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

AM Krause-Heuer, NR Howell, L Matesic, G Dhand…

Index: Krause-Heuer, Anwen M.; Howell, Nicholas R.; Matesic, Lidia; Dhand, Geetanjali; Young, Emma L.; Burgess, Leena; Jiang, Cathy D.; Lengkeek, Nigel A.; Fookes, Christopher J. R.; Pham, Tien Q.; Sobrio, Franck; Greguric, Ivan; Fraser, Benjamin H. MedChemComm, 2013 , vol. 4, # 2 p. 347 - 352

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Citation Number: 7

Abstract

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 ...