1022929-24-3

Upstream product

• 96042-30-7 4-(dicyanomethylene)-2-methyl-6-(p-dimethylaminostyryl)-4H-pyran 
• 403-33-8 methyl 4-flurobenzoate 
• 508234-07-9 ethyl 4-[4-(hydroxymethyl)-1-piperidyl]benzoate 

Downstream Products

• 1022929-26-5 C₁₉H₃₀N₂O₄ 

Relevant academic research and scientific papers

A CLASS OF BIFUNCTIONAL CHIMERIC HETEROCYCLIC COMPOUNDS FOR TARGETED DEGRADATION OF ANDROGEN RECEPTORS AND USE THEREOF

The present invention relates to a class of bifunctional chimeric heterocyclic compounds for targeted degradation of androgen receptors and use thereof, and specifically provides a compound of formula (I), or an isotopic compound thereof, or an optical isomer thereof, or a tautomer thereof, or a pharmacologically acceptable salt thereof, or a prodrug thereof, or a solvate thereof, wherein ARB is an androgen receptor recognition/binding part, L is a link part, and U is a ubiquitin protease recognition/binding part; and the three parts are connected by means of chemical bonds. The compound can perform the targeted degradation on androgen receptors in prostate cancer cells, and suppress the proliferation of the prostate cancer cells, and also show good metabolic stability and pharmacokinetic properties. The compound has good application prospect in the preparation of targeted chimeras for protein degradation of androgen receptors and in the preparation of drugs for treating the related diseases regulated by the androgen receptors.

ANDROGEN RECEPTOR PROTEIN DEGRADERS WITH A TRICYCLIC CEREBLON LIGAND

The present disclosure provides compounds represented by Formula I : A-L-B 1 I, and the salts or solvates thereof, wherein A, L, and B1 are as defined in the specification. ompounds having Formula I are androgen receptor degraders useful for the treatment of ancer and other diseases.

Strategies toward Discovery of Potent and Orally Bioavailable Proteolysis Targeting Chimera Degraders of Androgen Receptor for the Treatment of Prostate Cancer

Proteolysis targeting chimera (PROTAC) small-molecule degraders have emerged as a promising new type of therapeutic agents, but the design of PROTAC degraders with excellent oral pharmacokinetics is a major challenge. In this study, we present our strategies toward the discovery of highly potent PROTAC degraders of androgen receptor (AR) with excellent oral pharmacokinetics. Employing thalidomide to recruit cereblon/cullin 4A E3 ligase and through the rigidification of the linker, we discovered highly potent AR degraders with good oral pharmacokinetic properties in mice with ARD-2128 being the best compound. ARD-2128 achieves 67% oral bioavailability in mice, effectively reduces AR protein and suppresses AR-regulated genes in tumor tissues with oral administration, leading to the effective inhibition of tumor growth in mice without signs of toxicity. This study supports the development of an orally active PROTAC AR degrader for the treatment of prostate cancer and provides insights and guidance into the design of orally active PROTAC degraders.

COMPOUNDS AND METHODS FOR THE TARGETED DEGRADATION OF ANDROGEN RECEPTOR

This disclosure pertains to compounds, the preparation thereof, and the use of these compounds in the treatment of prostate cancer, including metastatic and/or castrate-resistant prostate cancer, in subjects in need thereof.

CEREBLON LIGANDS AND BIFUNCTIONAL COMPOUNDS COMPRISING THE SAME

The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and/or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation/inhibition of targeted polypeptides of nearly any type.

HYDROXAMATES AS INHIBITORS OF HISTONE DEACETYLASE

Compounds of formula (I), and salts, N-oxides, hydrates and solvates thereof are histone deacetylase inhibitors and are useful in the treatment of cell proliferative diseases, including cancers: wherein Q, V and W independently represent -N= or -C=; B is