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See detailTriphenylphosphonium salts of 1,2,4-benzothiadiazine 1,1-dioxides related to diazoxide targeting mitochondrial ATP-sensitive potassium channels
Constant-Urban, C.; Charif, M.; Goffin, Eric ULg et al

in Bioorganic & Medicinal Chemistry Letters (2013), 23

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See detailModerate chemical modifications of WAY-100635 improve the selectivity for 5-HT1A versus D4 receptors
Mangin, Floriane; Dilly, Sébastien ULg; Joly, Benoît ULg et al

in Bioorganic & Medicinal Chemistry Letters (2012)

The selectivity for 5-HT1A versus D4 receptors is significantly increased when the basic side chain of WAY-100635 is replaced by a 4-phenylpiperazine (3e) or a 4-phenyl-1,2,3,6-tetrahydropyridine moiety ... [more ▼]

The selectivity for 5-HT1A versus D4 receptors is significantly increased when the basic side chain of WAY-100635 is replaced by a 4-phenylpiperazine (3e) or a 4-phenyl-1,2,3,6-tetrahydropyridine moiety (3i). The 4-phenyl-1,2,3,6-tetrahydropyridine compounds (3i-l) have a higher affinity for 5-HT1A receptors than do the corresponding unsubstituted phenylpiperazine analogues (3e-h). Compounds 3e and 3i appear to be selective for 5-HT1A receptors over other relevant receptors and still behave as neutral antagonists. [less ▲]

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See detailSynthesis and radioligand binding studies of bis-(8-isopropylisoquinolinium) derivatives as ligands for apamin-sensitive sites on cloned SK2 and SK3 channels
Badarau, Eduard; Dilly, Sébastien ULg; Dufour, Fabien et al

in Bioorganic & Medicinal Chemistry Letters (2011), 21(22), 6756-6759

A structure-activity relationship study of N-methyl-laudanosine, a SK channel blocker, has indicated that the 6,7-dimethoxy group could be successfully replaced by a hydrophobic moiety such as an ... [more ▼]

A structure-activity relationship study of N-methyl-laudanosine, a SK channel blocker, has indicated that the 6,7-dimethoxy group could be successfully replaced by a hydrophobic moiety such as an isopropyl substituent in position 8 of the isoquinoline ring. In the present study, bis-(8-isopropyl-isoquinolinium) derivatives (2a-e) were synthesized and tested for their affinity for cloned SK2 and SK3 channels in comparison with their 6,7-dimethoxy analogues (4a-f). Several ligands were investigated, both in flexible (propyl, butyl and pentyl) and rigid (m- or p-xylyl) series, the m-xylyl derivative (2d) having the best profile in terms of affinity and selectivity for SK3/SK2 channels. Molecular studies showed that the optimal conformation of compound 2d fits well with our SK pharmacophore model. [less ▲]

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See detailMolecular modeling study of 4-phenylpiperazine and 4-phenyl-1,2,3,6-tetrahydropyridine derivatives: A new step towards the design of high-affinity 5-HT1A ligands
Dilly, Sébastien ULg; Graulich, Amaury; Liégeois, Jean-François ULg

in Bioorganic & Medicinal Chemistry Letters (2010), 20(2), 1118-1123

The main feature of many drugs having a 5-HT1A affinity is the presence of an arylpiperazine moiety. Indeed, the protonated nitrogen and the aromatic ring of the arylpiperazine compounds are considered ... [more ▼]

The main feature of many drugs having a 5-HT1A affinity is the presence of an arylpiperazine moiety. Indeed, the protonated nitrogen and the aromatic ring of the arylpiperazine compounds are considered crucial for the interaction with the receptor. However, the replacement of the piperazine moiety by a 1,2,3,6-tetrahydropyridine ring in 4-arylpiperazine-ethyl carboxamide derivatives was recently shown to be highly favourable for 5-HT1A affinity. In order to better understand the favourable effect of this chemical modification, we performed a conformational analysis of these compounds mainly based on the position of the phenyl ring relative to the piperazine and tetrahydropyridine moiety. In the piperazine compounds, the phenyl ring preferentially adopts a perpendicular orientation, whereas an almost planar orientation seems to be the most favourable conformation for the tetrahydropyridine compounds. Therefore, this conformational difference appears as a key for a better interaction with the receptor binding site. This result will serve for the designing high-affinity 5-HT1A ligands. [less ▲]

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See detailDiscovery of novel lipophilic inhibitors of OXA-10 enzyme (class D beta-lactamase) by screening amino analogs and homologs of citrate and isocitrate.
Beck, Joséphine; Vercheval, Lionel ULg; Bebrone, Carine ULg et al

in Bioorganic & Medicinal Chemistry Letters (2009), 19

Aminocitrate (and homolog) derivatives have been prepared by bis-alkylation of glycinate Schiff bases with bromoacetates (and ethyl acrylate), followed by N-acylation and esters (partial or complete ... [more ▼]

