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2006 | 1 | 4 | 370-378
Tytuł artykułu

The α 1-adrenolytic and structural evaluation of new pyridoindole derivatives

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Języki publikacji
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.

Opis fizyczny
  • Institute of Experimental Pharmacology, Slovak Academy of Sciences, 84104, Bratislava, Slovakia
  • Institute of Experimental Pharmacology, Slovak Academy of Sciences, 84104, Bratislava, Slovakia
  • Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Comenius University, 832 32, Bratislava, Slovakia
  • Department of Analytical Chemistry, Faculty of Chemical and Food Technology, Slovak Technical University, 81237, Bratislava, Slovakia
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