Allosteric agonists of the calcium receptor (CaR): fluorine and SF5 analogues of cinacalcetElectronic supplementary information (ESI) available: Experimental methods and crystallographic data. CCDC 892697. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c2ob26402a

• Main Authors: Chia, Poh Wai, Brennan, Sarah C, Slawin, Alexandra M. Z, Riccardi, Daniela, O'Hagan, David
• Format: Article
• Language: English
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c2ob26402a

Three selectively fluorinated cinacalcet analogues are prepared and their activity as calcium-sensing receptor (CaR) agonists is assessed. Individual (2 R ,1′ R )- 2 and (2 S ,1′ R )- 3 fluorocinacalcet diastereoisomers were prepared using the MacMillan asymmetric fluorination reaction. Assays with the recombinant human CaR revealed that both diastereoisomers have a similar potency to each other although slightly lower (75-80%) than that of cinacalcet 1 . The SF 5 -cinacalcet analogue 4 was prepared from meta -pentafluorosulfanyl benzyl alcohol and has ∼75% agonist activity relative to cinacalcet 1 indicating that the SF 5 group can replace the CF 3 group and retain significant bioactivity. The synthesis of three selectively fluorinated cinacalcet analogues have been prepared and their efficacy as calcium receptor (CaR) is determined.