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.
Wissner
Allan
A
Chemical and Screening Sciences and Oncology Research, Wyeth Research, 401N. Middletown Road, Pearl River, NY 10965, USA. wissnea@wyeth.com
Hamann
Philip R
PR
Nilakantan
Ramaswamy
R
Greenberger
Lee M
LM
Ye
Fei
F
Rapuano
Timothy A
TA
Loganzo
Frank
F
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