Labelling of the guanylate cyclase activator cinaciguat (BAY 58-2667) with carbon-14, tritium and stable isotopes
✍ Scribed by D. Seidel; U. Pleiß
- Publisher
- John Wiley and Sons
- Year
- 2010
- Tongue
- French
- Weight
- 218 KB
- Volume
- 53
- Category
- Article
- ISSN
- 0022-2135
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✦ Synopsis
Abstract
For studies of pharmacokinetics and drug metabolism of the new soluble guanylate cyclase activator cinaciguat (BAY 58‐2667) the ^14^C‐labelled compound was synthesized. The tritiated compound was required to elucidate the mode of action and the stable labelled compound was required for bio‐analytical studies by quantitative mass spectrometry as well. Two radiosyntheses are described with different formation of the labelled intermediate 1‐(chloro[^14^C]methyl)‐4‐(2‐phenylethyl)benzene. The first one started with ^14^C‐carboxylation of 1‐bromo‐4‐(2‐phenylethyl)benzene yielding the desired product in 5 steps. In the second synthesis intermediate 1‐(chloro[^14^C]methyl)‐4‐(2‐phenylethyl)benzene was formed by chloromethylation of bibenzyl with [^14^C]paraformaldehyde/hydrochloric acid subsequently resulting in the final product in three steps. Tritium labelling was performed by tritium exchange of the diester intermediate using an organo‐iridium catalyst and subsequent saponification. The stable labelled compound was synthesized via a convergent synthesis starting with ^13^C,^15^N‐cyanation of 1‐(chloromethyl)‐2‐{[4‐(2‐phenylethyl)benzyl]oxy}benzene and ^13^C‐cyanation of methyl 4‐bromobenzoate, respectively. The labelled product was obtained after 7 chemical steps. Copyright © 2010 John Wiley & Sons, Ltd.