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 I 1 -PBS-selective imidazoline analogue, trans 1-(4′,5′-dihydro-1′ H -imidazol-2′-yl)methyl-2-hydroxyindane (PMS 952)

Abstract

AbstractÐThe highly selective I 1 -PBS imidazoline analogue PMS 952 has been selected to study the incidence of intramolecular hydrogen bond and molecular ilexibility on its biological activity. On one hand, the weak energy dierence between three calculated conformers does not support the stabilization of one conformer by an internal hydrogen bond. The 3-D electrostatic map con®rms this feature and the solvent eect does not signi®cantly 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¯exibility due to a cooperative eect between several parts of the molecule. #

Synthesis and Biological Evaluation of New 2-(4,5-Dihydro-1H-imidazol-2-yl)-3,4-dihydro-2H-1,4-benzoxazine Derivatives

“…[32][33][34] Antiaggregatory effects of some N-(4,5-dihydro-1Himidazol-2-yl)indoles have been described. 35 Recently I 1 imidazoline binding site (I 1 BS) selective ligands PMS 952 36 and LNP 509 37 with hypotensive have been reported (Figure 1). Pigini also reported the synthesis of benazoline and tracizoline with high selectivity for I 1 BS over R 2 AR, but these ligands are devoid of hypotensive activity.…”