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Synthesis and pharmacological evaluation of imidazoline sites I1 and I2 selective ligands

2001; Elsevier BV; Volume: 9; Issue: 3 Linguagem: Inglês

10.1016/s0968-0896(00)00280-7

1464-3391

Maria Anastassiadou, Saı̈da Danoun, Louis Crane, G Baziard-Mouysset, M Payard, Daniel‐Henri Caignard, Marie‐Claire Rettori, Pierre Renard,

Synthesis of heterocyclic compounds

Several series of 2-aryl or heterocyclic-imidazoline compounds have been prepared and evaluated in vitro as imidazoline sites (I1 and I2) and α-adrenergic (α1 and α2) receptor ligands. Their pKi values indicate that linkage of the imidazoline moiety at the 2-position with an aromatic substituent dramatically decreases α-adrenergic affinity. I1 sites are more accessible by phenyl imidazolines substituted by a methyl or a methoxy group at the ortho or meta position. Indeed, 2-(2′-methoxyphenyl)-imidazoline (17) is one of the best I1 ligands ever reported (pKi=8.53 and I1/I2>3388). On the other hand, I2 selectivity increases in the presence of a methyl group in the para position. The original compound, 2-(3′-fluoro-4′-tolyl)-imidazoline (31) is a new potent ligand for the I2 sites with high selectivity (pKi=8.53 and I2/I1>3388).