title: Design of potent and selective GSK3beta inhibitors with acceptable safety profile and pharmacokinetics.
abstract: From potent and selective inhibitors of GSK3beta displaying CYP1A2 inhibition and poor PK properties, mostly linked to metabolic instability and in vivo hydrolysis of the amide bond, we were able to obtain safe and orally available inhibitors with good half lives.
authors.affiliation: Medicinal Chemistry, Sanofi-aventis, 13 Quai Jules Guesde, 94300 Vitry-sur-Seine, France. dominique.lesuisse@sanofi-aventis.com
authors.forename: Dominique
authors.initials: D
authors.lastname: Lesuisse
authors.forename: Gilles
authors.initials: G
authors.lastname: Tiraboschi
authors.forename: Alain
authors.initials: A
authors.lastname: Krick
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Abecassis
authors.forename: Gilles
authors.initials: G
authors.lastname: Dutruc-Rosset
authors.forename: Didier
authors.initials: D
authors.lastname: Babin
authors.forename: Frank
authors.initials: F
authors.lastname: Halley
authors.forename: Fabienne
authors.initials: F
authors.lastname: Châtreau
authors.forename: Sylvette
authors.initials: S
authors.lastname: Lachaud
authors.forename: Alain
authors.initials: A
authors.lastname: Chevalier
authors.forename: Dominique
authors.initials: D
authors.lastname: Quarteronet
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Burgevin
authors.forename: Céline
authors.initials: C
authors.lastname: Amara
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertrand
authors.forename: Thomas
authors.initials: T
authors.lastname: Rooney
mesh_terms: D000818:Animals; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D047428:Protein Kinase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*
chemical_list: D065609:Cytochrome P-450 CYP1A2 Inhibitors; D047428:Protein Kinase Inhibitors; D019388:Cytochrome P-450 CYP1A2; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; D038362:Glycogen Synthase Kinase 3