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2006 | 1 | 4 | 370-378

Article title

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


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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
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.










Physical description


1 - 12 - 2006
6 - 10 - 2006


  • Institute of Experimental Pharmacology, Slovak Academy of Sciences, 84104, Bratislava, Slovakia
  • 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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