Synthesis, antiarrhythmic and hypotensive activity of some novel 1,3-disubstituted ureas and phenyl N-substituted carbamates

Chalina, E.; Chakarova, Lidia; Staneva, D

doi:10.1016/s0223-5234(99)80023-3

Cited by 15 publications

(6 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The mechanism of action of MC450 is similar to that described for the two previously reported ureas NS-1643 and NS-3623, thus corroborating the role of the urea scaffold as a useful chemotype in the quest for hERG openers. [28] Starting from the observation that the hERG channel is involved in cardiac disorders and very few and even old studies have been devoted to the evaluation of the cardiac activity of ureabased compounds so far, [29][30][31][32][33][34][35] we aimed to explore the cardiovascular effect of MC450, together with its SS enantiomer and the RS (meso) form to gain insight on a possible stereoselective behavior. These compounds were prepared in high optical purity by an alternative and more efficient stereospecific route than what was previously reported for the RR enantiomer.…”

Section: Introductionmentioning

confidence: 99%

hERG stereoselective modulation by mexiletine‐derived ureas: Molecular docking study, synthesis, and biological evaluation

Milani

Budriesi

Tavazzani

et al. 2023

Archiv der Pharmazie

View full text Add to dashboard Cite

Long QT syndrome (LQTS) is a disorder of cardiac electrophysiology resulting in life‐threatening arrhythmias; nowadays, only a few drugs are available for the management of LQTS. Focusing our attention on LQT2, one of the most common subtypes of LQTS caused by mutations in the human ether‐à‐go‐go‐related gene (hERG), in the present work, the stereoselectivity of the recently discovered mexiletine‐derived urea 8 was investigated on the hERG potassium channel. According to preliminary in silico predictions, in vitro studies revealed a stereoselective behavior, with the meso form showing the greatest hERG opening activity. In addition, functional studies on guinea pig isolated left atria, aorta, and ileum demonstrated that 8 does not present any cardiac or intestinal liability in our ex vivo studies. Due to its overall profile, (R,S)‐8 paves the way for the design and development of a new series of compounds potentially useful in the treatment of both congenital and drug‐induced forms of LQTS.

show abstract

Section: Introductionmentioning

confidence: 99%

hERG stereoselective modulation by mexiletine‐derived ureas: Molecular docking study, synthesis, and biological evaluation

Milani

Budriesi

Tavazzani

et al. 2023

Archiv der Pharmazie

View full text Add to dashboard Cite

show abstract

“…[4][5][6] Ureas bearing heterocyclic substitutents, for example 1,3,4-thiadiazole, 2492 L.-Q. Chai et al have been shown to exert anti-inflammatory, [7][8][9] antibacterial, 10 and anticonvulsant activities.…”

Section: Introductionmentioning

confidence: 99%

One-Pot Synthesis of Phenylallyl Substituted Unsymmetrical Ureas Under Microwave Irradiation

Chai

Chen

Wang

et al. 2007

Phosphorus, Sulfur, and Silicon and the Related Elements

View full text Add to dashboard Cite

A series of phenylallyl-substituted unsymmetrical ureas were synthesized in a onepot procedure by reactions of cinnamoyl isocyanate, which was prepared from cinnamoyl azide by Curtius rearrangement, with various aromatic amines, 2-amino-5-aryl-1,3,4-thiadiazoles and 2-amino-5-aryloxymethylene-1,3,4-thiadiazoles under microwave irradiation. Compared to conventional methods, this synthesis has the advantages of mild reaction conditions, easy handling, and high yields. The products have been characterized by analytical and spectral (IR and 1 H NMR) data.

show abstract

“…Many esters of alkoxyphenylcarbamic acids exhibit various, e.g. local anaesthetic [I, 2, 31, antiarrhythmic [4], antiulcer [5], antimycobacterial [6] and other activities [7]. In connection with systematic investigations in the group of basic (2a-2k), which were prepared by reaction of 2,3-epoxypropan-1-01 with corresponding 2-, 3-or 4-alkoxysubstituted phenylisocyanates (la-I k), and then isolated as the salts (4-4k) with hydrochloric acid (Scheme) according to similar procedure which was described in the literature [8].…”

Section: Introductionmentioning

confidence: 99%

Synthesis, physico-chemical properties and bioloclical activitv of 1-(4-fluorophenvl)-4-[3-(2-,3- and 4-alkyloxyphenylcarbamoyloxy)-2-hydroxypropyl] piperaziniumchlorides

et al. 2004

View full text Add to dashboard Cite

1-(4-fluoropheny1)-4-[3-(2-,3- and 4-alkyloxyphenylcarbamoyloxy)-2-hydroxypropyl]piperaziniumchlorides, with one to four carbon atoms in the alkoxy group on aromatic ring have been synthesized as the derivatives of substituted phenylcarbamic acid. The structures were confirmed by their spectral data. Potential antiarrhythmic activity was evaluated in guinea-pigs model. Preliminary studies demonstrated that the evaluated compounds, using ouabain arrhythmia model, appear to possess only moderate antiarrhythmic activity. Only compound marked as 4f appears to be more potent and lead us to focus our attention on structures with more bulky substituent in the m-position at aromatic ring in the hydrophilic part of molecule.

show abstract

Synthesis, antiarrhythmic and hypotensive activity of some novel 1,3-disubstituted ureas and phenyl N-substituted carbamates

Cited by 15 publications

References 6 publications

hERG stereoselective modulation by mexiletine‐derived ureas: Molecular docking study, synthesis, and biological evaluation

hERG stereoselective modulation by mexiletine‐derived ureas: Molecular docking study, synthesis, and biological evaluation

One-Pot Synthesis of Phenylallyl Substituted Unsymmetrical Ureas Under Microwave Irradiation

Synthesis, physico-chemical properties and bioloclical activitv of 1-(4-fluorophenvl)-4-[3-(2-,3- and 4-alkyloxyphenylcarbamoyloxy)-2-hydroxypropyl] piperaziniumchlorides

Contact Info

Product

Resources

About