Aminocitrate (and homolog) derivatives have been prepared by bis-alkylation of glycinate Schiff bases with bromoacetates (and ethyl acrylate), followed by N-acylation and esters (partial or complete) deprotection. Aminoisocitrate was similarly obtained by mono-alkylation with diethyl fumarate. Evaluation against representative beta-lactamases revealed that the free acid derivatives are modest inhibitors of class A enzymes, whilst their benzyl esters showed a good inhibition of OXA-10 (class D enzyme). A docking experiment featured hydrophobic interactions in the active site. [less ▲]

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See detailSynthesis and pharmacological evaluation of a new targeted drug carrier system: β-Cyclodextrin coupled to oxytocin
Bertolla, C; Rolin, S; Evrard, Brigitte ULg et al

in Bioorganic & Medicinal Chemistry Letters (2008), 18

β-Cyclodextrin (β-CD) was monofunctionalized into its carboxylic derivative and then conjugated to the N-side of oxytocin (OT), a nonapeptide involved in human behavior and myometrium contraction. On ... [more ▼]

β-Cyclodextrin (β-CD) was monofunctionalized into its carboxylic derivative and then conjugated to the N-side of oxytocin (OT), a nonapeptide involved in human behavior and myometrium contraction. On isolated rat myometrium, this conjugate (β-CD-OT) partly preserves the contracting activity of OT (EC50 = 0.40 μM vs 1.7 nM). Moreover, the contraction induced frequency is also lowered by β-CD-OT. This novel hydrophilic targeted carrier could form a host–guest complex with prostaglandins and their derivatives used as labor inducers or with anticancer drugs used in cervix and endometrial cancer. This strategy can improve the solubility, the stability, and/or the biological activity of these drugs as well as reducing their side-effects. [less ▲]

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See detail2-Aminopropane-1,2,3-tricarboxylic acid: Synthesis and co-crystallization with the class A beta-lactamase BS3 of Bacillus licheniformis.
Beck, Josephine; Sauvage, Eric ULg; Charlier, Paulette ULg et al

in Bioorganic & Medicinal Chemistry Letters (2008), 18(13), 3764-8

The title compound 4 has been prepared in four steps from ethylglycinate in 63% overall yield. This amino analog of citric acid has been co-crystallized with the class A beta-lactamase BS3 of Bacillus ... [more ▼]

The title compound 4 has been prepared in four steps from ethylglycinate in 63% overall yield. This amino analog of citric acid has been co-crystallized with the class A beta-lactamase BS3 of Bacillus licheniformis and the structure of the complex fully analyzed by X-ray diffraction. Tris-ethyl aminocitrate 3 and the free tris-acid 4 have been tested against a member beta-lactamase from all distinct subgroups. They are novel inhibitors of class A beta-lactamases, still modest but more potent than citrate and isocitrate. [less ▲]

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See detailBis-tetrahydroisoquinoline derivatives: AG525E1, a new step in the search for non-quaternary non-peptidic small conductance Ca2+-activated K+ channel blockers
Graulich, Amaury ULg; Lamy, Cédric ULg; Alleva, Livia ULg et al

in Bioorganic & Medicinal Chemistry Letters (2008), 18(11), 3440-3445

So far, small conductance Ca2+-activated K+ channel (SK) blockers mostly consist of quaternary ammonium derivatives or peptides. Due to their physicochemical properties, these blockers are not suitable to ... [more ▼]

So far, small conductance Ca2+-activated K+ channel (SK) blockers mostly consist of quaternary ammonium derivatives or peptides. Due to their physicochemical properties, these blockers are not suitable to study the physiological roles of SK channels in the central nervous system in vivo. Herein, we report the discovery of a chiral bis-tertiary amine with SK blocking properties from chemical modulation of laudanosine. AG525E1 has an affinity for SK channels (K-i = 293 nM) approximately 100-fold higher than the tertiary compound laudanosine (K-i similar to 30 mu M) and similar to the charged compound dequalinium (K-i = 221 nM). AG525E1 equipotently blocks SK1, SK2 and SK3 currents in transfected cell lines. Because of its basic and lipophilic properties, it can reach central SK targets. (c) 2008 Elsevier Ltd. All rights reserved. [less ▲]

