title: Synthesis and biological evaluation of thienopyrrolizines, a new family of CDK/GSK-3 inhibitors.
abstract: Fifteen new thieno[2,3-b ]- and thieno[3,4-b]pyrrolizines were synthesized and tested against two protein kinases, CDK1/cyclin B and GSK-3. Among these compounds, 3-(3-hydroxy-4-methoxyphenyl)-8H-thieno[2,3-b]pyrrolizin-8-one 4g was identified as a moderate inhibitor of these kinases. Its molecular modeling study brought to the fore the pivotal role of the 2-methoxyphenol grouping and the interest in replacing it by bioisosteric moieties in future pharmacomodulations.
authors.affiliation: Centre d'Etudes et de Recherche sur le Medicament de Normandie, Université de Caen Basse Normandie, 14032 Caen cedex, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Rochais
authors.forename: Elodie
authors.initials: E
authors.lastname: Lescot
authors.forename: Vincent
authors.initials: V
authors.lastname: Lisowski
authors.forename: Alban
authors.initials: A
authors.lastname: Lepailleur
authors.forename: Jana Sopkova-de Oliveira
authors.initials: JS
authors.lastname: Santos
authors.forename: Ronan
authors.initials: R
authors.lastname: Bureau
authors.forename: Patrick
authors.initials: P
authors.lastname: Dallemagne
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.forename: Sylvain
authors.initials: S
authors.lastname: Rault
mesh_terms: D001665:Binding Sites / Q000187:drug effects; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D002453:Cell Cycle / Q000187:drug effects; D018360:Crystallography, X-Ray; D019926:Cyclin B / Q000037:antagonists & inhibitors; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D038362:Glycogen Synthase Kinase 3 / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D019926:Cyclin B; D004791:Enzyme Inhibitors; D011758:Pyrroles; D016203:CDC2 Protein Kinase; D038362:Glycogen Synthase Kinase 3