Inhibitors of acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetylt ransferase (GlmU). Part 1: Hit to lead evaluation of a novel arylsulfonamide series.
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Green OM, McKenzie AR, Shapiro AB, Otterbein L, Ni H, Patten A, Stokes S, Albert R, Kawatkar S, Breed J
Inhibitors of acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetylt ransferase (GlmU). Part 1: Hit to lead evaluation of a novel arylsulfonamide series.
Bioorg Med Chem Lett. 2012 Feb 15;22(4):1510-9. doi: 10.1016/j.bmcl.2012.01.016. Epub 2012 Jan 14.
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- 22297115 [ View in PubMed]
- Abstract
A novel arylsulfonamide-containing series of compounds represented by 1, discovered by highthroughput screening, inhibit the acetyltransferase domain of N-acetylglucosamine-1-phosphate-uridyltransferase/glucosamine-1-phosphate-acetylt ransferase (GlmU). X-ray structure determination confirmed that inhibitor binds at the site occupied by acetyl-CoA, indicating that series is competitive with this substrate. This letter documents our early hit-to-lead evaluation of the chemical series and some of the findings that led to improvement in in-vitro potency against Gram-negative and Gram-positive bacterial isozymes, exemplified by compound 40.