Publication: Synthesis, structural characterisation, and preliminary evaluation of non-indolin-2-one-based angiogenesis inhibitors related to sunitinib (Sutent®)
Issued Date
2013-08-27
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ISSN
14450038
00049425
00049425
DOI
Other identifier(s)
2-s2.0-84882683064
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Mahidol University
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SCOPUS
Bibliographic Citation
Australian Journal of Chemistry. Vol.66, No.8 (2013), 864-873
Suggested Citation
Pichit Sudta, Nicholas Kirk, Anna Bezos, Anthony Gurlica, Rhys Mitchell, Thomas Weber, Anthony C. Willis, Samran Prabpai, Palangpon Kongsaeree, Christopher R. Parish, Sunit Suksamrarn, Michael J. Kelso Synthesis, structural characterisation, and preliminary evaluation of non-indolin-2-one-based angiogenesis inhibitors related to sunitinib (Sutent®). Australian Journal of Chemistry. Vol.66, No.8 (2013), 864-873. doi:10.1071/CH13219 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/31517
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Title
Synthesis, structural characterisation, and preliminary evaluation of non-indolin-2-one-based angiogenesis inhibitors related to sunitinib (Sutent®)
Abstract
The indolin-2-one fused-ring system and the 2,4-dimethylpyrrole unit represent key structural motifs in the anticancer drug sunitinib (Sutent®) and predecessor angiogenesis inhibitors that have undergone anticancer clinical trials (e.g. semaxanib, SU5416). In pursuit of novel anti-angiogenic scaffolds, we were interested in identifying whether the indolin-2-one group in these structures could be modified without losing activity. This paper describes novel condensation chemistry used to prepare a test series of (E)-and (Z)-alkenes related to SU5416 that retain the 2,4-dimethylpyrrole unit while incorporating ring-opened indolin-2-ones. Unique structural characteristics were identified in the compounds, such as intramolecular hydrogen bonds in the (Z)-alkenes, and several examples were shown to possess significant anti-angiogenic activity in a rat aorta in vitro model of angiogenesis. The work demonstrates that the indolin-2-one moiety is not an absolute requirement for angiogenesis inhibition in the sunitinib/SU5416 class. © 2013 CSIRO.