α1 - adrenolytic activities of pyridoindole derivatives recently synthesized in the Institute of Experimental Pharmacology, Slovak Academy of Sciences, were measured. A characteristic set of derivatives (five active, one with a threshold activity and two inactive) was chosen and an elementary structure-activity study was performed. The structure and energy properties were estimated by quantum-chemical semiempirical AM1 and molecular mechanics methods. The ionization constants pKα of the individual derivatives were calculated by program Pallas or estimated by potenciometric titration. The α 1 blocking activities were measured by rat thoracic aorta model. The experimental model used was not α 1 - adrenoreceptor subtypes specific, however, the α 1D subtype could be considered to be a predominant type in a rat aorta. The obtained physico-chemical parameters were then compared with the blocking activities of the derivatives and following determining characters for α 1 - adrenolytic activities were determined: 1) the polarity of the substituted phenol ring represented by a map of molecular electrostatic potential and 2) the hexahydro-pyridine nitrogen pKα constant, which represents the ability of the compound to be protonated by physiologic pH.
JavaScript is turned off in your web browser. Turn it on to take full advantage of this site, then refresh the page.