ArticleMedicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents2026
Discovery of 3-(N-phenylsulfamoyl)-L-phenylalanine derivatives as novel and orally available LAT1-selective inhibitors.
Article in Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
In this study, we discovered and optimized a novel series of L-type amino acid transporter 1 (LAT1)-selective inhibitors. Starting from compound 1, efforts to explore the structure-activity relationship and optimize selectivity over L-type amino acid transporter 2 (LAT2) revealed the importance of the orientation of the terminal aromatic ring and led to the highly potent and LAT1-selective 2-phenoxy-substituted compound 19. Pharmacokinetic studies of 19 demonstrated that it is orally bioavailable (10 mg/kg, p.o., mouse, AUC:2354 ng·h/mL). Further optimization of the aromatic ring improved its metabolic stability and resulted in highly LAT1-selective and orally bioavailable (10 mg/kg, p.o., mouse, AUC:3449 ng·h/mL) compound 26. This series of compounds should be useful for research on LAT1 inhibitors.
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