- An Improved Protocol for Synthesis of 3-Substituted 5-Arylidene-2-thiohydantoins: Two-step Procedure Alternative to Classical Methods
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A novel method for the direct synthesis of 5-arylidene-2-thiohydantoins from thioureas and aromatic aldehydes in the presence of base in ethanol was developed. Application of this efficient method allowed preparing thiohydantoins, which are difficult to s
- Kuznetsova, Olga Yu,Antipin, Roman L.,Udina, Anna V.,Krasnovskaya, Olga O.,Beloglazkina, Elena K.,Terenin, Vladimir I.,Koteliansky, Victor E.,Zyk, Nikolay V.,Majouga, Alexander G.
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p. 1570 - 1577
(2016/09/24)
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- Substituted 2-thioxoimidazolidin-4-ones and imidazolidine-2,4-diones as fatty acid amide hydrolase inhibitors templates
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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.
- Muccioli, Giulio G.,Fazio, Nicola,Scriba, Gerhard K. E.,Poppitz, Wolfgang,Cannata, Fabio,Poupaert, Jacques H.,Wouters, Johan,Lambert, Didier M.
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p. 417 - 425
(2007/10/03)
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- Synthesis of 3-ω-amino-2-thiohydantoins
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In the reaction of ethyl isothiocyanatoacetate with diamines, followed by cyclization of the intermediate product, 3-monosubstituted thiohydantoins have been obtained. It was found that the reaction course depends on the purity of the isothiocyanate used and also, in the case of dialkylaminoamines, the self-cyclization occurs. Besides the dialkylamino derivatives of 3-monosubstituted 2-thiohydantoins also new monoalkylamino, amino and heterocyclic derivatives were synthesized. The aryldiazonium derivative of 3-monosubstituted 2-thiohydantoin yielded both respective phenol derivative after hydrolysis and the product of coupling with 2-naphthol.
- Ryczek, Jozef
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p. 665 - 670
(2007/10/03)
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- A New Method of Synthesis of 3-Monosubstituted-2-thiohydantoins and -Hydantoins
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A new method of synthesis of 3-monosubstituted derivatives of 2-thiohydantoin and hydantoin in reaction of isothiocyanate or isocyanate glycin ethyl ester with primary aliphatic and aromatic amines has been described. Crude products were obtained with high yield and purity. The structure of these compounds was confirmed by spectral methods. Key words: 2-thiohydantoin, hydantoin, isothiocyanate glycin ethyl ester, isocyanate glycin ethyl ester
- Ryczek, J.
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p. 2599 - 2604
(2007/10/02)
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- BASE CATALYZED CYCLIZATION OF SUBSTITUTED ESTERS OF HYDANTOIC AND THIOHYDANTOIC ACID
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Base catalyzed cyclization rates have been measured of 22 derivatives of hydantoic and thiohydantoic acid esters in water and methanol.The cyclization of methyl and ethyl esters of hydantoic and 5-methylhydantoic acids is accompanied by hydrolysis of the ester group, whereas with the other derivatives the hydrolysis does not take place.Hydrolysis of the cyclization products (hydantoin and thiohydantoin derivatives) is not significant under the kinetic conditions.The cyclization of methyl ester of 5-phenylhydantoic acid in methanol is reversible; the equilibrium mixture contains 30percent of the starting ester.In all the cases the cyclization is subject to specific base catalysis; exceptions are esters of 5-phenylthiohydantoic and 5-phenyl-2-methylthiohydantoic acids whose cyclizations are subject to general base catalysis.Substituents always accelerate the cyclization.The 3-substituents have the greatest effects, the cyclization rate being considerably increased with bulk of the substituents; similarly large effect of 5-phenyl group consists mainly in its polar effects on the pre-equilibrium.The cyclizations are slower in methanol at the same concentration of the lyate ion: the greatest difference (up to 3 orders of magnitude) is observed with the 5-phenyl derivatives.
- Kavalek, Jaromir,Machacek, Vladimir,Svobodova, Gabriela,Sterba, Vojeslav
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p. 375 - 390
(2007/10/02)
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