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- W3089226871 abstract "A series of 5,8-disubstituted tetrahydroisoquinolines were shown to be effective inhibitors of M. tb in culture and modest inhibitors of M. tb ATP synthase. There was a broad general trend of improved potency with higher lipophilicity. Large substituents (e.g., Bn) at the tetrahydroquinoline 5-position were well-tolerated, while N-methylpiperazine was the preferred 8-substituent. Structure-activity relationships for 7-linked side chains showed that the nature of the 7-linking group was important; -CO- and -COCH2- linkers were less effective than -CH2- or -CONH- ones. This suggests that the positioning of a terminal aromatic ring is important for target binding. Selected compounds showed much faster rates of microsomal clearance than did the clinical ATP synthase inhibitor bedaquiline, and modest inhibition of mycobacterial ATP synthase." @default.
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- W3089226871 date "2020-11-01" @default.
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- W3089226871 title "Synthesis and structure-activity relationships for tetrahydroisoquinoline-based inhibitors of Mycobacterium tuberculosis" @default.
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- W3089226871 doi "https://doi.org/10.1016/j.bmc.2020.115784" @default.
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