Allosteric agonists of the calcium receptor (CaR): fluorine and SF5 analogues of cinacalcet

被引：25

作者：

Chia, Poh Wai ^{[1
,2
]}

Brennan, Sarah C. ^{[3
]}

Slawin, Alexandra M. Z. ^{[1
,2
]}

Riccardi, Daniela ^{[3
]}

O'Hagan, David ^{[1
,2
]}

机构：

[1] Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland

[2] Univ St Andrews, Ctr Biomol Sci, St Andrews KY16 9ST, Fife, Scotland

[3] Cardiff Univ, Cardiff CF10 3AX, S Glam, Wales

来源：

ORGANIC & BIOMOLECULAR CHEMISTRY | 2012年 / 10卷 / 39期

关键词：

SENSING RECEPTOR; C-F; BINDING; CONFORMATION; ENANTIOMERS; RESPONSES; ACIDS;

D O I：

10.1039/c2ob26402a

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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 SF5-cinacalcet analogue 4 was prepared from meta-pentafluorosulfanyl benzyl alcohol and has similar to 75% agonist activity relative to cinacalcet 1 indicating that the SF5 group can replace the CF3 group and retain significant bioactivity.

引用

页码：7922 / 7927

页数：6

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