title: Structure-Activity Relationship of Azaindole-Based Glucokinase Activators.
abstract: 7-Azaindole has been identified as a novel bidentate anchor point for allosteric glucokinase activators. A systematic investigation around three principal parts of the new small molecule glucokinase activators led to a robust SAR in agreement with structural data that also helped to assess the conformational flexibility of the allosteric activation site. The increase in glucose uptake resulting from glucokinase activation in hepatocytes in vitro translated into the efficient lowering of glucose levels in vivo with the best compounds.
authors.affiliation: Servier Research Institute of Medicinal Chemistry , Záhony u. 7., H-1031 Budapest, Hungary.
authors.forename: Attila
authors.initials: A
authors.lastname: Paczal
authors.affiliation: Servier Research Institute of Medicinal Chemistry , Záhony u. 7., H-1031 Budapest, Hungary.
authors.forename: Balázs
authors.initials: B
authors.lastname: Bálint
authors.affiliation: Servier Research Institute of Medicinal Chemistry , Záhony u. 7., H-1031 Budapest, Hungary.
authors.forename: Csaba
authors.initials: C
authors.lastname: Wéber
authors.affiliation: Servier Research Institute of Medicinal Chemistry , Záhony u. 7., H-1031 Budapest, Hungary.
authors.forename: Zoltán B
authors.initials: ZB
authors.lastname: Szabó
authors.affiliation: Servier Research Institute of Medicinal Chemistry , Záhony u. 7., H-1031 Budapest, Hungary.
authors.forename: Levente
authors.initials: L
authors.lastname: Ondi
authors.affiliation: Institut de Recherches Servier , 92150 Suresnes, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Theret
authors.affiliation: Institut de Recherches Servier , 92150 Suresnes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: De Ceuninck
authors.affiliation: Institut de Recherches Servier , 92150 Suresnes, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Bernard
authors.affiliation: Institut de Recherches Servier , 92150 Suresnes, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Ktorza
authors.affiliation: Institut de Recherches Servier , 92150 Suresnes, France.
authors.forename: Francoise
authors.initials: F
authors.lastname: Perron-Sierra
authors.affiliation: Servier Research Institute of Medicinal Chemistry , Záhony u. 7., H-1031 Budapest, Hungary.
authors.forename: András
authors.initials: A
authors.lastname: Kotschy
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D020536:Enzyme Activators / Q000737:chemistry* / Q000494:pharmacology*; D005941:Glucokinase / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007211:Indoles / Q000737:chemistry* / Q000494:pharmacology*; D008958:Models, Molecular; D008968:Molecular Conformation; D061251:Primary Cell Culture; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: C023422:7-azaindole dimer; D020536:Enzyme Activators; D007004:Hypoglycemic Agents; D007211:Indoles; D005941:Glucokinase; D005947:Glucose