Related Experiment Video
Updated: Feb 10, 2026

A Micropatterning Assay for Measuring Cell Chirality
Published on: March 11, 2022
Chiral analogues of (+)-cyclazosin as potent α1B-adrenoceptor selective antagonist
Gianni Sagratini1, Michela Buccioni1, Gabriella Marucci1
1Scuola in Scienze del Farmaco e dei Prodotti della Salute, Università di Camerino, Via S. Agostino 1, 62032 Camerino, Italy.
Abstract:
(+)-Cyclazosin [(+)-1] is one of most selective antagonists of the α1B-adrenoceptor subtype (selectivity ratios, α1B/α1A = 13, α1B/α1D = 38-39). To improve the selectivity, we synthesized and pharmacologically studied the blocking activity against α1-adrenoceptors of several homochiral analogues of (+)-cyclazosin featuring different substituents on the carbonyl or amine groups, namely (-)-2, (+)-3, (-)-4-(-)-8, (+)-9. Moreover, we studied the activity of some their opposite enantiomers, namely (-)-1, (-)-3, (+)-6, and (-)-9, to evaluate the influence of stereochemistry on selectivity. The benzyloxycarbonyl and methyl (4aS,8aR) analogues (+)-3 and (-)-6 improved in a significant way the α1B selectivity of the progenitor compound: 4 and 14 time vs. the α1D subtype and 35 and 77 times vs. the α1A subtype, respectively. The study confirmed the importance of the hydrophobic cis-octahydroquinoxaline moiety of these molecules for the establishment of interactions with the α1-adrenoceptors as well that of their (4aS,8aR) stereochemistry to grant selectivity for the α1B subtype. Hypotheses on the mode of interaction of these compounds were advanced on the basis of molecular modeling studies performed on compound (+)-3.
Related Concept Videos
Chirality
Chiral objects exhibit a sense of handedness when they interact with another chiral object. For example, our left foot can only fit in the left shoe and not in the right shoe. Achiral objects — objects that have...
Chirality in Nature
Adrenergic Receptors (Adrenoceptors): Classification
α-Adrenoceptors
α-Adrenoceptors are classified into two main subtypes: α1 and α2. The α1 adrenoceptors,...
Chirality at Nitrogen, Phosphorus, and Sulfur
A consequence of chirality is the need for enantiomeric resolution. While this is theoretically possible for all...
Molecules with Multiple Chiral Centers
Cholinergic Antagonists: Pharmacokinetics

