Abstract
Diphenyl ethers were demonstrated as a type of InhA inhibitors, which deactivate Fatty Acid Biosynthetic Pathway II in Mycobacterium tuberculosis and then block the synthesis of cell wall. Some small substituent groups at ortho position of B‐ring of diphenyl ethers introduce stronger binding affinity to InhA and special slow‐onset kinetic properties. A series of diphenyl ethers with different ortho groups on B‐ring were synthesized and tested for in vitro activity. All the compounds are tight binding inhibitors and showed good in vitro activity. The kinetics assay indicated that some compounds are slow‐onset inhibitors and that the sizes and charges of substituent groups affect kinetic properties. This work was supported by NIH Grant AI70383.
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