Document Report Card

ID: ALA2150905

Journal: ACS Med Chem Lett

Title: Discovery of Disubstituted Imidazo[4,5-b]pyridines and Purines as Potent TrkA Inhibitors.

Authors: Wang T, Lamb ML, Block MH, Davies AM, Han Y, Hoffmann E, Ioannidis S, Josey JA, Liu ZY, Lyne PD, MacIntyre T, Mohr PJ, Omer CA, Sjögren T, Thress K, Wang B, Wang H, Yu D, Zhang HJ.

Abstract: Trk receptor tyrosine kinases have been implicated in cancer and pain. A crystal structure of TrkA with AZ-23 (1a) was obtained, and scaffold hopping resulted in two 5/6-bicyclic series comprising either imidazo[4,5-b]pyridines or purines. Further optimization of these two fusion series led to compounds with subnanomolar potencies against TrkA kinase in cellular assays. Antitumor effects in a TrkA-driven mouse allograft model were demonstrated with compounds 2d and 3a.

CiteXplore: 24900538

DOI: 10.1021/ml300074j