The Synthesis and F-18 Labeling of a Cinacalcet Analogue Based on α-(Monofluoromethyl)arylmethylamine Structure

Abstract The fluorine-containing drug Cinacalcet is the only oral calcimimetic agent for the management of hyperparathyroidism in China and targets calcium sensitive receptor (CaSR) in organ tissues. The monofluoromethyl (CH2F) motif, found in many drug molecules and bioactive molecules, is particularly valuable as the CH2F functional group can mimic the methyl (CH3) motif frequently encountered in bioactive molecules. Replacing CH3 group of Cinacalcet with CH2F group will both bring new opportunities for the development of Cinacalcet generic drugs and provide a new option for the F-18 labeling synthesis of Cinacalcet. A Cinacalcet analogue has been successfully synthesized using commercial 2-amino-2-(naphthalen-1-yl)ethan-1-ol and 3-(3-(trifluoromethyl)phenyl)propanal as raw materials in a total yield of 24% in five steps and achieved the F-18 labeling synthesis of this analogue. This strategy is simple and efficient, paving the way for PET imaging of CaSR related diseases and inspiring development of new drugs based on Cinacalcet­.