Structure elucidation of a PDE5 inhibitor detected as an illegal adulteration in a libido-boosting dietary supplement

ABSTRACT

A compound with potent inhibitory activity for phosphodiesterase type 5 (PDE5) was identified as an illegal adulteration in a libido-boosting dietary supplement being sold at a store in Tokyo. This compound was identified as 5,6-diethyl-2-{5-[(4-methylpiperazin-1-yl)sulphonyl]-2-propoxyphenyl}pyrimidin-4(3H)-one using liquid chromatography-diode array detector (LC-DAD), liquid chromatography-tandem mass spectrometer (LC-MS), LC-HRMS, nuclear magnetic resonance (NMR), and X-ray crystallography. The IC₅₀ value of the inhibitory activity for PDE5A1 (one of the PDE5 isoforms) was 2.0 nM (sildenafil IC₅₀ value was 4.5 nM). This compound was previously synthesised as a PDE5 inhibitor by Shanghai Institute of Materia Medica. The dietary supplement contained 85 mg of this compound in a capsule, which was about 26% of the capsule content (320 mg).

Graphical abstract

KEYWORDS:

• Dietary supplements
• phosphodiesterase-5 inhibitor
• pyrimidenafil
• LC-MS
• NMR
• X-ray crystallography
• erectile dysfunction

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Correction

Acknowledgments

The authors thank Mr. Ikuo Suzuki for measuring the structure by X-ray crystallography and Junichi Nakajima for useful advice. This work was supported by the Pharmaceutical Affairs Section, the Tokyo Metropolitan Government, Tokyo, Japan.