Premium
Optimized palladium‐based approaches to analogues of PK 11195
Author(s) -
Guillou Sandrine,
Janin Yves L.
Publication year - 2008
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570450520
Subject(s) - chemistry , ferrocene , palladium , carboxylate , benzodiazepine , combinatorial chemistry , solubility , alkyl , gabaa receptor , receptor , stereochemistry , medicinal chemistry , organic chemistry , catalysis , biochemistry , electrode , electrochemistry
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).