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 / A. Minarini; G. Marucci; C. Bellucci; G. Giorgi; V. Tumiatti; M. L. Bolognesi; R. Matera; M. Rosini; C. Melchiorre. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 16:(2008), pp. 7311-7320. [10.1016/j.bmc.2008.06.025]

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.
2008
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 / A. Minarini; G. Marucci; C. Bellucci; G. Giorgi; V. Tumiatti; M. L. Bolognesi; R. Matera; M. Rosini; C. Melchiorre. - In: BIOORGANIC & MEDICINAL CHEMISTRY. - ISSN 0968-0896. - STAMPA. - 16:(2008), pp. 7311-7320. [10.1016/j.bmc.2008.06.025]
A. Minarini; G. Marucci; C. Bellucci; G. Giorgi; V. Tumiatti; M. L. Bolognesi; R. Matera; M. Rosini; C. Melchiorre
File in questo prodotto:
Eventuali allegati, non sono esposti

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/11585/66196
 Attenzione

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

Citazioni
  • ???jsp.display-item.citation.pmc??? 0
  • Scopus 5
  • ???jsp.display-item.citation.isi??? 5
social impact