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Peer Reviewed
See detailDesign, synthèse et évaluation biologique de nouveaux dérivés coumariniques inhibiteurs de protéases à sérine
Schynts, M.; Jiang, K. Y.; Thierry, N. et al

Poster (1994, January 19)

Detailed reference viewed: 7 (0 ULg)
Peer Reviewed
See detailDesign, synthèse et évaluation pharmacologique de nouvelles 2-alkylamino-quinazoline-4-ones en tant du’isostères de 3-alkylamino-4H-pyrido[4,3-e]-1,2,4-thiadiazine 1,1-dioxydes
Somers, F.; Rogister, F.; Ouedraogo, R. et al

in Journal de Pharmacie de Belgique (1998), 53

Detailed reference viewed: 9 (0 ULg)
Peer Reviewed
See detailDesign, synthesis and anticancer activity of novel hydroxylated coumarin derivatives
Hemmer, Marc ULg; De Tullio, Pascal ULg; Bernard, Y. et al

Conference (2007, October)

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See detailDesign, Synthesis and Biological Activity of a Series of Torasemide Derivatives, Potent Blockers of the Na+ 2cl- K+ Co-Transporter: In-Vitro Study
Masereel, B.; Lohrmann, E.; Schynts, M. et al

in Journal of Pharmacy & Pharmacology (1992), 44

Pharmacomodulation of the torasemide molecule, a loop diuretic inhibiting Na+ 2Cl- K+ co-transport in the thick ascending limb of the loop of Henle has been performed in order to obtain new long-acting ... [more ▼]

Pharmacomodulation of the torasemide molecule, a loop diuretic inhibiting Na+ 2Cl- K+ co-transport in the thick ascending limb of the loop of Henle has been performed in order to obtain new long-acting diuretics. The aim of this study was to decrease the metabolism of the drug and to slow down its rate of excretion by increasing its hydrophobicity. The present study describes the synthesis and the inhibitory potency of new torasemide derivatives in the bioassay system of the cortical thick ascending limb of rabbit. A correlation between the lipophilicity (log P') of these substances and their activity as inhibitors of the Na+ Cl- K+ co-transporter was observed. The present design led to compounds more active than torasemide. Structure-activity relationships permit us to propose an interaction model between torasemide derivatives and the Na+ 2Cl- K+ co-transport system of the cortical thick ascending limb. [less ▲]

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See detailDesign, synthesis and biological evaluation of cognitive enhancers acting through the potentiation of the AMPA receptors
Francotte, Pierre ULg

Doctoral thesis (2008)

Alzheimer’s disease (AD) represents one of the greatest health problems in industrialized countries considering the ageing population. Only four drugs are currently approved for the treatment of this ... [more ▼]

Alzheimer’s disease (AD) represents one of the greatest health problems in industrialized countries considering the ageing population. Only four drugs are currently approved for the treatment of this disease. As these drugs are characterized with a limited time efficacy, it has become urgent to develop additional innovative AD treatments. Amongst the approaches that are actively investigated, the one consisting in potentiating a subclass of glutamate receptors appears attractive. This well advanced pharmacological approach includes three major classes of compounds amongst which appear the benzothiadiazine 1,1-dioxides. The present thesis is a pursuit of the preliminary efforts that were published in 1998 and 2001 by our team. Based on promising in vitro results obtained with the lead compound 59, pharmacomodulations around 59’s structure have been achieved in order to enhance its in vivo activity and to optimize its pharmacokinetic parameters. First efforts were devoted to exploratory synthesis where attention was paid to the impact of the substituent introduced at the 7-position. Moreover, some pyridothiadiazine dioxides as well as thienothiadiazine dioxides were prepared. The most important part of our pharmacomodulations was focused on the thiadiazine ring system. Considering that the poor in vivo results obtained with 59 could be due to a metabolic weakness of the latter, the introduction of fluorine atoms was tempted as a lead optimization strategy. This approach was successful, since it led to the synthesis of 95b which was selected for further pharmacological evaluations. This new lead compound was shown to exert significant cognitive-enhancing effects in vivo after oral administration to Wistar rats. Moreover, the study of the metabolic degradation of 95b allowed the assessment of the starting hypothesis that had dictated the pharmacomodulation’s philosophy. Finally, additional exploratory pharmacomodulations were achieved notably leading to the preparation of a quinazolinone series and 1,4-benzothiazine compounds. This research allowed to significantly improve the pharmacokinetic profile of our series and led to the identification of 95b as a new lead compound. However, many pharmacomodulations remain to be explored. The data collected during this thesis are appealing further studies. Efforts in the near future should lead to the design of novel drug candidates among which a future innovative AD treatment could emerge. [less ▲]

