Optimized palladium-based approaches to analogues of PK 11195

Sandrine Guillou (1) , Yves L Janin (1)

1 Chimie Organique

The peripheral-type benzodiazepine receptor ligands such as PK 11195 and Ro 5-4864 were found more than twenty years ago in the course of research on neurobiology. These ligands were instrumental in pointing out an involvement of the peripheral-type benzodiazepine receptor (PBR) in apoptosis processes. With in mind an improvement of the solubility of PK 11195 in biological media, we report here improved reaction conditions for the palladium-based arylation reaction of alkyl 1-bromoisoquinoline-3-carboxylates and its ethyl 4-bromoquinoline-2-carboxylate isomer. The use of [1,1'-bis(diphenylphosphino) ferrocene] dichloropalladium as a precatalyst enabled a much improved preparation of an array of the 1-arylisoquinoline-3-carboxylates as well as 4-arylquinoline-3-carboxylates. This work should pave the way for the design of chemical probes aiming at the elucidation of the PBR biological role(s).

Domaines: Chimie organique; Chimie thérapeutique; Cancer

Sandrine Guillou, Yves L Janin. Optimized palladium-based approaches to analogues of PK 11195. Journal of Heterocyclic Chemistry, 2008, 45, pp.1377-1384. ⟨10.1002/jhet.5570450520⟩. ⟨pasteur-00315965⟩