Maddirala, Amarendar Reddy; Klein, Roger; Pinkner, Jerome S.; Kalas, Vasilios; Hultgren, Scott J.; Janetka, James W. published the artcile< Biphenyl Gal and GalNAc FmlH Lectin Antagonists of Uropathogenic E. coli (UPEC): Optimization through Iterative Rational Drug Design>, Related Products of 135999-16-5, the main research area is galactoside biphenyl preparation FmlH lectin antagonist UPEC urinary infection; galactosaminoside biphenyl preparation FmlH lectin antagonist UPEC urinary infection.
The F9/Yde/Fml pilus, tipped with the FmlH adhesin, has been shown to provide uropathogenic Escherichia coli (UPEC) a fitness advantage in urinary tract infections (UTIs). Here, the authors used X-ray structure guided design to optimize our previously described ortho-biphenyl Gal and GalNAc FmlH antagonists by replacing the carboxylate with a sulfonamide. Other groups which can accept H-bonds were also tolerated. The authors pursued further modifications to the biphenyl aglycon resulting in significantly improved activity. Two of the most potent compounds (IC50 = 0.051 μM) and (IC50 = 0.034 μM), exhibited excellent metabolic stability in mouse plasma and liver microsomes but showed only limited oral bioavailability (<1%) in rats. Another compound also showed a good pharmacokinetic (PK) profile in mice after IP dosing with compound exposure above the IC50 for 6 h. These new FmlH antagonists represent new antivirulence drugs for UTIs. Journal of Medicinal Chemistry published new progress about Drug design. 135999-16-5 belongs to class bromides-buliding-blocks, and the molecular formula is C7H7BrO2, Related Products of 135999-16-5.
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Bromide – Wikipedia,
bromide – Wiktionary