Imidazoline ring proved to be an efficient and versatile basic function to obtain ligands interacting with different biological targets. Indeed, our previous studies provided molecules directed to I1- or I2-imidazoline binding sites, nicotinic or α2-adrenergic receptors. In all these molecules it is possible to recognize a common pharmacophore characterized by a lipophylic area (L) bound to the imidazoline ring through a bridge (X) (Chart 1A). Encouraged by the obtained results, in the present investigation we designed and prepared novel imidazoline molecules potentially targeting dopamine receptors (Chart 1B). The choice of the simultaneous or alternative insertion of hydroxyl groups in position 3 or 4 of the phenyl ring (portion L) was inspired by the presence of these functions in the aromatic area of dopamine and analogues. Similarly, the presence of N-benzyl or N-phenethyl pendant groups in efficacious dopaminergic ligands (1) suggested the N-substitution of the imidazoline ring. An ethylene or structurally related chain have been considered for the bridge (X). The synthesis of the novel compounds and preliminary pharmacological results will be described. (1) Zhang, A.; Neumeyer, J. L.; Baldessarini, R. J. J. Chem. Rev. 2007, 107, 274-302.

Design and synthesis of novel imidazoline derivatives potentially targeting dopamine receptors

DEL BELLO, FABIO;GIANNELLA, Mario;PIERGENTILI, Alessandro;QUAGLIA, Wilma
2012-01-01

Abstract

Imidazoline ring proved to be an efficient and versatile basic function to obtain ligands interacting with different biological targets. Indeed, our previous studies provided molecules directed to I1- or I2-imidazoline binding sites, nicotinic or α2-adrenergic receptors. In all these molecules it is possible to recognize a common pharmacophore characterized by a lipophylic area (L) bound to the imidazoline ring through a bridge (X) (Chart 1A). Encouraged by the obtained results, in the present investigation we designed and prepared novel imidazoline molecules potentially targeting dopamine receptors (Chart 1B). The choice of the simultaneous or alternative insertion of hydroxyl groups in position 3 or 4 of the phenyl ring (portion L) was inspired by the presence of these functions in the aromatic area of dopamine and analogues. Similarly, the presence of N-benzyl or N-phenethyl pendant groups in efficacious dopaminergic ligands (1) suggested the N-substitution of the imidazoline ring. An ethylene or structurally related chain have been considered for the bridge (X). The synthesis of the novel compounds and preliminary pharmacological results will be described. (1) Zhang, A.; Neumeyer, J. L.; Baldessarini, R. J. J. Chem. Rev. 2007, 107, 274-302.
2012
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11581/336583
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