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

被引：16

作者：

Krause-Heuer, Anwen M. ^{[1
]}

Howell, Nicholas R. ^{[1
]}

Matesic, Lidia ^{[1
]}

Dhand, Geetanjali ^{[1
]}

Young, Emma L. ^{[1
]}

Burgess, Leena ^{[1
]}

Jiang, Cathy D. ^{[1
]}

Lengkeek, Nigel A. ^{[1
]}

Fookes, Christopher J. R. ^{[1
]}

Pham, Tien Q. ^{[1
]}

Sobrio, Franck ^{[2
]}

Greguric, Ivan ^{[1
]}

Fraser, Benjamin H. ^{[1
]}

机构：

[1] Australian Nucl Sci & Technol Org, LifeSci Div, Kirrawee Dc, NSW 2232, Australia

[2] GIP Cyceron, CEA, LDM TEP, UMR ISTCT 6302,I2BM, F-14074 Caen, France

来源：

MEDCHEMCOMM | 2013年 / 4卷 / 02期

关键词：

SELECTIVE NONPEPTIDE INHIBITORS; AND-7; INHIBITORS; POTENT; SULFONAMIDE; MODULATION; ACTIVATION;

D O I：

10.1039/c2md20249b

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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' [F-18]-fluoride radiolabelling which proceeded in good yield and purity with no need for a protection/deprotection strategy.

引用

页码：347 / 352

页数：6

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