Structure-activity relationships on adrenoceptors and imidazoline-preferring binding sites (I-1,I-2-PBSs). Part 1: Weak intramolecular H-bond and conformational flexibility in a new I-1-PBS-selective imidazoline analogue, trans1-(4 ',5 '-dihydro-1 ' H-imidazol-2 '-yl)methyl-2-hydroxyindane (PMS 952)

The highly selective I-1-PBS imidazoline analogue PMS 952 has been selected to study the incidence of intramolecular hydrogen bond and molecular ilexi bility on its biological activity. On one hand, the weak energy difference between three calculated conformers does not support the stabilization of o ne conformer by an internal hydrogen bond. The 3-D electrostatic map confir ms this feature and the solvent effect does not significantly modify the re lative energy of these conformers. On the other hand, the conformational sp aces of the neutral and ionized forms present a great number of equilibrium structures, in a short energetic range (20 Kcal). The results are represen tative of an exceptional conformational flexibility due to a cooperative ef fect between several parts of the molecule. (C) 2000 Elsevier Science Ltd. All rights reserved.