Synthesis of the calcilytic ligand NPS 2143.
(R)-3 (NPS 2143) is a negative allosteric modulator of the human calcium-sensing receptor (CaSR) and as such represents an important pharmacological tool compound for studying the CaSR. Herein, we disclose for the first time a complete experimental description, detailed characterisation and assessment of enantiomeric purity for (R)-3. An efficient, reproducible and scalable synthesis of (R)-3 that requires a minimum of chromatographic purification steps is presented. (R)-3 was obtained in excellent optical purity (er > 99:1) as demonstrated by chiral HPLC and the pharmacological profile for (R)-3 is in full accordance with that reported in the literature.
Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Henrik
H
Johansson
Thomas
T
Cailly
Alex
A
Rojas Bie Thomsen
Hans
H
Bräuner-Osborne
Daniel
D
Sejer Pedersen
GPCR; NPS 2143; epoxides; nucleophilic aromatic substitution; pyrylium chemistry