The PI3K pathway is acknowledged as a major cell signaling axis. The SH2-containing inositol phosphatase SHIP plays a major role in this pathway, hydrolyzing the PI3K product PI(3,4,5)P<sub>3</sub>, which attenuates several different PI3K effector pathways. SHIP has therefore become a therapeutic target for the treatment of a number of disorders, including Graft vs. Host disease and cancer. Recent results have also shown that inhibition of SHIP promotes the expansion of some adult stem cell populations and to increases in blood cell production. Efforts towards finding new inhibitors of SHIP utilizing high-throughput screening lead to the discovery of two quinoline-based structures that showed significant inhibition of SHIP. Scalable syntheses of these inhibitors have been developed. Both routes demonstrate utility as reliable sequences for the stereoselective construction of the anti-1,2-aminoalcohol configuration commonly found in biologically active 4-substituted quinolines. The synthesis and preliminary biological evaluation of analogs of these structures will be presented along with a model for binding to the active site of SHIP.

Inhibition of the inositol phosphatase SHIP utilizing quinoline-based small molecules

249th National Meeting (2015)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.