title: Synthesis, conformation and antiproliferative activity of isothiazoloisoxazole 1,1-dioxides.
abstract: Sixteen new isothiazoloisoxazole 1,1-dioxides, one new isothiazolotriazole and one new isothiazolopyrazole have been synthesised by using 1,3-dipolar cycloadditions to isothiazole 1,1-dioxides. One sub-set of these isothiazoloisoxazoles showed low μM activity against a human breast carcinoma cell line, whilst a second sub-set plus the isothiazolotriazole demonstrated an interesting restricted rotation of sterically hindered bridgehead substituents. A thiazete 1,1-dioxide produced from one of the isothiazole 1,1-dioxides underwent conversion into an unknown 1,2,3-oxathiazolin-2-oxide upon treatment with Lewis acids, but was inert towards 1,3-dipoles and cyclopropenones. Six supporting crystal structures are included.
authors.affiliation: Department of Chemical Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK. k.hemming@hud.ac.uk.
authors.forename: J
authors.initials: J
authors.lastname: Blackburn
authors.affiliation: Department of Chemical Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK. k.hemming@hud.ac.uk.
authors.forename: G
authors.initials: G
authors.lastname: Molyneux
authors.affiliation: Department of Chemical Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK. k.hemming@hud.ac.uk.
authors.forename: A
authors.initials: A
authors.lastname: Pitard
authors.affiliation: Department of Chemical Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK. k.hemming@hud.ac.uk.
authors.forename: C R
authors.initials: CR
authors.lastname: Rice
authors.affiliation: Department of Chemical Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK. k.hemming@hud.ac.uk.
authors.forename: M I
authors.initials: MI
authors.lastname: Page
authors.affiliation: Faculty of Science & Engineering, Thornton Science Park, University of Chester, Chester, CH2 4NU, UK.
authors.forename: S
authors.initials: S
authors.lastname: Afshinjavid
authors.affiliation: Department of Pharmacy, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK.
authors.forename: F A
authors.initials: FA
authors.lastname: Javid
authors.affiliation: National Crystallography Service, School of Chemistry, University of Southampton, Southampton, SO17 1BJ, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Coles
authors.affiliation: National Crystallography Service, School of Chemistry, University of Southampton, Southampton, SO17 1BJ, UK.
authors.forename: P N
authors.initials: PN
authors.lastname: Horton
authors.affiliation: Department of Chemical Sciences, School of Applied Sciences, University of Huddersfield, Huddersfield, HD1 3DH, UK. k.hemming@hud.ac.uk.
authors.forename: K
authors.initials: K
authors.lastname: Hemming
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D061986:MCF-7 Cells; D008968:Molecular Conformation; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D007555:Isoxazoles; D013844:Thiazoles