A series of 2-methyl-5-nitrobenzenesulfonohydrazides were prepared and evaluated as inhibitors of PI3K. An isoquinoline derivative shows good selectivity for the p110alpha isoform over p110beta and p110delta, and also demonstrates good in vitro activity in a cell proliferation assay. Molecular modelling provides a rationalisation for the observed SAR.
Kendall, J., Rewcastle, G. W., Frederick, R., Mawson, C., Denny, W. A., Marshall, E. S., Baguley, B. C., Chaussade, C., Jackson, S., & Shepherd, P. R. (2007). Synthesis, biological evaluation and molecular modelling of sulfonohydrazides as selective PI3K p110alpha inhibitors. Bioorganic & Medicinal Chemistry, 15(24), 7677 - 7687. https://doi.org/10.1016/j.bmc.2007.08.062