3-Methoxy-2-phenylimidazo[1,2-b]pyridazines highly active against Mycobacterium tuberculosis and Mycobacterium marinum

3-Methoxy-2-phenylimidazo[1,2-b]pyridazines highly active against Mycobacterium tuberculosis and Mycobacterium marinum

A series of 3-methoxy-2-phenylimidazo[1,2-b]pyridazine derivatives which were highly active against autoluminescent Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm) in an in vitro assay were identified. SAR analysis showed that the most active compounds, which included a phenyl group...

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Veröffentlicht in:European journal of medicinal chemistry 2023-11, Vol.259, p.115637-115637, Article 115637
Hauptverfasser: Farrell, Kyle D., Gao, Yamin, Hughes, Deborah A., Henches, Robin, Tu, Zhengchao, Perkins, Michael V., Zhang, Tianyu, Francis, Craig L.
Format: Artikel
Sprache:eng
Schlagworte:
Antimycobacterial activity
Imidazo[1,2-b]pyridazine
Metabolism
Mycobacterium tuberculosis
Pharmacokinetic
SAR
Synthesis
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Zusammenfassung:A series of 3-methoxy-2-phenylimidazo[1,2-b]pyridazine derivatives which were highly active against autoluminescent Mycobacterium tuberculosis (Mtb) and Mycobacterium marinum (Mm) in an in vitro assay were identified. SAR analysis showed that the most active compounds, which included a phenyl group bearing fluoro substituent(s) at C2, a methoxy function at C3, and a benzyl-heteroatom moiety at C6, exhibited in vitro MIC90 values generally around 0.63–1.26 μM against Mtb and Mm. However, these compounds were inactive against Mtb in vivo (mice), and investigations revealed very short metabolic half-lives (
ISSN:0223-5234
1768-3254
DOI:10.1016/j.ejmech.2023.115637