In this report, we disclose the design and synthesis of a series of pentafluorosulfanyl (SF₅) benzopyran derivatives as novel COX-2 inhibitors with improved pharmacokinetic and pharmacodynamic properties. The pentafluorosulfanyl compounds showed both potency and selectivity for COX-2 and demonstrated efficacy in several murine models of inflammation and pain. More interestingly, one of the compounds, R,S-3a, revealed exceptional efficacy in the adjuvant induced arthritis (AIA) model, achieving an ED₅₀ as low as 0.094 mg/kg. In addition, the pharmacokinetics of compound R,S-3a in rat revealed a half-life in excess of 12 h and plasma drug concentrations well above its IC₉₀ for up to 40 h. When R,S-3a was dosed just two times a week in the AIA model, efficacy was still maintained. Overall, drug R,S-3a and other analogues are suitable candidates that merit further investigation for the treatment of inflammation and pain as well as other diseases where COX-2 and PGE₂ play a role in their etiology.

中文翻译：

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五氟硫烷基取代的苯并吡喃类似物作为新的环氧合酶-2抑制剂，具有出色的药代动力学和阻断炎症的功效

在此报告中，我们公开了设计和合成一系列五氟硫烷基（SF ₅）苯并吡喃衍生物作为具有改善的药代动力学和药效特性的新型COX-2抑制剂。五氟硫烷基化合物对COX-2既有效价又有选择性，并且在几种小鼠炎症和疼痛模型中均显示出功效。更有趣的是，化合物R，S - 3a在佐剂诱导的关节炎（AIA）模型中显示出卓越的功效，ED ₅₀高达0.094 mg / kg。此外，化合物R，S - 3a的药代动力学大鼠的半衰期超过12小时，血浆药物浓度远高于其IC ₉₀长达40小时。在AIA模型中，每周仅两次给R，S - 3a给药时，疗效仍然得以维持。总体而言，药物R，S - 3a和其他类似物是合适的候选药物，值得进一步研究以治疗炎症和疼痛以及COX-2和PGE ₂在其病因中起作用的其他疾病。