title: Discovery of (7-aryl-1,5-naphthyridin-2-yl)ureas as dual inhibitors of ERK2 and Aurora B kinases with antiproliferative activity against cancer cells.
abstract: A novel series of (7-aryl-1,5-naphthyridin-2-yl)ureas was discovered as dual ERK2 and Aurora B kinases inhibitors. Several analogues were active at micromolar and submicromolar range against ERK2 and Aurora B, associated with very promising antiproliferative activity toward various cancer cell lines. Synthesis, structure activity relationship and docking study are reported. In vitro ADME properties and safety data are also discussed.
authors.affiliation: Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer IICiMed EA 1155, UFR des Sciences Pharmaceutiques et Biologiques, 1 rue Gaston Veil, 44035 Nantes, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Defaux
authors.affiliation: Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer IICiMed EA 1155, UFR des Sciences Pharmaceutiques et Biologiques, 1 rue Gaston Veil, 44035 Nantes, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Antoine
authors.affiliation: Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer IICiMed EA 1155, UFR des Sciences Pharmaceutiques et Biologiques, 1 rue Gaston Veil, 44035 Nantes, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Logé
authors.affiliation: Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer IICiMed EA 1155, UFR des Sciences Pharmaceutiques et Biologiques, 1 rue Gaston Veil, 44035 Nantes, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Le Borgne
authors.affiliation: Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt/Main, Germany.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Schuster
authors.affiliation: Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt/Main, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Seipelt
authors.affiliation: Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt/Main, Germany.
authors.forename: Babette
authors.initials: B
authors.lastname: Aicher
authors.affiliation: Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt/Main, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Teifel
authors.affiliation: Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt/Main, Germany.
authors.forename: Eckhard
authors.initials: E
authors.lastname: Günther
authors.affiliation: Æterna Zentaris GmbH, Weismuellerstrasse 50, 60314 Frankfurt/Main, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gerlach
authors.affiliation: Université de Nantes, Nantes Atlantique Universités, Laboratoire de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer IICiMed EA 1155, UFR des Sciences Pharmaceutiques et Biologiques, 1 rue Gaston Veil, 44035 Nantes, France. Electronic address: pascal.marchand@univ-nantes.fr.
authors.forename: Pascal
authors.initials: P
authors.lastname: Marchand
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D064107:Aurora Kinase B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D014508:Urea; D064107:Aurora Kinase B; D019950:Mitogen-Activated Protein Kinase 1
keywords: 1,5-Naphthyridine; Antitumor activity; Aurora B; ERK2; Kinase inhibitor