A new approach for the total synthesis of ammosamide B was realized. The strategy is based on an intermolecular Pd-catalyzed N-arylation of 4-chloro-1-methylindoline-2,3-dione (2), which enables construction of the key pyrroloquinoline skeleton precursor 6 within three steps in an overall yield of 80 %. The ammosamide B total synthesis is achieved in 12 simple transformations by starting from a commercially available starting material and proceeds with an overall yield of 23 %. Additionally, key precursor 6 represents an important intermediate in the synthesis of other pyrroloquinoline-containing natural products.

Tumor angiogenesis is mediated by vascular endothelial growth factor receptor (VEGFR) and other protein kinases. Inhibition of these kinases presents an attractive approach for developing anticancer therapeutics. In this work, a series of 2,5,7-trisubstituted oxazolo[5,4-d]pyrimidines were synthesized, and their inhibitory activities were investigated against VEGFR-2 and human umbilical vein endothelial cells (HUVEC) in vitro. Compound 9n exhibited the most potent inhibitory activity with IC₅₀ values of 0.33 and 0.29 μM for VEGFR-2 kinase and HUVEC, respectively. A further kinase selectivity assay revealed that these compounds exhibit good VEGFR and moderate EGFR inhibitory activities. Docking analysis suggested a common mode of interaction at the ATP-binding site of VEGFR-2.

A novel ligand-based pharmacophore model for KDR kinase was generated on the basis of chemical features of 30 KDR kinase inhibitors. This pharmacophore model consists of one hydrogen-bond acceptor, one hydrogen-bond donor and two hydrophobic groups. Several methods have been used to validate the model, suggesting that it can serve as a reliable tool for virtual screening to facilitate the discovery of novel KDR inhibitors. The model was then used as database search query from the National Cancer Institute (NCI) database for the rational design to identify new hit compound.