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

• DOI: 10.1039/c2md20249b
• Publication Date: 2012-11-12T18:03:34Z
• Authors: Anwen M. Krause-H...; Nicholas R. Howell; Lidia Matesic; Geetanjali Dhand; Emma L. Young; Leena Burgess; Cathy D. Jiang; Nigel A. Lengkeek; Christopher J. R....; Tien Q. Pham; Franck Sobrio; Ivan Greguric; Benjamin H. Fraser
• Keywords: Isatin; Lipophilicity; PET Imaging

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 -7. With vivo animal PET imaging studies cerebral ischemia being planned, N-benzylation with selected para-substituted benzylic halides allowed systematic variation lipophilicity (logP 1.94–3.31) without decreasing inhibition potency (IC50). From this series the p-methoxybenzyl analogue was for initial 'proof-of-concept' [18F]-fluoride radiolabelling which proceeded good yield purity no need protection/deprotection strategy.