title: Synthesis, biological evaluation and molecular modelling of sulfonohydrazides as selective PI3K p110alpha inhibitors.
abstract: 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.
authors.affiliation: Auckland Cancer Society Research Centre, School of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland 1020, New Zealand.
authors.forename: Jackie D
authors.initials: JD
authors.lastname: Kendall
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Rewcastle
authors.forename: Raphael
authors.initials: R
authors.lastname: Frederick
authors.forename: Claire
authors.initials: C
authors.lastname: Mawson
authors.forename: William A
authors.initials: WA
authors.lastname: Denny
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Marshall
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Baguley
authors.forename: Claire
authors.initials: C
authors.lastname: Chaussade
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Jackson
authors.forename: Peter R
authors.initials: PR
authors.lastname: Shepherd
mesh_terms: D000595:Amino Acid Sequence; D000730:Androstadienes / Q000494:pharmacology; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D004341:Drug Evaluation; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006834:Hydrazines / Q000737:chemistry* / Q000494:pharmacology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009025:Morpholines / Q000494:pharmacology; D009578:Nitrobenzenes / Q000737:chemistry* / Q000494:pharmacology; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D016415:Sequence Alignment; D013329:Structure-Activity Relationship; D000077191:Wortmannin
chemical_list: C526494:2-methyl-5-nitrobenzenesulfonohydrazide; D000730:Androstadienes; D002867:Chromones; D004791:Enzyme Inhibitors; D006834:Hydrazines; D009025:Morpholines; D009578:Nitrobenzenes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D000077191:Wortmannin