Plunk Michael A, Alaniz Alyssa, Olademehin Olatunde P, Ellington Thomas L, Shuford Kevin L, Kane Robert R
Department of Chemistry and Biochemistry, Baylor University, Waco, Texas 76798, United States.
Institute of Biomedical Studies, Baylor University, Waco, Texas 76798, United States.
ACS Med Chem Lett. 2020 Jan 3;11(2):141-146. doi: 10.1021/acsmedchemlett.9b00518. eCollection 2020 Feb 13.
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.
Tak-242（瑞斯托维德）是一种Toll样受体4（TLR4）抑制剂，已被确定为先天性炎症的有效抑制剂。作为将Tak-242靶向特定组织的策略，合成了四种TLR4无活性前药，通过两种不同的释放机制进行激活。两种硝基苄基Tak-242前药在暴露于外源性酶硝基还原酶时释放母体药物，而两种炔丙基前药在钯存在下转化为Tak-242。
