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A new class of fluorinated 5-pyrrolidinylsulfonyl isatin caspase inhibitors for PET imaging of apoptosis

2012; Royal Society of Chemistry; Volume: 4; Issue: 2 Linguagem: Inglês

10.1039/c2md20249b

2040-2511

Anwen M. Krause‐Heuer, Nicholas Howell, Lidia Matesic, Geetanjali Dhand, Emma Young, Leena Burgess, Cathy D. Jiang, Nigel A. Lengkeek, Christopher J. R. Fookes, Tien Pham, Franck Sobrio, Ivan Greguric, Benjamin H. Fraser,

Metal complexes synthesis and properties

Thirteen compounds in a new class of fluorinated 5-pyrrolidinylsulfonyl isatin derivatives were synthesised that have potent and selective inhibitory activity against effector caspases-3 and -7. With in vivo animal PET imaging studies of cerebral ischemia being planned, N-benzylation with selected para-substituted benzylic halides allowed systematic variation of lipophilicity (logP 1.94–3.31) without decreasing inhibition potency (IC50). From this series the p-methoxybenzyl analogue was selected for initial 'proof-of-concept' [18F]-fluoride radiolabelling which proceeded in good yield and purity with no need for a protection/deprotection strategy.