title: Structure-activity relationships on adrenoceptors and imidazoline-preferring binding sites (I(1,2)-PBSs). Part 1: Weak intramolecular H-bond and conformational flexibility in a new I1-PBS-selective imidazoline analogue, trans1-(4',5'-dihydro-1'H-imidazol-2'-yl)methyl-2-hydroxyindane (PMS 952).
abstract: The highly selective I1-PBS imidazoline analogue PMS 952 has been selected to study the incidence of intramolecular hydrogen bond and molecular flexibility on its biological activity. On one hand, the weak energy difference between three calculated conformers does not support the stabilization of one conformer by an internal hydrogen bond. The 3-D electrostatic map confirms this feature and the solvent effect does not significantly modify the relative energy of these conformers. On the other hand, the conformational spaces of the neutral and ionized forms present a great number of equilibrium structures, in a short energetic range (20 Kcal). The results are representative of an exceptional conformational flexibility due to a cooperative effect between several parts of the molecule.
authors.affiliation: Laboratoire de Pharmacochimie Moléculaire et Systèmes Membranaires, Université Paris 7-Denis Diderot, France.
authors.forename: H F
authors.initials: HF
authors.lastname: Ye
authors.forename: G
authors.initials: G
authors.lastname: Dive
authors.forename: D
authors.initials: D
authors.lastname: Dehareng
authors.forename: F
authors.initials: F
authors.lastname: Heymans
authors.forename: J J
authors.initials: JJ
authors.lastname: Godfroid
mesh_terms: D000818:Animals; D001665:Binding Sites; D001923:Brain Chemistry; D002417:Cattle; D019281:Dimerization; D006860:Hydrogen Bonding; D007093:Imidazoles / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D054755:Imidazoline Receptors; D007668:Kidney / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D011817:Rabbits; D011869:Radioligand Assay; D011941:Receptors, Adrenergic / Q000737:chemistry / Q000378:metabolism*; D011955:Receptors, Drug / Q000737:chemistry / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: C418770:1-(4',5'-dihydro-1'H-imidazol-2'-yl)methyl-2-hydroxyindane; D007093:Imidazoles; D054755:Imidazoline Receptors; D011941:Receptors, Adrenergic; D011955:Receptors, Drug