synthesis and in vitro pharmacology of a series of histamine h2 ...

Corsano et al. 18
Chapter 2
have synthesized a series of hybrid molecules based on the calcium
channel blocker cinnarizine and the p rantagonist propranolol (fig. 14). Whereas
some of the hybrid molecules showed low affinity for atrial p adrenoceptors, none of
the designed hybrid molecules exhibited in vitro calcium channel blocking activity.
Figure 14: A hybrid molecule related to cinnarizine and propranolol
Laguerre et al. 19
have synthesized several hybrid molecules in which the calcium
channel blocker verapamil was combined with a- and p-adrenergic blocking
structural moieties and with cinnarizine type calcium channel blockers (fig. 15). Some
hybrid molecules with a p-adrenergic blocking moiety were nearly as potent as
verapamil in calcium channel blocking activity. The in vitro calcium channel blocking
activities (PIC50 values) determined on K +
-depolarization-induced contractions on
rabbit aorta ranged from 6.11-6.63. However, in vivo no increase in blood pressure
reduction was observed in spontaneously hypertensive rats. Besides, no adrenergic
blocking activities or affinities are presented. Therefore, it is impossible to confirm
whether these compounds can be considered as pharmacological relevant hybrid
molecules.
Willard et al. 20
have synthesized hybrid molecules based on a benzodioxane P-
adrenergic blocker and the diuretic quincarbate (fig. 16). However, the designed
tricyclic amino alcohols appeared to be inactive as a diuretic or as a p-adrenergic
blocker.
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