The author of 《Preclinical candidate for the treatment of visceral leishmaniasis that acts through proteasome inhibition》 were Wyllie, Susan; Brand, Stephen; Thomas, Michael; De Rycker, Manu; Chung, Chun-wa; Pena, Imanol; Bingham, Ryan P.; Bueren-Calabuig, Juan A.; Cantizani, Juan; Cebrian, David; Craggs, Peter D.; Ferguson, Liam; Goswami, Panchali; Hobrath, Judith; Howe, Jonathan; Jeacock, Laura; Ko, Eun-Jung; Korczynska, Justyna; MacLean, Lorna; Manthri, Sujatha; Martinez, Maria S.; Mata-Cantero, Lydia; Moniz, Sonia; NA1/4hs, Andrea; Osuna-Cabello, Maria; Pinto, Erika; Riley, Jennifer; Robinson, Sharon; Rowland, Paul; Simeons, Frederick R. C.; Shishikura, Yoko; Spinks, Daniel; Stojanovski, Laste; Thomas, John; Thompson, Stephen; Gaza, Elisabet Viayna; Wall, Richard J.; Zuccotto, Fabio; Horn, David; Ferguson, Michael A. J.; Fairlamb, Alan H.; Fiandor, Jose M.; Martin, Julio; Gray, David W.; Miles, Timothy J.; Gilbert, Ian H.; Read, Kevin D.; Marco, Maria; Wyatt, Paul G.. And the article was published in Proceedings of the National Academy of Sciences of the United States of America in 2019. Synthetic Route of C12H17BO2 The author mentioned the following in the article:
Visceral leishmaniasis (VL), caused by the protozoan parasites Leishmania donovani and Leishmania infantum, is one of the major parasitic diseases worldwide. There is an urgent need for new drugs to treat VL, because current therapies are unfit for purpose in a resource-poor setting. Here, we describe the development of a preclin. drug candidate, GSK3494245/DDD01305143/compound 8, with potential to treat this neglected tropical disease. The compound series was discovered by repurposing hits from a screen against the related parasite Trypanosoma cruzi. Subsequent optimization of the chem. series resulted in the development of a potent cidal compound with activity against a range of clin. relevant L. donovani and L. infantum isolates. Compound 8 demonstrates promising pharmacokinetic properties and impressive in vivo efficacy in our mouse model of infection comparable with those of the current oral antileishmanial miltefosine. Detailed mode of action studies confirm that this compound acts principally by inhibition of the chymotrypsin-like activity catalyzed by the β5 subunit of the L. donovani proteasome. High-resolution cryo-EM structures of apo and compound 8-bound Leishmania tarentolae 20S proteasome reveal a previously undiscovered inhibitor site that lies between the β4 and β5 proteasome subunits. This induced pocket exploits β4 residues that are divergent between humans and kinetoplastid parasites and is consistent with all of our exptl. and mutagenesis data. As a result of these comprehensive studies and due to a favorable developability and safety profile, compound 8 is being advanced toward human clin. trials. In the experiment, the researchers used 4,4,5,5-Tetramethyl-2-phenyl-1,3,2-dioxaborolane(cas: 24388-23-6Synthetic Route of C12H17BO2)
4,4,5,5-Tetramethyl-2-phenyl-1,3,2-dioxaborolane(cas: 24388-23-6) can be used to prepare sulfinamide derivatives by reacting with diethylaminosulfur trifluoride (DAST) and potassium phenyltrifluoroborate.Synthetic Route of C12H17BO2
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