Chlamydia trachomatis infections are a global health problem and new approaches to treat C. trachomatis with drugs of high specificity would be valuable. A library of substituted ring fused 2-pyridones has been synthesized and evaluated for their ability to attenuate C. trachomatis infectivity. In vivo pharmacokinetic studies were performed, with the best candidates demonstrating that a C8-methylsulfonamide substituent improved pharmacokinetic properties important for oral administration. C8-Methyl sulfonamide analogue 30 inhibited C. trachomatis infectivity in low micromolar concentrations. Further pharmacokinetic evaluation at an oral dose of 10 mg kg⁻¹ showed an apparent bioavailability of 41%, compared to C8-cyclopropyl and -methoxy analogues which had negligible oral uptake. In vitro ADME (absorption, distribution, metabolism and excretion) testing of solubility and Caco-2 cell permeability revealed that both solubility and permeability is greatly improved with the C8-methyl sulfonamide 30, effectively moving it from BCS (Biopharmaceutical Classification System) class IV to II.

中文翻译：

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甲基磺酰胺取代基改善了基于双环2-吡啶酮的沙眼衣原体抑制剂的药代动力学特性。

沙眼衣原体感染是一个全球性的健康问题，用高特异性药物治疗沙眼衣原体的新方法将是有价值的。已合成了取代的环稠合2-吡啶酮文库，并对其减弱沙眼衣原体感染力的能力进行了评估。进行了体内药代动力学研究，其中最佳候选者证明了C8-甲基磺酰胺取代基改善了对口服给药重要的药代动力学性质。C8-甲基磺酰胺类似物30在低微摩尔浓度下抑制沙眼衣原体感染。口服剂量为10 mg kg ^-1的进一步药代动力学评估与口服摄入量可忽略不计的C8-环丙基和-甲氧基类似物相比，表观生物利用度为41％。体外ADME（吸收，分布，代谢和排泄）溶解度和Caco-2细胞通透性测试表明，使用C8-甲基磺酰胺30可以大大提高溶解度和通透性，从而有效地使其脱离BCS（生物制药分类系统）IV级到II。