[Synthesis of 2-{3-[4-(4-fluorophenyl)-1-piperazinyl]-2-hydroxy-propoxy}-phenylcarbamic acid alkylesters and in vitro evaluation of their beta-antiadrenergic and vasodilatative activities]. / Syntéza alkylesteru kyseliny 2-{3-[4-(4-fluorfenyl)-piperazin-1-yl]-2-hydroxy- propoxy}-fenylkarbamové a in vitro : . ' hodnoceni jejich beta-antiadrenergní a vazodilatacní aktivity.

Synthesis of 2-{3-[4-(4-fluorophenyl)-1-piperazinyl]-2-hydroxy-propoxy}-phenylcarbamic acid alkylesters and in vitro evaluation of their beta-antiadrenergic and vasodilatative activities In effort to obtain effective compounds able to favourably influence pathologically changed cardiovascular functions, such as hypertension and ischemic cardiac disease, a new series of aryloxyaminopropanols were synthesized. Four of the compounds, which differ in the alkyl substitution of phenylcarbamate (methyl, ethyl, propyl, butyl), were chosen for basic in vitro pharmacological analyses. In experiments on the isolated spontaneously beating guinea pig atria all compounds at conc. of 1.0.10(-6) mol.l(-1) decreased the basic heart rate (7.6-13.6%) and inhibited the positive chronotropic effect of isoprenaline (pA2 = 6.28-6.81). The compounds manifest only a slight relaxation effect on KCl pre-contracted aortal strips of rats (not until conc. of 1.0.10(-5) mol.l(-1)). The compounds with propyl and butyl substitution appear more effective than the methyl and ethyl derivatives.

[Study of a newly synthesized substance with a potential to stimulate beta3-adrenergic receptors]. / Testování nove syntetizované látky s potencionálním beta-adrenergne agonistickým úcinkem.

beta3-Adrenoreceptor agonists can stimulate lipolysis in the white adipose tissue and thermogenesis in the brown adipose tissue. These activities could be useful in the treatment of obesity and the associated metabolic syndrome. The effects of six-week oral administration of the newly synthesized substance B496 (methyl-4-[2-[2-hydroxy-3-(4-ethylcarbamoyl)phenoxyprophyl]amino]etyl)-phenoxyacetate hydrochloride) on serum glucose, triglycerides, total cholesterol, and leptin levels were studied in male Wistar rats fed with a high-fat diet. The animals were divided into a group treated with B496 (5 mg dissolved in 1 litre of water) and a control group. The results indicated a significant reduction in serum glucose levels (-26 %, p<0,01), triacylglyceride levels (-21 %, p<0,05) and leptin levels (-43 %, p<0,01). Further the effect of a single intraperitoneal dose (1 mg/kg) of B496 and BRL-37344 on serum leptin levels in the C57Bl/6J mouse was investigated. Administration of BRL-37344 resulted in a significant decrease in serum leptin levels (-55 %, p<0,001). This reduction was not demonstrated by newly synthesized substance B496.