Syntheses and EGFR kinase inhibitory activity of 6-substituted-4-anilino [1,7] and [1,8] naphthyridine-3-carbonitriles.
The syntheses and EGFR kinase inhibitory activity of a series of 6-substituted-4-anilino [1,7] and [1,8] naphthyridine-3-carbonitriles are described. Both reversible and irreversible binding inhibitors were prepared. These series were compared with each other and with the corresponding 4-anilinoquinoline-3-carbonitriles. Compounds having a 1,7-naphthyridine core structure can retain high potency while those with a 1,8-naphthyridine core are significantly less active. These results are consistent with molecular modeling observations.
Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401N. Middletown Road, Pearl River, NY 10965, USA. wissnea@wyeth.com
Allan
A
Wissner
Philip R
PR
Hamann
Ramaswamy
R
Nilakantan
Lee M
LM
Greenberger
Fei
F
Ye
Timothy A
TA
Rapuano
Frank
F
Loganzo
D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000378:metabolism; D009570:Nitriles / Q000138:chemical synthesis* / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology
D004791:Enzyme Inhibitors; D009287:Naphthyridines; D009570:Nitriles; D066246:ErbB Receptors