Wnt-pathway inhibitors with selective activity against triple-negative breast cancer: From thienopyrimidine to quinazoline inhibitors.

The Wnt-pathway has a critical role in development and tissue homeostasis and has attracted increased attention to develop anticancer drugs due to its aberrant activation in many cancers. In this study, we identified a novel small molecule series with a thienopyrimidine scaffold acting as a downstream inhibitor of the β-catenin-dependent Wnt-pathway. This novel chemotype was investigated using Wnt-dependent triple-negative breast cancer (TNBC) cell lines.

Radical Deuteration with DO: Catalysis and Mechanistic Insights.

Selective incorporation of deuterium atoms into molecules is of high interest for labeling purposes and for optimizing properties of drug candidates. A mild and environmentally benign method for the deuteration of alkyl iodides via radical pathway using DO as source of deuterium has been developed. The reaction is initiated and mediated by triethylborane in the presence of dodecanethiol as a catalyst.

Effect of Brønsted acids on the thiophenol-mediated radical addition-translocation-cyclization process for the preparation of pyrrolidine derivatives.

A thiophenol-mediated method for the conversion of propargylamines to pyrrolidines under acidic conditions is described. This cascade reaction involves addition of a thiyl radical to the terminal alkyne followed by a 1,5-hydrogen transfer (radical translocation) and a rapid cyclization affording the pyrrolidine ring. Our studies reveal that complete protonation of the tertiary amine with 10 equivalents of trifluoroacetic acid avoids undesired hydrogen atom abstractions by the thiyl radicals.

Catechols as Sources of Hydrogen Atoms in Radical Deiodination and Related Reactions.

When used with trialkylboranes, catechol derivatives, which are low-cost and low toxicity, are valuable hydrogen atom donors for radical chain reactions involving alkyl iodides and related radical precursors. The system 4-tert-butylcatechol/triethylborane has been used to reduce a series of secondary and tertiary iodides, a xanthate, and a thiohydroxamate ester. Catechol derivatives are right in the optimal kinetic window for synthetic applications, as demonstrated by highly efficient radical cyclizations.