derivative) in the N-1′-aryl, N-3′-alkyl disubstituted series exhibited maximum activity with ED50 of 41.8 mg/kg in scPTZ convulsion model.
Multicomponent, one-pot sequential synthesis of 1,3,5- and 1,3,5,5-substituted barbiturates
Volonterio, Alessandro,Zanda, Matteo
, p. 7486 - 7497 (2008/12/22)
(Chemical Equation Presented) Carbodiimides and malonic acid monoethylesters readily react to afford N-acylurea derivatives that could be cyclized in situ by addition of a suitable base. This process represents a general and straightforward one-pot sequential synthesis of 1,3,5-trisubstituted barbiturates in very mild conditions (organic solvent/2 N NaOH aqueous solution, 20°C). Performing the reaction in the presence of an electrophile resulted in the formation of fully substituted (namely, 1,3,5,5- tetrasubstituted) barbiturates through a three-component one-pot sequential process. The latter, however, occurred only with highly reactive electrophiles, such as benzyl and, in some instances, allyl halides. In order to expand the scope of the process, we sought to develop a general method for the C-alkylation of 1,3,5-trisubstituted barbiturates. We found that C-alkylation occurred upon treatment of 1,3,5-trisubstituted barbiturates with an alkyl halide in CH 3CN at 120°C in the presence of anhydrous K2CO 3 affording the target 1,3,5,5-tetrasubstituted barbiturates in good yields. The multicomponent process was accomplished by combining the three steps in a one-pot sequential fashion, i.e., the condensation of carbodiimides with malonic acid monoethylesters, the cyclization of the resulting N-acylureas, and the C-alkylation of the resulting 1,3,5-substituted barbiturates. A detailed study of the influence of the structure of the reactants on the reaction outcome and mechanism is presented. By selective N′-deprotection of 1,3,5,5-tetrasubstituted barbiturates, the corresponding 1,5,5-trisubstituted barbiturates were also prepared.
