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Research paper thumbnail of Acides 2-naphtoïque substitués en tant qu'antagonistes de l'activité de gpr105

La presente invention concerne des acides 2-naphtoiques substitues representes par la formule str... more La presente invention concerne des acides 2-naphtoiques substitues representes par la formule structurelle (I) qui sont efficaces en tant qu'antagonistes de l'activite biologique de la proteine GPR105. Ils se revelent utiles pour le traitement, la regulation ou la prevention de troubles sensibles a l'antagonisme de ce recepteur, tels que le diabete, en particulier, le diabete de type 2, la resistance a l'insuline, l'hyperglycemie, les troubles lipidiques, l'obesite, l'atherosclerose, et des pathologies associees au syndrome metabolique.

Research paper thumbnail of Quinolinone as prostaglandin receptor ligand

Research paper thumbnail of Substituted 8-arylquinolune PDE4 inhibitors

Research paper thumbnail of Substituted 2-NAPHTHOIC Acids as Antagonists of GPR105 Activity

Research paper thumbnail of 2,3,5-TRISUBSTITUTED Pyridines as Inhibitors of CYCLOOXYGENASE-2

Research paper thumbnail of 2,3,5-TRISUBSTITUTED Pyridines as Inhibitors of CYCLOOXYGENASE-2

Research paper thumbnail of Azacycloalkane derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase

Research paper thumbnail of Substituted Pyridine Spleen Tyrosine Kinase (Syk) Inhibitors

Research paper thumbnail of Quinolinones as prostaglandin receptor ligands

Research paper thumbnail of Hetero-bridge substituted 8-arylquinoline pde4 inhibitors

Research paper thumbnail of Heteroaromatic compounds as inhibitors of stearoyl-coenzyme a delta-9 desaturase

Research paper thumbnail of Geometrical recognition ability of flexible bis-crown ether peptidic receptors

Journal of the Chemical Society, Chemical Communications, 1992

... Normand Voyer," Denis Deschenes, Julie Bernier, and Johanne Roby Department de chimie, U... more ... Normand Voyer," Denis Deschenes, Julie Bernier, and Johanne Roby Department de chimie, Universite de Sherbrooke, Quebec J7 K 2R 7, Canada ... demonstrates that the peptidic chain of receptors 1-3 plays a functional role and does not act like a passive linker between the ...

Research paper thumbnail of A novel bicyclic orthoester as a chiral auxiliary: Application to the synthesis of α-hydroxy acids

Tetrahedron Letters, 1995

Chiral ec-keto orthoesters derived from tartaric acid can be reduced diastereoselectively. Hydrol... more Chiral ec-keto orthoesters derived from tartaric acid can be reduced diastereoselectively. Hydrolysis affords optically active o~-hydroxy acids and the recovered auxiliary.

Research paper thumbnail of Design, synthesis, and supramolecular properties of bis-crown ether modified peptides

Supramolecular Chemistry, 1995

... NORMAND VOYER", JOHANNE ROBY, DENIS DESCHBNES and JULIE BERNIER ... binding ability note... more ... NORMAND VOYER", JOHANNE ROBY, DENIS DESCHBNES and JULIE BERNIER ... binding ability noted here supports the conclu-sions drawn with the metal ions that the peptidic chain of receptors 1-3 plays a functional role and does not act like a passive linker between the ...

Research paper thumbnail of Nitrogen-bridged substituted 8-arylquinolines as potent PDE IV inhibitors

Bioorganic & Medicinal Chemistry Letters, 2006

Potent inhibitors of the human PDE IV enzyme are described. Substituted 8-arylquinoline analogs b... more Potent inhibitors of the human PDE IV enzyme are described. Substituted 8-arylquinoline analogs bearing nitrogen-linked side chain were identified as potent inhibitors based on the SAR described herein. The pharmacokinetic profile of the best analog and the in vivo efficacy in an ovalbumin-induced bronchoconstriction assay in conscious guinea pigs are reported.

Research paper thumbnail of The discovery and synthesis of highly potent subtype selective phosphodiesterase 4D inhibitors

Bioorganic & Medicinal Chemistry Letters, 2010

The SAR study of a series of 6-aryloxymethyl-8-aryl substituted quinolines is described. Optimiza... more The SAR study of a series of 6-aryloxymethyl-8-aryl substituted quinolines is described. Optimization of the series led to the discovery of compound 26b, a highly potent (IC50=0.6 nM) and selective PDE4D inhibitor with a 75-fold selectivity over the A, B, and C subtypes and over 18,000-fold selectivity against other PDE family members. Rat pharmacokinetics and tissue distribution are also summarized.

