title: Methyl-monofluorination of ibuprofen selectively increases its inhibitory activity toward cyclooxygenase-1 leading to enhanced analgesic activity and reduced gastric damage in vivo.
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.
authors: Shanghai Haini Pharmaceutical Co. Ltd., Pudong District, Shanghai, PR China.
authors: Hong
authors: H
authors: Su
authors: Yuli
authors: Y
authors: Xie
authors: Wen-Bo
authors: WB
authors: Liu
authors: Shu-Li
authors: SL
authors: You