Harmful:;124959-28-0Relevant articles and documents
Further hit optimization of 6-(trifluoromethyl)pyrimidin-2-amine based TLR8 modulators: Synthesis, biological evaluation and structure–activity relationships
Dol?ak, Ana,?ribar, Dora,Scheffler, Alexander,Grabowski, Maria,?vajger, Urban,Gobec, Stanislav,Holze, Janine,Weindl, Günther,Wolber, Gerhard,Sova, Matej
, (2021/09/06)
Toll-like receptor 8 (TLR8) is an endosomal TLR that has an important role in the innate human immune system, which is involved in numerous pathological conditions. Excessive activation of TLR8 can lead to inflammatory and autoimmune diseases, which highlights the need for development of TLR8 modulators. However, only a few small-molecule modulators that selectively target TLR8 have been developed. Here, we report the synthesis and systematic investigation of the structure–activity relationships of a series of novel TLR8 negative modulators based on previously reported 6-(trifluoromethyl)pyrimidin-2-amine derivatives. Four compounds showed low-micromolar concentration-dependent inhibition of TLR8-mediated signaling in HEK293 cells. These data confirm that the 6-trifluoromethyl group and two other substituents on positions 2 and 4 are important structural elements of pyrimidine-based TLR8 modulators. Substitution of the main scaffold at position 2 with a methylsulfonyl group or para hydroxy/hydroxymethyl substituted benzylamine is essential for potent negative modulation of TLR8. Our best-in-class TLR8-selective modulator 53 with IC50 value of 6.2 μM represents a promising small-molecule chemical probe for further optimization to a lead compound with potent immunomodulatory properties.
Palladium-catalyzed cross-couplings of lithium arylzincates with aromatic halides: Synthesis of analogues of isomeridianin G and evaluation as GSK-3β inhibitors
Seggio, Anne,Priem, Ghislaine,Chevallier, Floris,Mongin, Florence
experimental part, p. 3617 - 3632 (2010/03/05)
Several analogues of isomeridianin G have been synthesized using palladium-catalyzed cross-coupling reactions of lithium triorganozincates as a key step. The latter have been prepared by deprotonative lithiation followed by transmetalation using ZnCl
Inhibitors of Hepatitis C Virus
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Page/Page column 66, (2008/12/04)
Macrocyclic peptides are disclosed having the general formula: wherein R3, R3′, R4, R6, R′, X, Q and W are described. Compositions comprising the compounds and methods for using the compounds to inhibit HCV are also disclosed.
