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

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• 作者：Anna Minarini ; Gabriella Marucci ; Cristina Bellucci ; Gianluca Giorgi ; Vincenzo Tumiatti ; Maria Laura Bolognesi ; Riccardo Matera ; Michela Rosini ; Carlo Melchiorre
• 关键词：Pirenzepine ; Cyclohexanediamine ; Tripitramine ; Perhydroquinoxaline ; Muscarinic receptors
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：1 August 2008
• 年：2008
• 卷：16
• 期：15
• 页码：7311-7320
• 全文大小：378 K

文摘

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.