Design of new potent and selective secretory phospholipase A2 inhibitors. 6 - Synthesis, structure-activity relationships and molecular modelling of 1-substituted-4-[4,5-dihydro-1,2,4-(4H)-oxadiazol-5-one-3-yl(methyl)]-functionalized aryl piperazin/one/dione derivatives

in Bioorganic & Medicinal Chemistry (2010), 18

Part 13: Synthesis and biological evaluation of piperazine derivatives with dual anti-PAF and anti-HIV-1 or pure antiretroviral activity

in Bioorganic & Medicinal Chemistry (2006), 14(23), 8109-8125

HIV-1 infection of the brain and PAF neurotoxicity are implicated in AIDS dementia complex. We previously reported that a trisubstituted piperazine derivative is able to diminish both HIV-1 replication in ... [more ▼]

HIV-1 infection of the brain and PAF neurotoxicity are implicated in AIDS dementia complex. We previously reported that a trisubstituted piperazine derivative is able to diminish both HIV-1 replication in monocyte-derived macrophages and PAF-induced platelet aggregation. We report in this work new compounds obtained by modifying its piperazine substituents. The structure-activity relationship study shows that a better dual activity or even pure antiretroviral compounds can be obtained in this series. (c) 2006 Elsevier Ltd. All rights reserved. [less ▲]

Design and modeling of new platelet-activating factor antagonists.2. Synthesis and biological activity of 1,4-bis-(3',4',5'-trimethoxybenzoyl)-2-alkyl and 2-alkoxymethylpiperazines

in Journal of Lipid Mediators and Cell Signalling (1996), 15

Design and modeling of new PAF antagonists - 1,4-bis-(3',4',5'-trimethoxybenzoyl)-2-substituted carbonyloxymethyl piperazines

in Journal of Lipid Mediators and Cell Signalling (1994), 10(1-2), 153-154

Paf-Receptor. iii. Conformational and Electronic Properties of Paf-Like Agonists and Antagonists

in Biochimica et Biophysica Acta (1991), 1085(1), 91-105

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 ... [more ▼]

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. [less ▲]

PAF receptor and cache-oreilles effect. Simple PAF antagonists

in Lipids (1991), 26(12), 1167-1171

Paf-Receptor. 1. 'Cache-Oreilles' Effect of Selected High-Potency Platelet-Activating Factor (Paf) Antagonists

in Journal of Lipid Mediators (1989), 1(4, Jul-Aug), 201-15

Three-dimensional electrostatic maps were calculated for six potent antagonists of platelet-activating factor (PAF), the antagonists being selected for their apparent structural heterogeneity. The ... [more ▼]

Three-dimensional electrostatic maps were calculated for six potent antagonists of platelet-activating factor (PAF), the antagonists being selected for their apparent structural heterogeneity. The molecules examined were the compact Ginkgolides BN 52020, BN 52021 and BN 52022 (1, 2 and 3), the semi-rigid kadsurenone (4), a flexible synthetic dinor type C furanoid lignan L-652,731 (5a) and the triazolothienobenzodiazepine WEB 2086 (7). Calculation of the electrostatic potential generated around all the above molecules showed the existence of two wells of negative potential or 'cache-oreilles' (ear-muffs), i.e., the isocontours drawn at -10 kcal/mol, located at 180 degrees from each other and separated by a maximum distance of 22-27 A. Except for the synthetic dinor type C furanoid lignan (5a), the molecules also presented a moderate hydrophobic fragment, which constitutes a third point of interaction with the high-affinity binding site in rabbit and human platelets. The findings of the present study allow speculation that this high-affinity acceptor site may be a 'polarized cylinder' with a diameter of 10-12 A. [less ▲]