Synthesis and preliminary biological evaluation of new derivatives of the marine alkaloid leucettamine B as kinase inhibitors.
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.
Debdab
Mansour
M
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.
Renault
Stéven
S
Lozach
Olivier
O
Meijer
Laurent
L
Paquin
Ludovic
L
Carreaux
François
F
Bazureau
Jean-Pierre
JP
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*
D000470:Alkaloids; D052117:Benzodioxoles; D048288:Imidazolines; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases