3644-69-7Relevant articles and documents
Methyl sulfonamide substituents improve the pharmacokinetic properties of bicyclic 2-pyridone based: Chlamydia trachomatis inhibitors
Kulén, Martina,Nú?ez-Otero, Carlos,Cairns, Andrew G.,Silver, Jim,Lindgren, Anders E. G.,Wede, Emma,Singh, Pardeep,Vielfort, Katarina,Bahnan, Wael,Good, James A. D.,Svensson, Richard,Bergstr?m, Sven,Gylfe, ?sa,Almqvist, Fredrik
, p. 1966 - 1987 (2019/11/20)
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.
