7341-63-1Relevant articles and documents
Facile synthesis of phthalidyl fused spiro thiohydantoins through silica sulfuric acid induced oxidative rearrangement of ninhydrin adducts of thioureas
Mandal, Subhro,Pramanik, Animesh
, (2019/12/24)
A one-pot three-component sequential synthetic protocol produces structurally and biologically important phthalidyl fused spiro N,N′-disubstituted thiohydantoins from readily available aromatic isothiocyanates, primary amines and ninhydrin. In this three-step synthesis while the initial two steps are catalyst-free, in the final step silica sulfuric acid (SSA) induces an oxidative rearrangement in [3.3.0]-bicyclic 1,2-diol adducts of ninhydrin and thioureas under solvent-free condition to generate the final products spiro-fused thiohydantoins. The adequate acidity of SSA in cooperation with moderate oxidizing property promotes a facile oxidative rearrangement in 1,2-diol intermediates to produce the spiro-fused thiohydantoins with diverse functionalities. Easy recyclability of SSA, good to excellent yield of the products, wider substrate scope, shorter reaction time, solvent-free two steps out of three and high atom economy make this method attractive and practicable.
Reactions of N-alkenyl Thioureas with p-alkoxyphenyltellurium Trichlorides
Kut, Mykola,Fizer, Maksym,Onysko, Mikhajlo,Lendel, Vasil
, p. 2284 - 2290 (2018/09/06)
N-Аlkenyl thioureas, under the action of aryltellurium trichlorides, form the addition products N-{2-chloro-3-[dichloro(4-alkoxyphenyl)-tellanyl]propyl} thioureas or the intramolecular cyclization products 5-{dichloro(4-alkoxyphenyl)-telluromethyl}-2-phenylamino-4,5-dihydro-1,3-thiazole hydrochlorides. The reaction route depends on the nature of the substituent in the thiourea. The Fukui function reactivity indexes identify the electrophilic/nucleophilic centers and explain the possible cyclization reaction in the case of phenyl substituted thioureas. In the case of other substituents, the calculated values of partial atomic charges clearly predict that the addition reaction is more possible.
Synthesis, molecular docking and biological evaluation of N,N-disubstituted 2-aminothiazolines as a new class of butyrylcholinesterase and carboxylesterase inhibitors
Makhaeva, Galina F.,Boltneva, Natalia P.,Lushchekina, Sofya V.,Serebryakova, Olga G.,Stupina, Tatyana S.,Terentiev, Alexey A.,Serkov, Igor V.,Proshin, Alexey N.,Bachurin, Sergey O.,Richardson, Rudy J.
, p. 1050 - 1062 (2016/02/19)
A series of 31 N,N-disubstituted 2-amino-5-halomethyl-2-thiazolines was designed, synthesized, and evaluated for inhibitory potential against acetylcholinesterase (AChE), butyrylcholinesterase (BChE) and carboxylesterase (CaE). The compounds did not inhibit AChE; the most active compounds inhibited BChE and CaE with IC50 values of 0.22-2.3 μM. Pyridine-containing compounds were more selective toward BChE; compounds with the para-OMe substituent in one of the two dibenzyl fragments were more selective toward CaE. Iodinated derivatives were more effective BChE inhibitors than brominated ones, while there was no influence of halogen type on CaE inhibition. Inhibition kinetics for the 9 most active compounds indicated non-competitive inhibition of CaE and varied mechanisms (competitive, non-competitive, or mixed-type) for inhibition of BChE. Docking simulations predicted key binding interactions of compounds with BChE and CaE and revealed that the best docked positions in BChE were at the bottom of the gorge in close proximity to the catalytic residues in the active site. In contrast, the best binding positions for CaE were clustered rather far from the active site at the top of the gorge. Thus, the docking results provided insight into differences in kinetic mechanisms and inhibitor activities of the tested compounds. A cytotoxicity test using the MTT assay showed that within solubility limits (30 μM), none of the tested compounds significantly affected viability of human fetal mesenchymal stem cells. The results indicate that a new series of N,N-disubstituted 2-aminothiazolines could serve as BChE and CaE inhibitors for potential medicinal applications.
