Allosteric agonists of the calcium receptor (CaR): fluorine and SF sub(5) analogues of cinacalcet

Three selectively fluorinated cinacalcet analogues are prepared and their activity as calcium-sensing receptor (CaR) agonists is assessed. Individual (2R,1'R)-2 and (2S,1'R)-3 fluorocinacalcet diastereoisomers were prepared using the MacMillan asymmetric fluorination reaction. Assays with...

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Bibliographic Details
Published in:Organic & biomolecular chemistry 2012-09, Vol.10 (39), p.7922-7927
Main Authors: Chia, Poh Wai, Brennan, Sarah C, Slawin, Alexandra MZ, Riccardi, Daniela, O'Hagan, David
Format: Article
Language:English
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Summary:Three selectively fluorinated cinacalcet analogues are prepared and their activity as calcium-sensing receptor (CaR) agonists is assessed. Individual (2R,1'R)-2 and (2S,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 sub(5)-cinacalcet analogue 4 was prepared from meta-pentafluorosulfanyl benzyl alcohol and has similar to 75% agonist activity relative to cinacalcet 1 indicating that the SF sub(5) group can replace the CF sub(3) group and retain significant bioactivity.
ISSN:1477-0520
1477-0539
DOI:10.1039/c2ob26402a