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Peer Reviewed
See detailDesign, synthesis and biological evaluation of sulfonylureas as original non-prostanoïd thromboxane A2 receptor antagonists
Dogne, J. M.; De Leval, X.; Damas, J. et al

Conference (1998, November 27)

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Peer Reviewed
See detailDesign, synthesis and biological evaluation of sulfonylureas as original non-prostanoid thromboxane A2 receptor antagonists
Dogne, J. M.; De Leval, X.; Damas, J. et al

Poster (1998, November 27)

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Peer Reviewed
See detailDesign, synthesis and biological evaluation of sulfonylureas as original non-prostanoid thromboxane receptor antagonists
Dogne, J. M.; Varache-Lembege, M.; Damas, J. et al

Conference (1997, April)

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Peer Reviewed
See detailDesign, synthesis and evaluation of graftable thrombin inhibitors for the preparation of blood-compatible polymer materials.
Salvagnini, Claudio; Michaux, Catherine; Remiche, Julie ULg et al

in Organic & Biomolecular Chemistry (2005), 3(23), 4209-20

Piperazinyl-amide derivatives of N-alpha-(3-trifluoromethyl-benzenesulfonyl)-L-arginine (1) were synthesized as graftable thrombin inhibitors. The possible disturbance of biological activity due to a ... [more ▼]

Piperazinyl-amide derivatives of N-alpha-(3-trifluoromethyl-benzenesulfonyl)-L-arginine (1) were synthesized as graftable thrombin inhibitors. The possible disturbance of biological activity due to a variable spacer-arm fixed on the N-4 piperazinyl position was evaluated in vitro, against human alpha-thrombin, and in blood coagulation assay. Molecular modelling (in silico analysis) and X-ray diffraction studies of thrombin-inhibitor complexes were also performed. The fixation of bioactive molecules on poly(butylene terephthalate) (PBT) and poly(ethylene terephthalate) (PET) membranes was performed by wet chemistry treatment and evaluated by XPS analysis. Surface grafting of inhibitor 1d improved the membrane hemocompatibility by reducing blood clot formation on the modified surface. [less ▲]

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See detailDesign, synthesis and pharmacological evaluation of dimeric ligands for the benzothiadiazine dioxide allosteric binding site of the AMPA receptors
Drapier, Thomas ULg; Francotte, Pierre ULg; Pirotte, Bernard ULg et al

Conference (2015, June 04)

L-glutamic acid is the major excitatory neurotransmitter in the brain. It exerts its effects through metabotropic and ionotropic receptors. Among the latter, three subtypes have been identified: NMDA ... [more ▼]

L-glutamic acid is the major excitatory neurotransmitter in the brain. It exerts its effects through metabotropic and ionotropic receptors. Among the latter, three subtypes have been identified: NMDA, AMPA and KA receptors. It is now well established that a deficit in glutamatergic signaling may be responsible for neurological disorders such as schizophrenia, depression, mild cognitive impairment and ADHD. Enhancement of the signal through positive allosteric modulators of AMPA receptors might be a therapeutic issue for these diseases. These compounds are expected to exert a fine tuning of the signal. Since they require the presence of the endogenous ligand to be active, they are expected to induce less toxicity than agonists. In this context, based on the structure of known allosteric modulators of AMPA receptors such as cyclothiazide (1) and IDRA 21 (2), the Laboratory of Medicinal Chemistry (University of Liège) has developed a series of 1,2,4-benzothiadiazine 1,1-dioxides with high potency as AMPA receptor potentiators, among which compounds (3) and (4). Crystallographic data obtained by the Department of Medicinal Chemistry (University of Copenhagen) highlighted that (3) and (4) bind to two contiguous sites at the dimer interface of the ligand binding domain of the AMPA receptor1,2. From these data, we may expect that the synthesis of dimeric molecules could lead to further improvement in affinity and activity. Our work consists in the development of a family of dimeric benzothiadiazine dioxides and their evaluation in a pharmacological assay. Several structural parameters such as the position of the bridge on the aromatic ring between the two heterocycles as well as its nature and length will be studied in order to determine their impact on the activity and thus the affinity. [less ▲]

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See detailDesign, synthesis and pharmacological evaluation of pyridinic analogues of nimesulide as cyclooxygenase-2 selective inhibitors
Julémont, F.; de Leval, X.; Michaux, C. et al

in Journal of Medicinal Chemistry (2004), 47

Detailed reference viewed: 18 (2 ULg)