Pirenzepine (2) is one of the most selective muscarinic M1 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 perhydroquinoxaline units in exchange for the piperazine ring as antimuscarinics

MARUCCI, Gabriella;
2008-01-01

Abstract

Pirenzepine (2) is one of the most selective muscarinic M1 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.
2008
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/112137
 Attenzione

Attenzione! I dati visualizzati non sono stati sottoposti a validazione da parte dell'ateneo

Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 5
  • ???jsp.display-item.citation.isi??? ND
social impact