The present invention relates to certain substituted AHR agonist compounds, to pharmaceutical compositions comprising the compounds and to methods of using the compounds to treat immune-mediated diseases.

The invention provides cereblon binders for the degradation of proteins by the ubiquitin proteasome pathway for therapeutic applications.

This invention provides amine-linked C.sup.3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.

This invention provides amine-linked C.sup.3-glutarimide Degronimers and Degrons for therapeutic applications as described further herein, and methods of use and compositions thereof as well as methods for their preparation.

This invention provides Degronimers that have carbon-linked E3 Ubiquitin Ligase targeting moieties (Degrons), which can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation.

This invention provides Degronimers that have carbon-linked E3 Ubiquitin Ligase targeting moieties (Degrons), which can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation.

A paroxetine intermediate, a method for preparing the same, and uses thereof are provided. Specifically, the method includes: reacting a compound of formula I below with a compound of formula II in the presence of air organic base under the catalysis of a complex formed from a chiral amine oxide L and a rare-earth metal compound Ln(OTf).sub.3 to prepare a compound of formula III below: wherein R.sub.1 is alkyl, phenyl or benzyl; R.sub.2, R.sub.3, R.sub.4 are each independently C.sub.1-C.sub.6 alkyl or C.sub.6-C.sub.10 aryl; the chiral amine oxide L has the following structure: wherein n=1, 2; and R=Ph-, 2,6-Me.sub.2C.sub.6H.sub.3-, 2,6-Et.sub.2C.sub.6H.sub.3-, 2,6-iPr.sub.2C.sub.6H.sub.3-, Ph.sub.2CH—.

##STR00001##

A paroxetine intermediate, a method for preparing the same, and uses thereof are provided. Specifically, the method includes: reacting a compound of formula I below with a compound of formula II in the presence of air organic base under the catalysis of a complex formed from a chiral amine oxide L and a rare-earth metal compound Ln(OTf).sub.3 to prepare a compound of formula III below: wherein R.sub.1 is alkyl, phenyl or benzyl; R.sub.2, R.sub.3, R.sub.4 are each independently C.sub.1-C.sub.6 alkyl or C.sub.6-C.sub.10 aryl; the chiral amine oxide L has the following structure: wherein n=1, 2; and R=Ph-, 2,6-Me.sub.2C.sub.6H.sub.3-, 2,6-Et.sub.2C.sub.6H.sub.3-, 2,6-iPr.sub.2C.sub.6H.sub.3-, Ph.sub.2CH—.

##STR00001##

The present disclosure provides compositions and methods for selectively killing senescent cells, wherein the composition comprises piperlongumine (PL) or derivative thereof. The selective killing of senescent cells may delay aging and/or treat age-related disorders.

The present disclosure provides compositions and methods for selectively killing senescent cells, wherein the composition comprises piperlongumine (PL) or derivative thereof. The selective killing of senescent cells may delay aging and/or treat age-related disorders.