Pirenzepine (2) is one of the most selective muscarinic M-1 versus M-2 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 M-1/M-2 selectivity of 2, due to an increased M-2 affinity. Rather, compounds 3-6 displayed a reversed selectivity showing more affinity at the muscarinic M-2 receptor than at all the other subtypes tested. (C) 2008 Elsevier Ltd. All rights reserved.
Minarini, A., Marucci, G., Bellucci, C., Giorgi, G., Tumiatti, V., Bolognesi, M.L., et al. (2008). Design, Synthesis, and Biological Evaluation of Pirenzepine Analogs Bearing a 1,2-Cyclohexanediamine and Perhydroquinoxaline Units in Exchange for the Piperazine Ring as Antimuscarinics. BIOORGANIC & MEDICINAL CHEMISTRY, 16(15), 7311-7320 [10.1016/j.bmc.2008.06.025].
Design, Synthesis, and Biological Evaluation of Pirenzepine Analogs Bearing a 1,2-Cyclohexanediamine and Perhydroquinoxaline Units in Exchange for the Piperazine Ring as Antimuscarinics
Giorgi, G.;
2008-01-01
Abstract
Pirenzepine (2) is one of the most selective muscarinic M-1 versus M-2 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 M-1/M-2 selectivity of 2, due to an increased M-2 affinity. Rather, compounds 3-6 displayed a reversed selectivity showing more affinity at the muscarinic M-2 receptor than at all the other subtypes tested. (C) 2008 Elsevier Ltd. All rights reserved.
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https://hdl.handle.net/11365/9918
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