85369-75-1Relevant academic research and scientific papers
Substituted 2-thioxoimidazolidin-4-ones and imidazolidine-2,4-diones as fatty acid amide hydrolase inhibitors templates
Muccioli, Giulio G.,Fazio, Nicola,Scriba, Gerhard K. E.,Poppitz, Wolfgang,Cannata, Fabio,Poupaert, Jacques H.,Wouters, Johan,Lambert, Didier M.
, p. 417 - 425 (2006)
The demonstration of the essential role of fatty acid amide hydrolase (FAAH) in hydrolyzing endogenous bioactive fatty acid derivatives has launched the quest for the discovery of inhibitors for this enzyme. Along this line, a set of 58 imidazolidine-2,4-dione and 2-thioxoimidazolidin-4-one derivatives was evaluated as FAAH inhibitors. Among these compounds, 3-substituted 5,5′-diphenylimidazolidine-2,4-dione and 3-substituted 5,5′-diphenyl-2-thioxoimidazolidin-4-one derivatives were previously described as CB1 cannabinoid receptor ligands. In the present study, we synthesized several derivatives exhibiting interesting FAAH inhibitory activity and devoid of affinity for the CB1 and CB2 cannabinoid receptors. For instance, 3-heptyl-5,5′-diphenylimidazolidine- 2,4-dione (14) and 5,5′-diphenyl-3-tetradecyl-2-thioxo-imidazolidin-4-one (46) showed p/50 values of 5.12 and 5.94, respectively. In conclusion, it appears that even though several 3-substituted 5,5′-diphenyl-2-thioxoimidazolidin-4-one and 3-substituted 5,5′-diphenylimidazolidine-2,4-dione derivatives have been previously shown to behave as CB1 cannabinoid receptor ligands, appropriate substitutions of these templates can result in FAAH inhibitors devoid of affinity for the cannabinoid receptors.
KINETICS AND MECHANISM OF BASE-CATALYZED CYCLIZATION OF SUBSTITUTED AMIDES AND NITRILES OF HYDANTOIC ACID
Machacek, Vladimir,Svobodova, Gabriela,Sterba, Vojeslav
, p. 140 - 155 (2007/10/02)
Rates of base-catalyzed cyclizations of 8 substituted derivatives of hydantoic acid amide type R3-NH(5)-CO(4)-NR2(3)-CH2(2)-CO(1)-NHR1 and 9 nitriles type R3-NH(5)-CO(4)-NR2(3)-CHR1(2)-CN have been measured in aqueous and methanolic media.The cyclization of the amides in aqueous medium is also accompanied by hydrolysis of the hydantoins formed.In some cases the hydrolysis rate constant is greater than the corresponding cyclization reaction rate constant.With the least reactive amides, the cyclization is also accompanied by hydrolysis of the amide group.The ra te of the cyclization reactions in water is higher than that in methanol (at the same concentration of the lyate ions) by the factor of 10 - 100.Substitution of hydrogen at 3 and 5 positions by methyl or phenyl groups causes an acceleration of the cyclization reaction, whereas a substitution in the amide group causes a considerable retardation.The greatest acceleration of the cyclization (by as much as 4 orders) is caused by introduction of phenyl group to the N(5) position, which is due to a substantial increase of concentration of the reactive anion.
SYNTHESIS AND NITROSATION OF 3- AND 3,5-SUBSTITUTED HYDANTOINS
Klimavichyus, K.-A. V.,Lutsenko, V. V.,Paulauskaite, G. V.,Mikul'skis, P. P.,Bal'chitis, G. A.,Ionushauskas, S. L.
, p. 1160 - 1162 (2007/10/02)
The cyclization of N-alkylated(arylated) α-ureidocarboxylic acids gives a series of 3-mono- and 3,5-disubstituted hydantoins, and nitrosation of the latter yields their nitroso derivatives.The rotational isomerism of 3-(α-naphthyl)hydantoins has been stud
