Design and Catalyzed Activation of Tak-242 Prodrugs for Localized Inhibition of TLR4-Induced Inflammation.
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ABSTRACT:
SUBMITTER: Plunk MA
PROVIDER: S-EPMC7025376 | biostudies-literature | 2020 Feb
REPOSITORIES: biostudies-literature
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Design and Catalyzed Activation of Tak-242 Prodrugs for Localized Inhibition of TLR4-Induced Inflammation.
Plunk Michael A MA Alaniz Alyssa A Olademehin Olatunde P OP Ellington Thomas L TL Shuford Kevin L KL Kane Robert R RR
ACS medicinal chemistry letters 20200103 2
Tak-242 (resatorvid), a Toll-like Receptor 4 (TLR4) inhibitor, has been identified as a potent suppressor of innate inflammation. As a strategy to target Tak-242 to select tissue, four TLR4-inactive prodrugs were synthesized for activation via two different release mechanisms. Two nitrobenzyl Tak-242 prodrugs released the parent drug upon exposure to the exogenous enzyme nitroreductase, while the two propargyl prodrugs were converted to Tak-242 in the presence of Pd<sup>0</sup>. ...[more]
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