In:
Future Medicinal Chemistry, Future Science Ltd, Vol. 1, No. 5 ( 2009-08), p. 969-989
Abstract:
Background: Dysregulation of type I programmed cell death (apoptosis) leads to a variety of diseases, among which cancer, cardiovascular and neurodegenerative disorders are the most prominent and widespread. Effector caspases such as caspases-3 and -7 get activated during the apoptotic signaling cascade and hence represent a biological target for the diagnosis and therapy of apoptosis-associated diseases. Methods: Synthesis of potent fluorinated analogs of the lead compound (S)-(+)-5-[1-(2-methoxymethylpyrrolidinyl)sulfonyl]isatin facilitates the aim-oriented identification of precursor candidates for 18 F-radiofluorination resulting in radiolabeled compounds that could be employed as tracers for the specific imaging of apoptosis in vivo, using positron-emission tomography. Conclusion: Within a series of new mono-, di- and trifluoromethylated pyrrolidine ring analogs of the lead compound, high inhibition potencies were found for caspases-3 and -7 with IC 50 values up to 30 and 37 nM, respectively. A new oxidative desulfurization–fluorination protocol was shown to be a versatile technique for fluorine incorporation.
Type of Medium:
Online Resource
ISSN:
1756-8919
,
1756-8927
Language:
English
Publisher:
Future Science Ltd
Publication Date:
2009
SSG:
15,3
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