Document Report Card

ID: ALA1212904

Journal: J Med Chem

Title: Discovery of pyrrole-indoline-2-ones as Aurora kinase inhibitors with a different inhibition profile.

Authors: Chiang CC, Lin YH, Lin SF, Lai CL, Liu C, Wei WY, Yang SC, Wang RW, Teng LW, Chuang SH, Chang JM, Yuan TT, Lee YS, Chen P, Chi WK, Yang JY, Huang HJ, Liao CB, Huang JJ.

Abstract: A series of pyrrole-indolin-2-ones were synthesized, and their inhibition profile for Aurora kinases was studied. The potent compound 33 with phenylsulfonamido at the C-5 position and a carboxyethyl group at the C-3' position selectively inhibited Aurora A over Aurora B with IC50 values of 12 and 156 nM, respectively. Replacement of the carboxyl group with an amino group led to compound 47, which retained the activity for Aurora B and lost activity for Aurora A (IC50=2.19 microM). Computation modeling was used to address the different inhibition profiles of 33 and 47. Compounds 47 and 36 (the ethyl ester analogue of 33) inhibited the proliferation of HCT-116 and HT-29 cells and suppressed levels of the phosphorylated substrates of Aurora A and Aurora B in the Western blots.

CiteXplore: 20681538

DOI: 10.1021/jm1001869