Synthesis of 1-Alquilbenzodiazepinone as a Precursor of a Surface Active GABAA-R Ligand

GISELA J. QUINTEROS; ANAHÍ DEL V. TURINA; MARÍA A. PERILLO; ELIZABETH L. MOYANO

SAO PEDRO

Encuentro; 13th Brazilian Meeting on Organic Synthesis (BMOS); 2009

SOCIEDAD BRASILERA DE QUÍMICA

1,4-Benzodiazepin-2-ones (Bz) enhance the activity of the neurotransmitter GABA through an allosteric binding site at the integral membrane receptor GABAA-R. In order to study the GABAA-R closest membrane surroundings we proposed the design of a molecular probe consisting in a Bz-ligand containing a hydrophobic tail with a sensor moiety (fluorescent or spin label). Here we present the synthesis of a precursor of this ligand, Bz 3 from clonazepam (1) and 1,12 dibromododecane (2). Conventional and microwave synthetic methodologies were employed to obtain the target compound. In addition, NMR studies, GABAA-R binding kinetics, and biophysical properties of this new Bz-derivative are described.