Pyrazolone-based anaplastic lymphoma kinase (ALK) inhibitors: control of selectivity by a benzyloxy group

R Tripathy, RJ McHugh, AK Ghose, GR Ott…

Index: Tripathy, Rabindranath; McHugh, Robert J.; Ghose, Arup K.; Ott, Gregory R.; Angeles, Thelma S.; Albom, Mark S.; Huang, Zeck; Aimone, Lisa D.; Cheng, Mangeng; Dorsey, Bruce D. Bioorganic and Medicinal Chemistry Letters, 2011 , vol. 21, # 24 p. 7261 - 7264

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Citation Number: 15

Abstract

Anaplastic lymphoma kinase (ALK) is transmembrane receptor tyrosine kinase, with oncogenic variants that have been implicated in ALCL, NSCLC and other cancers. Screening of a VEGFR2-biased kinase library resulted in identification of 1 which showed cross-reactivity with ALK. SAR on the indole segment of 1 showed that a subtle structural modification (the ethoxy group of 1 changed to a benzyloxy to generate 5a) enhanced ...