TY - JOUR
T1 - Antiserotoninergic activity of 2‐aminoethylbenzocyclanones in rat aorta: Structure‐activity relationships
AU - Loza, M. I.
AU - G‐Ferreiro, T.
AU - Sanz, F.
AU - Lozoya, E.
AU - Rodriguez, J.
AU - Manaut, F.
AU - Verde, I.
AU - Castro, E.
AU - Fontenla, J. A.
AU - Cadavid, I.
AU - Honrubia, M.
AU - Fueyo, J.
AU - Raviña, E.
PY - 1993/1/1
Y1 - 1993/1/1
N2 - 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 ≤ pA2 ≤ 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. Copyright © 1993 Wiley‐Liss, Inc., A Wiley Company
AB - 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 ≤ pA2 ≤ 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. Copyright © 1993 Wiley‐Liss, Inc., A Wiley Company
U2 - 10.1002/jps.2600820516
DO - 10.1002/jps.2600820516
M3 - Article
SN - 0022-3549
VL - 82
SP - 513
EP - 517
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
IS - 5
ER -