No abstract

Stereochemical Studies of Some 12a-Substituted Rotenoid Derivatives.-The absolute configuration of some title compounds like (I) and (II) is determined by means of 1H NMR, CD and molecular mechanics studies. -(KOSTOVA, I.; BEROVA, N.; IVANOV, P.; MIKHOVA, B.; RAKOVSKA, R.; SNATZKE, G.; Croat.

The protein binding of piroxicam, a widely used non-steroidal anti-inflammatory drug has been investigated by high-performance liquid affinity chromatography, with phenylbutazone and diazepam used as markers for binding-site characterization, and by circular dichroism titration. It was found that piroxicam binds to high-affinity phenylbutazone-binding sites and to high-affinity diazepam-binding sites. No binding to the low-affinity sites of either marker was established. High values of the primary (high-affinity) binding constants corresponding to both types of binding site were obtained by means of a mathematical method cited in the literature. The circular dichroic spectra of piroxicam were studied at a given albumin concentration and various drug concentrations. A new Cotton effect was observed and was ascribed to the binding of piroxicam to the protein molecule. The values of differential molar ellipticity (delta theta) were treated by a new mathematical procedure for analysis of the data obtained. A high affinity constant was calculated for one class of binding site. Its value is in good agreement with the values obtained by affinity chromatography. These results reveal that circular dichroism is an acceptable method for investigation of protein binding.

The absolute configuration of the 2-(phenylmethy1)pyridine derivatives 1-9 had been established by X-ray diffraction and chemical correlation. Their CD spectra have been studied in different solvents for the free and protonated forms. It has now been found that, from the sign of the strong CD couplet between 270 and 220 nm, which was observable for all these compounds besides 7 and 9, their absolute configuration can be determined much quicker.

The racemic and optically active 4'- and 8-substituted tetrahydroisoquinolines 2-5 have been synthesized and their effect on the water-immersion stress ulcer in rats has been studied. All compounds prevent the formation of stress ulcer, the strongest effect being exhibited by compound 4 and its dextrarotatory isomer (R1 = Cl, R2 = NHCOOC2H5). The antiulcer activity of 4 is 30 to 50 times higher than that of the H2 receptor antagonists Cimetidin and Ranitidin used for comparison. The absolute configuration of the optically active compounds 2, 3 and 4 has been determined by means of chemical correlation. The antiulcer activity of 4 is characterized by enantioselectivity, S-(+)-4 is three times as active than R-(-)-4.