title: Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid leucettamine B as kinase inhibitors.
abstract: New derivatives of the marine alkaloid leucettamine B were prepared in five steps with overall yields ranging from 23 to 30%. The key step of our strategy has been the sulfur/nitrogen displacement under solvent-free microwave irradiation of (5Z) 5-benzo[1,3]-dioxo-5-ylmethylene-2-ethylsulfanyl-3,5-dihydroimidazol-4-one 3 with a mono-protected ethylenediamine 2. After deprotection of the N-Boc group, the amino derivative of leucettamine B 5 was subjected to reductive amination in two steps with retention of configuration of the double bond, to lead to eight new analogs of leucettamine B. The effect of these compounds on CK1alpha/beta, CDK5/p25, and GSK-3alpha/beta were investigated.
authors.affiliation: Université de Rennes 1, Sciences Chimiques de Rennes, UMR CNRS 6226, Groupe Ingénierie Chimique & Molécules pour le Vivant, Bât 10A, Campus de Beaulieu, Avenue du Général Leclerc, CS 74205, 35042 RENNES cedex, France.
authors.forename: Mansour
authors.initials: M
authors.lastname: Debdab
authors.forename: Stéven
authors.initials: S
authors.lastname: Renault
authors.forename: Olivier
authors.initials: O
authors.lastname: Lozach
authors.forename: Laurent
authors.initials: L
authors.lastname: Meijer
authors.forename: Ludovic
authors.initials: L
authors.lastname: Paquin
authors.forename: François
authors.initials: F
authors.lastname: Carreaux
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bazureau
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D052117:Benzodioxoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D048288:Imidazolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D009792:Oceans and Seas; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011494:Protein Kinases / Q000378:metabolism*
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D048288:Imidazolines; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases