[en] In order to compare electronic and conformational properties of PAF-agonists and PAF-antagonists, 14 analogues structurally related to PAF were studied. A common conformation of the glycerol backbone was present in all agonists and all constrained or flexible antagonists. The distinction between agonists and antagonists appears to be casted on position-2 where the folded conformation of the substituent for agonists should be the most probable. In position-3 the gauche conformation can be adopted by all the analysed compounds. The electrostatic potential well at -30 kcal/mol stretches to the carbonyl group in position-2 in the folded conformation of the agonists. On the contrary, in constrained antagonists, a second negative zone appears around the carbamate group. Given the modelling results, the triethylammonium PAF analogue considered in literature as a weak agonist, was resynthesized and proved to be more potent than previously reported. These experimental results confirm our hypothesis in terms of a common conformation of agonist and antagonist PAF-like molecules.
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