1020180-11-3

Upstream product

• 69321-60-4 2,6-dibromotoluene 
• 57260-71-6 1-t-Butoxycarbonylpiperazine 
• 97456-81-0 1-bromo-3-iodo-2-methylbenzene 

Relevant academic research and scientific papers

Discovery of G Protein-Biased D2 Dopamine Receptor Partial Agonists

Biased ligands (also known as functionally selective ligands) of G protein-coupled receptors are valuable tools for dissecting the roles of G protein-dependent and independent signaling pathways in health and disease. Biased ligands have also been increasingly pursued by the biomedical community as promising therapeutics with improved efficacy and reduced side effects compared with unbiased ligands. We previously discovered first-in-class β-arrestin-biased agonists of dopamine D2 receptor (D2R) by extensively exploring multiple regions of aripiprazole, a balanced D2R agonist. In our continuing efforts to identify biased agonists of D2R, we unexpectedly discovered a G protein-biased agonist of D2R, compound 1, which is the first G protein-biased D2R agonist from the aripiprazole scaffold. We designed and synthesized novel analogues to explore two regions of 1 and conducted structure-functional selectivity relationship (SFSR) studies. Here we report the discovery of 1, findings from our SFSR studies, and characterization of novel G protein-biased D2R agonists.

COMPOUNDS FOR TREATING PROSTATE CAN CANCER

A compound, or a pharmaceutically acceptable salt or ester thereof, having a formula I of: R20 - (Z)b - (Y)c - (R21)a - X - R22 - R23 wherein R20 is an aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a silyl-containing group, a boryl-containing group, a phosphine-containing group, amino, a thio-containing group, a seleno-containing group, halide, or a nitro- containing group; Z is alkanediyl, substituted alkanediyl, cycloalkanediyl, or substituted cycloalkanediyl; Y is S, O, or NR10, wherein R10 is H or alkyl; R21 is alkanediyl, substituted alkanediyl, cycloalkanediyl, substituted cycloalkanediyl, alkadienyl, substituted alkadienyl, alkatrienyl, substituted alkatrienyl; X is -C(=0)- or -S(=0)(=0)-; R22 is a moiety that includes at least one divalent amino radical; R23 is an aryl, substituted aryl, heteroaryl, substituted heteroaryl, heterocycloalkyl, substituted heterocycloalkyl, alkoxy, aryloxy, a silyl-containing group, a boryl-containing group, a phosphine- containing group, amino, a thio-containing group, a seleno-containing group, halide, or a nitro -containing group; a is 0 or 1; b is 0 or 1; and c is 0 or 1; provided that if X is -C(=0)- then Y is not S.

Palladium-catalyzed monoamination of dihalogenated benzenes

The palladium-catalyzed monoamination of symmetric dibromobenzenes can be performed using a catalyst based on Pd2dba3 and BINAP in the presence of NaO(t-Bu). The analogous transformation of non-symmetric bromoiodobenzenes is most effectively performed with Xantphos as the ligand, while reactions with BINAP were non-selective. These transformations can be scaled uneventfully to >10 g quantities. They do not require drybox or Schlenk techniques, and all reagents are weighed out in air. The resulting monobromoanilines are versatile intermediates for further synthetic transformations.