Synthesis and physicochemical characterization of novel phenotypic probes targeting the nuclear factor-kappa B signaling pathway

• Paul M. Hershberger,
• Satyamaheshwar Peddibhotla,
• E. Hampton Sessions,
• Daniela B. Divlianska,
• Ricardo G. Correa,
• Anthony B. Pinkerton,
• John C. Reed and
• Gregory P. Roth

Beilstein J. Org. Chem. 2013, 9, 900–907, doi:10.3762/bjoc.9.103

• may allow for better fundamental understanding of this highly complex biochemical signaling network and could advance future therapeutic translation toward the clinical setting. Keywords: ML029; ML130; ML146; ML236; ML237; Introduction The Molecular Libraries Network was established in 2005 as an

• probe, including their general physicochemical and pharmacological properties, are summarized in this report. Results and Discussion Phenotypic screening for noncanonical NF-κB pathway selective inhibitors of IL-8 production in HEK 293, HEK 293T (ML029) and 697 pre-B cells (ML236 and ML237): Most

• conducted efficiently without purification of any intermediates. This enabled several analogues to be prepared in parallel, using mass-directed reverse-phase preparative HPLC to recover the pure isolates. The second related probe, ML237, (12) was synthesized as shown in Scheme 3 [12]. Commercially available