6844-34-4Relevant articles and documents
Connective synthesis of 5,5-disubstituted hydantoins by tandem α-amination and α-arylation of silyl ketene acetals
Saunthwal, Rakesh K.,Cornall, Matthew T.,Abrams, Roman,Ward, John W.,Clayden, Jonathan
, p. 3408 - 3412 (2019/03/21)
5,5-Disubstituted hydantoins, formally the cyclisation products of quaternary amino acids, were formed connectively from simple ester-derived starting materials by a one-pot tandem method. Amination of the silyl ketene acetal derivative of a methyl ester takes place by silver-catalysed addition to the N═N bond of an azocarboxamide, generating a N-amino-N′-aryl urea derivative of a substituted aminoester. Treatment with a base forms an ester enolate which undergoes arylation by intramolecular migration of an aryl ring to the α-position of the ester. The product undergoes ring closure to a hydantoin, which may itself be deprotected and functionalised. Aryl migration is successful with rings of various electronic character and with esters bearing functionalised and unfunctionalised chains, and the products have features in common with several bioactive compounds.
SAR-studies on the importance of aromatic ring topologies in search for selective 5-HT7 receptor ligands among phenylpiperazine hydantoin derivatives
Handzlik, Jadwiga,Bojarski, Andrzej J.,Sata?a, Grzegorz,Kubacka, Monika,Sadek, Bassem,Ashoor, Abrar,Siwek, Agata,Wi?cek, Ma?gorzata,Kucwaj, Katarzyna,Filipek, Barbara,Kie?-Kononowicz, Katarzyna
, p. 324 - 339 (2014/04/17)
The current study is focused on newly developed phenylpiperazine derivatives of aromatic methylhydantoin differing in mutual positions of methyl and phenyl moieties. The new compounds were synthesized using Bucherer-Bergs reaction, two-phase alkylation, Mitsunobu reaction and/or an alkylation under microwave irradiation. The compounds developed were assessed on their affinity for serotoninergic receptors 5-HT1A, 5-HT6, 5-HT 7 and α1-ARs in radioligand binding assays. Selected compounds were tested on their inhibitory effect at human 5-HT3A expressed in Xenopus Oocytes as well as on their activity at α1-adrenoceptor subtypes in functional and electrophysiological bioassays, respectively. Most of investigated compounds exhibited affinities for α1-ARs, 5-HT1A, 5-HT7 (Ki ~ 0.8-353 nM) significantly higher than those for 5-HT6 receptors. Very weak inhibitory effect at 5-HT3A accompanied with high activity at α1D-AR subtypes were observed for selected representative compounds. Among the current series, particularly 5-(4-fluorophenyl)-3-(2-hydroxy-3-(4-(2-methoxyphenyl)piperazin-1-yl)propyl) -5-methylimidazolidine-2,4-dione hydrochloride (25a) displayed the highest 5-HT7 affinity with Ki = 3 nM and selectivity with 40-3600 fold towards 5-HT1A, 5-HT6, and α1-ARs.
Racemic and Optically Active Hydantoins from Disubstituted Cyanoacetic Acids
Knabe, Joachim,Wunn, Wolfgang
, p. 538 - 543 (2007/10/02)
Starting from the chiral disubstituted cyanoacetic acids 1 the racemates and some enantiomers of the 5,5-disubstituted hydantoins 6 and of the 3-methylhydantoins 7 are synthesized via the isocyanates 3.Their absolute configurations are determined.