gsk1322322 and Skin-Diseases--Infectious

gsk1322322 has been researched along with Skin-Diseases--Infectious* in 1 studies

Other Studies

1 other study(ies) available for gsk1322322 and Skin-Diseases--Infectious

Article	Year
Discovery of piperazic acid peptide deformylase inhibitors with in vivo activity for respiratory tract and skin infections. Bioorganic & medicinal chemistry letters, 2019, 08-15, Volume: 29, Issue:16 The discovery of a novel series of peptide deformylase inhibitors incorporating a piperazic acid amino acid found in nature is described. These compounds demonstrated potent in vitro enzymatic potency and antimicrobial activity. Crystal structure analysis revealed the piperazic acid optimized a key contact with the PDF protein that accounted for the increased enzymatic potency of these compounds. We describe lead optimization of the P3' region of the series that resulted in a compound with good potency against three target organisms. One molecule showed in vivo efficacy in a rat respiratory infection model but ultimately did not meet candidate progression criteria. Topics: Amidohydrolases; Anti-Bacterial Agents; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Discovery; Enzyme Inhibitors; Haemophilus influenzae; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Pyridazines; Respiratory Tract Infections; Skin Diseases, Infectious; Staphylococcus aureus; Streptococcus pneumoniae; Structure-Activity Relationship	2019

Article

Year

Discovery of piperazic acid peptide deformylase inhibitors with in vivo activity for respiratory tract and skin infections.

Bioorganic & medicinal chemistry letters, 2019, 08-15, Volume: 29, Issue:16

The discovery of a novel series of peptide deformylase inhibitors incorporating a piperazic acid amino acid found in nature is described. These compounds demonstrated potent in vitro enzymatic potency and antimicrobial activity. Crystal structure analysis revealed the piperazic acid optimized a key contact with the PDF protein that accounted for the increased enzymatic potency of these compounds. We describe lead optimization of the P3' region of the series that resulted in a compound with good potency against three target organisms. One molecule showed in vivo efficacy in a rat respiratory infection model but ultimately did not meet candidate progression criteria.

Topics: Amidohydrolases; Anti-Bacterial Agents; Crystallography, X-Ray; Dose-Response Relationship, Drug; Drug Discovery; Enzyme Inhibitors; Haemophilus influenzae; Microbial Sensitivity Tests; Models, Molecular; Molecular Structure; Pyridazines; Respiratory Tract Infections; Skin Diseases, Infectious; Staphylococcus aureus; Streptococcus pneumoniae; Structure-Activity Relationship

2019