23186-92-7Relevant articles and documents
Computer-aided studies for novel arylhydantoin 1,3,5-triazine derivatives as 5-HT6 serotonin receptor ligands with antidepressive-like, anxiolytic and antiobesity action in vivo
Kurczab, Rafal,Ali, Wesam,?azewska, Dorota,Kotánska, Magdalena,Jastrzebska-Wiesek, Magdalena,Sata?a, Grzegorz,Wiecek, Ma?gorzata,Lubelska, Annamaria,Latacz, Gniewomir,Partyka, Anna,Starek, Ma?gorzata,Dabrowska, Monika,Weso?owska, Anna,Jacob, Claus,Kiéc-Kononowicz, Katarzyna,Handzlik, Jadwiga
, (2018/10/20)
This study focuses on the design, synthesis, biological evaluation, and computer-aided structure-activity relationship (SAR) analysis for a novel group of aromatic triazine-methylpiperazines,with an hydantoin spacer between 1,3,5-traizine and the aromatic fragment. New compounds were synthesized and their affinities for serotonin 5-HT6, 5-HT1A, 5-HT2A, 5-HT7, and dopamineD2 receptorswere evaluated. The induced-fit docking (IFD) procedure was performed to explore the 5-HT6 receptor conformation space employing two lead structures. It resulted in a consistent binding mode with the activity data. For the most active compounds found in each modification line, anti-obesity and anti-depressive-like activity in vivo, as well as "druglikeness" in vitro, were examined. Two 2-naphthyl compounds (18 and 26) were identified as themost active 5-HT6R agents within each leadmodification line, respectively. The 5-(2-naphthyl)hydantoin derivative 26, themost active one in the series (5-HT6R: Ki = 87 nM), displayed also significant selectivity towards competitive G-protein coupled receptors (6-197-fold). Docking studies indicated that the hydantoin ring is stabilized by hydrogen bonding, but due to its different orientation, the hydrogen bonds formwith S5.44 and N6.55 or Q6.58 for 18 and 26, respectively. Compound 26 exerted anxiolytic-like and antidepressant-like activities. Importantly, it demonstrated anti-obesity properties in animals fed palatable feed, and did not show toxic effects in vitro.
Ultrasound-enhanced green synthesis of 5,5-diphenylhydantoin derivatives using symmetrical or unsymmetrical benzils
Safari, Javad,Moshtael Arani, Naimeh,Anousheh Isfahani, Ramezan
experimental part, p. 255 - 258 (2010/10/19)
A rapid, highly efficient and mild green synthesis of 5,5-diphenylhydantoin derivatives was achieved from the reaction of symmetrical or unsymmetrical benzil derivatives with urea in the presence of ethanolic KOH under ultrasound irradiation. This simple method affords 5,5-diphenylhydantoin derivatives at room temperature in short reaction time with high yield and purity. This study aimed to overcome the limitations and drawbacks of the reported methods such as tedious work-up, low yield and long reaction time.
A rapid and efficient microwave-assisted synthesis of hydantoins and thiohydantoins
Muccioli, Giulio G.,Poupaert, Jacques H.,Wouters, Johan,Norberg, Bernadette,Poppitz, Wolfgang,Scriba, Gerhard K.E.,Lambert, Didier M.
, p. 1301 - 1307 (2007/10/03)
The present paper describes studies on the synthesis of the antiepileptic drug phenytoin, and of structurally related derivatives. First, the influence of the solvent has been investigated in the microwave-assisted synthesis of the drug, resulting in a yield improvement and a cleaner reaction. Second, a two-step reaction is described to synthesize selectively and in high yields phenytoin. The first step consists in microwave activation of the reaction of benzil with thiourea, the second step includes the conversion of the resulting 2-thiohydantoin to phenytoin using hydrogen peroxide. Moreover, microwave activation is a very convenient method for the synthesis of 3-alkylated phenytoin derivatives, resulting in a much more selective method than the previously reported procedure using alkylating agents.