Research paper thumbnail of Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: Structure–activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor

Bioorganic & Medicinal Chemistry Letters, 2005

The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein d... more The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC(50)<1nM) and also of LPS-induced TNF-alpha release in human whole blood…

Research paper thumbnail of Difluoroethylamines as an amide isostere in inhibitors of cathepsin K

Bioorganic & Medicinal Chemistry Letters, 2011

The trifluoroethylamine group found in cathepsin K inhibitors like odanacatib can be replaced by ... more The trifluoroethylamine group found in cathepsin K inhibitors like odanacatib can be replaced by a difluoroethylamine group. This change increased the basicity of the nitrogen which positively impacted the log D. This translated into an improved oral bioavailability in pre-clinical species. Difluoroethylamine compounds exhibit a similar potency against cathepsin K and selectivity profile against other cathepsins when compared to trifluoroethylamine analogs.

Research paper thumbnail of Alkyl-bridged substituted 8-arylquinolines as highly potent PDE IV inhibitors

Bioorganic & Medicinal Chemistry Letters, 2009

Substituted 8-arylquinoline analogs bearing alkyl-linked side chain were identified as potent inh... more Substituted 8-arylquinoline analogs bearing alkyl-linked side chain were identified as potent inhibitors of type 4 phophodiesterase. These compounds address the potential liabilities of the clinical candidate L-454560. The pharmacokinetic profile of the best analogs and the in vivo efficacy in an ovalbumin-induced bronchoconstriction assay in conscious guinea pigs are reported.

Research paper thumbnail of 2-Pyridinyl-3-(4-methylsulfonyl)phenylpyridines: Selective and orally active cyclooxygenase-2 inhibitors

Bioorganic & Medicinal Chemistry Letters, 1998

A series of novel 2-pyridinyl-3-(4-methylsulfonyl)phenylpyridines has been synthesized and evalua... more A series of novel 2-pyridinyl-3-(4-methylsulfonyl)phenylpyridines has been synthesized and evaluated with respect to their ability to inhibit the isozymes of cyclooxygenase, COX-l, and COX-2. Optimum COX-2 activity is observed by introduction of a substituent at C5 of the central pyridine. 5-Chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine 33 was identified as the optimum compound in this series.

Research paper thumbnail of Acides 2-naphtoïque substitués en tant qu'antagonistes de l'activité de gpr105

La presente invention concerne des acides 2-naphtoiques substitues representes par la formule str... more La presente invention concerne des acides 2-naphtoiques substitues representes par la formule structurelle (I) qui sont efficaces en tant qu'antagonistes de l'activite biologique de la proteine GPR105. Ils se revelent utiles pour le traitement, la regulation ou la prevention de troubles sensibles a l'antagonisme de ce recepteur, tels que le diabete, en particulier, le diabete de type 2, la resistance a l'insuline, l'hyperglycemie, les troubles lipidiques, l'obesite, l'atherosclerose, et des pathologies associees au syndrome metabolique.

Research paper thumbnail of Quinolinone as prostaglandin receptor ligand

Research paper thumbnail of Substituted 8-arylquinolune PDE4 inhibitors

Research paper thumbnail of Substituted 2-NAPHTHOIC Acids as Antagonists of GPR105 Activity

Research paper thumbnail of 2,3,5-TRISUBSTITUTED Pyridines as Inhibitors of CYCLOOXYGENASE-2

Research paper thumbnail of 2,3,5-TRISUBSTITUTED Pyridines as Inhibitors of CYCLOOXYGENASE-2

Research paper thumbnail of Azacycloalkane derivatives as inhibitors of stearoyl-coenzyme a delta-9 desaturase

Research paper thumbnail of Substituted Pyridine Spleen Tyrosine Kinase (Syk) Inhibitors

Research paper thumbnail of Quinolinones as prostaglandin receptor ligands

Research paper thumbnail of Hetero-bridge substituted 8-arylquinoline pde4 inhibitors

Research paper thumbnail of Heteroaromatic compounds as inhibitors of stearoyl-coenzyme a delta-9 desaturase

Research paper thumbnail of Geometrical recognition ability of flexible bis-crown ether peptidic receptors

Journal of the Chemical Society, Chemical Communications, 1992

... Normand Voyer," Denis Deschenes, Julie Bernier, and Johanne Roby Department de chimie, U... more ... Normand Voyer," Denis Deschenes, Julie Bernier, and Johanne Roby Department de chimie, Universite de Sherbrooke, Quebec J7 K 2R 7, Canada ... demonstrates that the peptidic chain of receptors 1-3 plays a functional role and does not act like a passive linker between the ...

Research paper thumbnail of A novel bicyclic orthoester as a chiral auxiliary: Application to the synthesis of α-hydroxy acids

Tetrahedron Letters, 1995

Chiral ec-keto orthoesters derived from tartaric acid can be reduced diastereoselectively. Hydrol... more Chiral ec-keto orthoesters derived from tartaric acid can be reduced diastereoselectively. Hydrolysis affords optically active o~-hydroxy acids and the recovered auxiliary.

