Methyl-monofluorination of ibuprofen selectively increases its inhibitory activity toward cyclooxygenase-1 leading to enhanced analgesic activity and reduced gastric damage in vivo.

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Su H, Xie Y, Liu WB, You SL

Methyl-monofluorination of ibuprofen selectively increases its inhibitory activity toward cyclooxygenase-1 leading to enhanced analgesic activity and reduced gastric damage in vivo.

Bioorg Med Chem Lett. 2011 Jun 15;21(12):3578-82. doi: 10.1016/j.bmcl.2011.04.114. Epub 2011 May 3.

PubMed ID

21602044 [ View in PubMed

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Abstract

Newly developed monofluoromethylation reaction provided access to various bioactive molecules with an interesting monofluoromethyl unit. An iridium-catalyzed asymmetric version was employed for large-scale methyl-monofluorination of widely used nonsteroidal anti-inflammatory drug ibuprofen (the active S isoform). The methyl-monofluorinated ibuprofen was found to selectively inhibit cyclooxygenase-1 over cyclooxygenase-2 and surprisingly, the compound, with almost equal pharmacokinetic profile, was shown to increase analgesic activity and diminish gastric damage in animal models comparing to the parent drug ibuprofen. Therefore, methyl-monofluorination could be a useful strategy for improving efficacy and safety profile of drugs from the 'profen' family.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Ibuprofen	Prostaglandin G/H synthase 2	IC 50 (nM)	730	N/A	N/A	Details