Synthesis, conformation and antiproliferative activity of isothiazoloisoxazole 1,1-dioxides

• Published in: Organic & biomolecular chemistry Vol. 14; no. 6; p. 2134
• Main Authors: Blackburn, J, Molyneux, G, Pitard, A, Rice, C R, Page, M I, Afshinjavid, S, Javid, F A, Coles, S J, Horton, P N, Hemming, K
• Format: Journal Article
• Language: English
• Published: England 01-01-2016
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Proliferation - drug effects; Dose-Response Relationship, Drug; Drug Screening Assays, Antitumor; Humans; Isoxazoles - chemical synthesis; Isoxazoles - chemistry; Isoxazoles - pharmacology; MCF-7 Cells; Molecular Conformation; Structure-Activity Relationship; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology
• ISSN: 1477-0539
• DOI: 10.1039/c5ob02586a

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.