[Show abstract][Hide abstract] ABSTRACT: A novel series of 4-[3,5-dioxo-11-oxa-4,9-diazatricyclo[18.104.22.168(2,6)]undec-4-yl]-2-trifluoromethyl-benzonitriles has been synthesized. The ability of these compounds to act as antagonists of the androgen receptor was investigated and several were found to have potent activity in vitro and in vivo.
[Show abstract][Hide abstract] ABSTRACT: Structure-activity relationships in a series of 4-[1H-indazol-5-ylamino]pyrrolo[2,1-f][1,2,4]triazine-6-carbamates identified dual human epidermal growth factor receptor (HER)1/HER2 kinase inhibitors with excellent biochemical potency and kinase selectivity. On the basis of its favorable pharmacokinetic profile and robust in vivo activity in HER1 and HER2 driven tumor models, 13 (BMS-599626) was selected as a clinical candidate for treatment of solid tumors.
Journal of Medicinal Chemistry 10/2009; 52(21):6527-30. · 5.61 Impact Factor