Discovery of novel sphingosine kinase-1 inhibitors. Part 2

Working off the previously discovered sphingosine kinase-1 (SK1) inhibitor 4, structural optimization resulted in identification of a new series of analogs exemplified by compound 51 which have improved aqueous solubility and ADME properties while maintain or enhance enzyme potency. The lead 51 has also demonstrated modest oral bioavailability in a rat PK study.