1141874-17-0Relevant articles and documents
Synthesis, structural characterisation, and preliminary evaluation of non-indolin-2-one-based angiogenesis inhibitors related to sunitinib (Sutent)
Sudta, Pichit,Kirk, Nicholas,Bezos, Anna,Gurlica, Anthony,Mitchell, Rhys,Weber, Thomas,Willis, Anthony C.,Prabpai, Samran,Kongsaeree, Palangpon,Parish, Christopher R.,Suksamrarn, Sunit,Kelso, Michael J.
, p. 864 - 873 (2013/09/12)
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.