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See detailSynthesis and in vitro binding studies of substituted piperidine naphthamides. Part I: Influence of the substitution on the basic nitrogen and the position of the amide on the affinity for D-2L, D-4.2, and 5-HT2A receptors
Carato, P.; Graulich, Amaury ULg; Jensen, N. et al

in Bioorganic & Medicinal Chemistry Letters (2007), 17(6), 1565-1569

A series of 1- and 2-naphthamides has been prepared and tested for in vitro binding to D-2L, D-4.2, and 5-HT2A receptors. Different compounds display selectivity for D-4.2 and 5-HT2A receptors versus D-2L ... [more ▼]

A series of 1- and 2-naphthamides has been prepared and tested for in vitro binding to D-2L, D-4.2, and 5-HT2A receptors. Different compounds display selectivity for D-4.2 and 5-HT2A receptors versus D-2L receptors. N-(1-Arylalkyl-piperidin-4-yl) carboxamides have higher affinities than the corresponding N-(4-arylalkylamino-piperidin-1-yl) carboxamide analogues. A benzyl moiety in position 1 of the piperidine in the 2-naphthamide series (2) appears to be the best choice for a favorable interaction with D-4.2 and 5-HT2A receptors. Increasing the linker length between the phenyl ring and the basic nitrogen led to a decreased affinity for these receptors. In the 1-naphthamide series, the most potent D-4.2 ligand (7) possesses a phenylpropyl moiety while its affinity for 5-HT2A receptors is strongly reduced. All compounds with significant affinity for D-4.2 and 5-HT2A receptors were antagonists. (c) 2007 Elsevier Ltd. All rights reserved. [less ▲]

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See detailSynthesis and in vitro binding studies of substituted piperidine naphthamides. Part II: Influence of the substitution on the benzyl moiety on the affinity for D-2L, D-4.2, and 5-HT2A receptors
Carato, P.; Graulich, Amaury ULg; Jensen, N. et al

in Bioorganic & Medicinal Chemistry Letters (2007), 17(6), 1570-1574

In continuation of our work on N-(piperidin-4-yl)-naphthamides, the effect of substituted benzyl groups on D-2L, D-4.2, and 5-HT2A receptor affinity was evaluated. In the 1-naphthamide series most ... [more ▼]

In continuation of our work on N-(piperidin-4-yl)-naphthamides, the effect of substituted benzyl groups on D-2L, D-4.2, and 5-HT2A receptor affinity was evaluated. In the 1-naphthamide series most compounds were highly selective for D-4.2 over D-2L, and 5-HT2A receptors. Halogen and methyl substitution in position 3 or 4 of the benzyl group increased D-4.2 affinity. In the 2-naphthamide series a similar high D-4.2 over D-2L selectivity was retained while 5-HT2A affinity was increased. 3-Methoxy, 3-methyl, and 4-methyl substituents were favorable for D-4.2 affinity while halogens reduced affinity. 2-Naphthamides with a 3-bromo- or a 3-methyl group were mixed D-4.2/5-HT2A ligands similar to their unsubstituted parent compound. All compounds from both series with significant affinity for D-4.2 and 5-HT2A receptors were antagonists. (c) 2007 Elsevier Ltd. All rights reserved. [less ▲]

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See detailA minimalistic approach to identify substrate binding features in B1 Metallo-beta-lactamases
Poeylaut-Palena, Andres A; Tomatis, Pablo E; Karsisiotis, Andreas I et al

in Bioorganic & Medicinal Chemistry Letters (2007), 17(18), 5171-5174

The 2-oxoazetidinylacetate sodium salt was synthesized as a model of a minimal P-lactam drug. This compound and the monobactam aztreonam were assayed as substrates of the Metallo-p-lactamase Bell. None of ... [more ▼]

The 2-oxoazetidinylacetate sodium salt was synthesized as a model of a minimal P-lactam drug. This compound and the monobactam aztreonam were assayed as substrates of the Metallo-p-lactamase Bell. None of them was hydrolyzed by the enzyme. While the azetidinone was not able to bind Bell, aztreonam was shown to bind in a nonproductive mode. These results provide an explanation for the unability of Metallo-beta-lactamases to inactive monobactams and give some clues for inhibitor design. (c) 2007 Elsevier Ltd. All rights reserved. [less ▲]

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See detailStructural approach of the mechanism of inhibition of -chymotrypsin by coumarins
Wouters, J.; Huygens, M.; Pochet, L. et al

in Bioorganic & Medicinal Chemistry Letters (2002), 12

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See detailImidazolopyrazinones as potential antioxydants
Devillers, Ingrid; Dive, Georges ULg; De Tollenaere, Catherine et al

in Bioorganic & Medicinal Chemistry Letters (2001), 11(17), 2305-2309

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See detailNew gamma-lactam homologs of penems
Marchand-Brynaert, Jacqueline; Couplet, Blandine; Dive, Georges ULg et al

in Bioorganic & Medicinal Chemistry Letters (1993), 3(11), 2303-2308

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