RIS ID

82038

Publication Details

Sudta, P., Kirk, N., Bezos, A., Gurlica, A., Mitchell, R., Weber, T., Willis, A. C., Prabpai, S., Kongsaeree, P., Parish, C. R., Suksamrarn, S. & Kelso, M. J. (2013). Synthesis, structural characterisation, and preliminary evaluation of non-indolin-2-one-based angiogenesis inhibitors related to sunitinib (Sutent®). Australian Journal of Chemistry: an international journal for chemical science, 66 (8), 864-873.

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.

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Link to publisher version (DOI)

http://dx.doi.org/10.1071/CH13219