Pirenzepine (2) is one of the most selective muscarinicM1 versus M2 receptor antagonists known. A series of 2 analogs, in which the piperazyl moiety was replaced by a cis- and trans-cyclohexane-1,2-diamine (3– 6) or a trans- and cis-perhydroquinoxaline rings (7 and 8) were prepared, with the aim to investigate the role of the piperazine ring of 2 in the interaction with the muscarinic receptors. The structural change leading to compounds 3–6 abolished in binding assays the muscarinic M1/M2 selectivity of 2, due to an increased M2 affinity. Rather, compounds 3–6 displayed a reversed selectivity showing more affinity at the muscarinic M2 receptor than at all the other subtypes tested.

Design, synthesis, and biological evaluation of pirenzepine analogs bearing a 1,2-cyclohexanediamine and a perhydroquinoxaline units in exchange for the piperazine ring as antimuscarinics

MINARINI, ANNA;TUMIATTI, VINCENZO;BOLOGNESI, MARIA LAURA;MATERA, RICCARDO;ROSINI, MICHELA;MELCHIORRE, CARLO
2008

Abstract

Pirenzepine (2) is one of the most selective muscarinicM1 versus M2 receptor antagonists known. A series of 2 analogs, in which the piperazyl moiety was replaced by a cis- and trans-cyclohexane-1,2-diamine (3– 6) or a trans- and cis-perhydroquinoxaline rings (7 and 8) were prepared, with the aim to investigate the role of the piperazine ring of 2 in the interaction with the muscarinic receptors. The structural change leading to compounds 3–6 abolished in binding assays the muscarinic M1/M2 selectivity of 2, due to an increased M2 affinity. Rather, compounds 3–6 displayed a reversed selectivity showing more affinity at the muscarinic M2 receptor than at all the other subtypes tested.
A. Minarini; G. Marucci; C. Bellucci; G. Giorgi; V. Tumiatti; M. L. Bolognesi; R. Matera; M. Rosini; C. Melchiorre
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11585/66196
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