Research paper thumbnail of Design, synthesis, and supramolecular properties of bis-crown ether modified peptides

Supramolecular Chemistry, 1995

... NORMAND VOYER", JOHANNE ROBY, DENIS DESCHBNES and JULIE BERNIER ... binding ability note... more ... NORMAND VOYER", JOHANNE ROBY, DENIS DESCHBNES and JULIE BERNIER ... binding ability noted here supports the conclu-sions drawn with the metal ions that the peptidic chain of receptors 1-3 plays a functional role and does not act like a passive linker between the ...

Research paper thumbnail of Nitrogen-bridged substituted 8-arylquinolines as potent PDE IV inhibitors

Bioorganic & Medicinal Chemistry Letters, 2006

Potent inhibitors of the human PDE IV enzyme are described. Substituted 8-arylquinoline analogs b... more Potent inhibitors of the human PDE IV enzyme are described. Substituted 8-arylquinoline analogs bearing nitrogen-linked side chain were identified as potent inhibitors based on the SAR described herein. The pharmacokinetic profile of the best analog and the in vivo efficacy in an ovalbumin-induced bronchoconstriction assay in conscious guinea pigs are reported.

Research paper thumbnail of The discovery and synthesis of highly potent subtype selective phosphodiesterase 4D inhibitors

Bioorganic & Medicinal Chemistry Letters, 2010

The SAR study of a series of 6-aryloxymethyl-8-aryl substituted quinolines is described. Optimiza... more The SAR study of a series of 6-aryloxymethyl-8-aryl substituted quinolines is described. Optimization of the series led to the discovery of compound 26b, a highly potent (IC50=0.6 nM) and selective PDE4D inhibitor with a 75-fold selectivity over the A, B, and C subtypes and over 18,000-fold selectivity against other PDE family members. Rat pharmacokinetics and tissue distribution are also summarized.

Research paper thumbnail of Discovery of a substituted 8-arylquinoline series of PDE4 inhibitors: Structure–activity relationship, optimization, and identification of a highly potent, well tolerated, PDE4 inhibitor

Bioorganic & Medicinal Chemistry Letters, 2005

The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein d... more The discovery and SAR of a new series of substituted 8-arylquinoline PDE4 inhibitors are herein described. This work has led to the identification of several compounds with excellent in vitro and in vivo profiles, including a good therapeutic window of emesis to efficacy in several animal models. Typical optimized compounds from this series are potent inhibitors of PDE4 (IC(50)<1nM) and also of LPS-induced TNF-alpha release in human whole blood…

Research paper thumbnail of Difluoroethylamines as an amide isostere in inhibitors of cathepsin K

Bioorganic & Medicinal Chemistry Letters, 2011

The trifluoroethylamine group found in cathepsin K inhibitors like odanacatib can be replaced by ... more The trifluoroethylamine group found in cathepsin K inhibitors like odanacatib can be replaced by a difluoroethylamine group. This change increased the basicity of the nitrogen which positively impacted the log D. This translated into an improved oral bioavailability in pre-clinical species. Difluoroethylamine compounds exhibit a similar potency against cathepsin K and selectivity profile against other cathepsins when compared to trifluoroethylamine analogs.

Research paper thumbnail of Alkyl-bridged substituted 8-arylquinolines as highly potent PDE IV inhibitors

Bioorganic & Medicinal Chemistry Letters, 2009

Substituted 8-arylquinoline analogs bearing alkyl-linked side chain were identified as potent inh... more Substituted 8-arylquinoline analogs bearing alkyl-linked side chain were identified as potent inhibitors of type 4 phophodiesterase. These compounds address the potential liabilities of the clinical candidate L-454560. The pharmacokinetic profile of the best analogs and the in vivo efficacy in an ovalbumin-induced bronchoconstriction assay in conscious guinea pigs are reported.

Research paper thumbnail of 2-Pyridinyl-3-(4-methylsulfonyl)phenylpyridines: Selective and orally active cyclooxygenase-2 inhibitors

Bioorganic & Medicinal Chemistry Letters, 1998

A series of novel 2-pyridinyl-3-(4-methylsulfonyl)phenylpyridines has been synthesized and evalua... more A series of novel 2-pyridinyl-3-(4-methylsulfonyl)phenylpyridines has been synthesized and evaluated with respect to their ability to inhibit the isozymes of cyclooxygenase, COX-l, and COX-2. Optimum COX-2 activity is observed by introduction of a substituent at C5 of the central pyridine. 5-Chloro-3-(4-methylsulfonyl)phenyl-2-(2-methyl-5-pyridinyl)pyridine 33 was identified as the optimum compound in this series.