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Merck
  • Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays.

Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays.

Journal of medicinal chemistry (2004-12-24)
Louis J Lombardo, Francis Y Lee, Ping Chen, Derek Norris, Joel C Barrish, Kamelia Behnia, Stephen Castaneda, Lyndon A M Cornelius, Jagabandhu Das, Arthur M Doweyko, Craig Fairchild, John T Hunt, Ivan Inigo, Kathy Johnston, Amrita Kamath, David Kan, Herbert Klei, Punit Marathe, Suhong Pang, Russell Peterson, Sidney Pitt, Gary L Schieven, Robert J Schmidt, John Tokarski, Mei-Li Wen, John Wityak, Robert M Borzilleri
PMID15615512
ABSTRACT

A series of substituted 2-(aminopyridyl)- and 2-(aminopyrimidinyl)thiazole-5-carboxamides was identified as potent Src/Abl kinase inhibitors with excellent antiproliferative activity against hematological and solid tumor cell lines. Compound 13 was orally active in a K562 xenograft model of chronic myelogenous leukemia (CML), demonstrating complete tumor regressions and low toxicity at multiple dose levels. On the basis of its robust in vivo activity and favorable pharmacokinetic profile, 13 was selected for additional characterization for oncology indications.