Synthesis and Pharmacological Evaluation of Novel Potential Ultrashortacting β‐Blockers.

Abstract

Carboxylic acid esters Carboxylic acid esters Q 0530Synthesis and Pharmacological Evaluation of Novel Potential Ultrashortacting β-Blockers. -Eight new derivatives of β-adrenergic receptor blocking phenoxyaminopropanols such as (VIII) are prepared by a four-step synthesis. Incorporation of an ester group between the aromatic and amine moiety of the connecting chain leads to a decrease of the β-adrenergic receptor blocking activity of the original compounds. All the compounds show moderate antiisoprenaline activity and antiarrhythmic activity. The cardioselectivity is low for methyl-and ethylcarbonyl derivatives but increases significantly for propyl-and butylcarbonyl derivatives. -(MOKRY, P.; ZEMANOVA, M.; CSOELLEI*, J.; RACANSKA, E.; TUMOVA, I.; Pharmazie 58 (2003) 1, 18-21; Inst. Chem. Drugs, Fac. Pharm., Univ. Vet. Pharm. Sci., Brno, Czech Republic; Eng.) -H. Hoennerscheid 21-090

Effect of Newly Synthesized Compounds 44Bu and 444 on QRS-Complex Width and Fast Sodium Current: Differences between Isomers

“…The chemical structure of 44Bu and 444 was verified by the elementary analysis, IR, 1 H-NMR and 13 C-NMR spectroscopy (Mokrý et al 2001), purity was verified chromatographically (Mokrý et al 2003), and elementary physical characteristics were determined (Opatrilova et al 2005).…”

“…The compounds with draft names 44Bu and 444, which were tested in this study, are derivates of aryl-carbonyl-oxy-amino-propanols varying in the substituent in the aliphatic chain; 44Bu contains n-butyl whereas 444 terc-butyl ( Fig. 1; Mokrý et al 2003). 44Bu was reported to suppress the aconitine-induced arrhythmias more efficiently than lidocaine, a class-Ib antiarrhythmic drug (Bartosova et al 2007).…”

Evaluation of Stability of Potential Betaadrenolytics in Various Solutions by thin Layer Chromatography and by Kinetics of Hydrolysis

“…The substitution on secondary nitrogen atom of beta-adrenergic receptor blockers with such group gives the molecule the affinity to both types of adrenergic receptor: alfa and beta such as carvedilol (Graham & Patric, 2009 (Graham & Patric, 2009, Griffith, 2003. These potential drugs may be also indicated at supraventricular tachycardia, at fibrillation, hypertension and at acute myocardial infarction (Mokrý et al, 2003) Because the hydrolysis is the most frequent reaction in the degradation process of the esters, the stability study of such compounds in different media is very important. The ester functional group is more labile than the ethereal connecting chain.…”

“…The studied compounds are derivatives of [(arylcarbonyl)oxy]aminopropanol, with carbamate substitution on a benzene ring. The compounds are potential ultra-short acting beta-adrenergic receptor blocking agents which were prepared at the Institute of Chemical drugs of the University of Veterinary and Pharmaceutical Sciences Brno, Czech Republic (Mokrý et al, 2003. The list of studied compound is shown in Table 1.…”

Synthesis and Characterization of New 3-(4-Arylpiperazin-1-yl)-2-hydroxypropyl 4-Propoxybenzoates and Their Hydrochloride Salts

“…The phenylpiperazine segment, the basic part of the molecule, is either unsubstituted or substituted with a methoxy or a fluoro moiety in the C (2) 1 or C (4) 1 position. Drugs used in clinical practice [3][4][5][6] as well as investigational agents [9][10][11] are characterized by similar structural features [2]; nevertheless, the biological effects of the discussed salts of 3-(4-arylpiperazin-1-yl)-2-hydroxypropyl 4-propoxybenzoates have not been determined so far.…”