Advances in tetrahydropyrido[1,2-a]isoindolone (valmerins) series: Potent glycogen synthase kinase 3 and cyclin dependent kinase 5 inhibitors.

International audienceAn efficient synthetic strategy was developed to modulate the structure of the tetrahydropyridine isoindolone (Valmerin) skeleton. A library of more than 30 novel final structures was generated. Biological activities on CDK5 and GSK3 as well as cellular effects on cancer cell lines were measured for each novel compound. Additionally docking studies were performed to support medicinal chemistry efforts. A strong GSK3/CDK5 dual inhibitor (38, IC50 GSK3/CDK5 32/84 nM) was obtained. A set of highly selective GSK3 inhibitors was synthesized by fine-tuning structural modifications (29 IC50 GSK3/CDK5 32/320 nM). Antiproliferative effects on cells were correlated with the in vitro kinase activities and the best effects were obtained with lung and colon cell lines

Allogeneic stem cell transplantation for patients with advanced rhabdomyosarcoma: A retrospective assessment

BACKGROUND: Allogeneic haematopoietic stem cell transplantation (allo-SCT) may provide donor cytotoxic T cell-/NK cell-mediated disease control in patients with rhabdomyosarcoma (RMS). However, little is known about the prevalence of graft-vs-RMS effects and only a few case experiences have been reported. METHODS: We evaluated allo-SCT outcomes of 30 European Group for Blood and Marrow Transplantation (EBMT)-registered patients with advanced RMS regarding toxicity, progression-free survival (PFS) and overall survival (OS) after allo-SCT. Twenty patients were conditioned with reduced intensity and ten with high-dose chemotherapy. Twenty-three patients were transplanted with HLA-matched and seven with HLA-mismatched grafts. Three patients additionally received donor lymphocyte infusions (DLIs). Median follow-up was 9 months. RESULTS: Three-year OS was 20% (s.e.±8%) with a median survival time of 12 months. Cumulative risk of progression was 67% (s.e.±10%) and 11% (s.e.±6%) for death of complications. Thirteen patients developed acute graft-vs-host disease (GvHD) and five developed chronic GvHD. Eighteen patients died of disease and four of complications. Eight patients survived in complete remission (CR) (median: 44 months). No patients with residual disease before allo-SCT were converted to CR. CONCLUSION: The use of allo-SCT in patients with advanced RMS is currently experimental. In a subset of patients, it may constitute a valuable approach for consolidating CR, but this needs to be validated in prospective trials

Couplage des methodes temporelle et frequentielle pour l'authentification du locuteur

SIGLECNRS T Bordereau / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Les sels d'onium à tâche spécifique (nouveaux supports (hydro-) solubles pour la synthèse organique)

Ce travail présente l'utilisation des liquides ioniques et de sels d'onium à tâche spécifique comme supports (hydro) solubles pour la synthèse organique supportée. après un préliminaire sur la synthèse organique supportée et un rappel sur la chimie des liquides ioniques, des sels d'onium à tâche spécifique ont été utilisés comme support soluble pour la réaction de baylis-hillman. Sont présentées ensuite la synthèse de sels d'onium à tâche spécifique et leur utilisation comme supports solubles en milieu aqueux, un acrylamide greffé sur un sel d'ammonium pour la réaction de michael et de heck et un aldéhyde supporté sur un chlorure d'ammonium pour la synthèse de tétrahydroquinoléines et de quinoléines ainsi que la réaction multi-composants de UGI. Au cours de ce travail, l accent est mis sur la possibilité de moduler les propriétés du sel d'onium à tâche spécifique en fonction des caractéristiques de stabilité et de solubilité souhaitées.RENNES1-BU Sciences Philo (352382102) / SudocSudocFranceF

Onium Salt Supported Organic Synthesis in Water: Application to Ugi's 4-Components Reaction

International audienc

Onium salt supported organic synthesis in water : application to Grieco's multicomponent reaction.

International audienc