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.

Key words

Cinacalcet - calcimimetics - α-(monofluoromethyl)arylmethylamine - radiosynthesis - nucleophilic substitution

Publication History

Received: 08 September 2024

Accepted after revision: 16 October 2024

Article published online:
04 November 2024

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