Antiserotoninergic activity of 2-aminoethylbenzocyclanones in rat aorta: structure-activity relationships
| Autor: | María Isabel Loza, Ferran Sanz, I. Verde, Josep Rom Rodríguez, E. Castro, E. Raviña, J. Fueyo, M. Honrubia, Estrella Lozoya, José Angel Fontenla, F. Manaut, I. Cadavid, T. G-Ferreiro |
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| Rok vydání: | 1993 |
| Předmět: |
Steric effects
Serotonin Ketanserin Stereochemistry Molecular Conformation Pharmaceutical Science Aorta Thoracic In Vitro Techniques Muscle Smooth Vascular Rats Sprague-Dawley Structure-Activity Relationship Piperidines medicine Structure–activity relationship Moiety Animals 5-HT receptor Bicyclic molecule Chemistry Ketones Butyrophenones Planarity testing Rats Serotonin Antagonists medicine.drug Muscle Contraction |
| Zdroj: | Journal of pharmaceutical sciences. 82(5) |
| ISSN: | 0022-3549 |
| Popis: | The antiserotoninergic activity at the serotonin receptor subtype 2 (5-HT2) of seven new 2-aminoethylbenzocyclanones was determined with respect to serotonin-induced contractions in rat aorta and compared with that of ketanserine (pA2 = 8.87). Competitive antagonism was observed in six compounds (6.72 < or = pA2 < or = 8.12). Three-dimensional structures and molecular electrostatic potential distributions of ketanserine and 2-aminoethylbenzocyclanones were analyzed. Several molecular features correlated with the rank of antiserotoninergic activity. In the case of the cyclanone fragment, the rank of activity was associated with the degree of planarity of the bicyclic system. The steric and electrostatic effects due to the loss of planarity were analyzed. In the case of the amino moiety, activity was associated with a particular spatial pattern defined by the amino nitrogen, the aromatic system, and molecular electrostatic potential minima generated by the oxygen atom. |
| Databáze: | OpenAIRE |
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