Shanghai Haini Pharmaceutical Co. Ltd., Pudong District, Shanghai, PR China.
Bioorg Med Chem Lett. 2011 Jun 15;21(12):3578-82. doi: 10.1016/j.bmcl.2011.04.114. Epub 2011 May 3.
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.
新开发的单氟甲基化反应为各种具有有趣的单氟甲基单元的生物活性分子提供了途径。采用铱催化的不对称版本对广泛使用的非甾体抗炎药布洛芬（活性 S 异构体）进行了大规模的甲基单氟化。发现甲基单氟化的布洛芬选择性地抑制环加氧酶-1 而不是环加氧酶-2，令人惊讶的是，与母体药物布洛芬相比，该化合物具有几乎相同的药代动力学特征，在动物模型中显示出增加镇痛活性和减少胃损伤的作用。因此，甲基单氟化可能是改善“普芬”家族药物疗效和安全性的有效策略。
