Facile preparation of new 4-phenylamino-3-quinolinecarbonitrile Src kinase inhibitors via 7-fluoro intermediates: identification of potent 7-amino analogs.
Bioorg Med Chem, 2008/1/01;16(1):405-12.
Boschelli DH[1], Wu B, Ye F, Durutlic H, Golas JM, Lucas J, Boschelli F
Affiliations
PMID: 17905586
Impact factor: 3.461
Abstract
A more efficient preparation of 4-[(2,4-dichloro-5-methoxyphenyl)amino]-7-fluoro-6-methoxy-3-quinolinecarbonitrile (2), the penultimate intermediate in the synthesis of bosutinib (1a), was developed. New 7-alkoxy-4-phenylamino-3-quinolinecarbonitrile Src inhibitors were prepared from 5 and 9, the 6-ethoxy and 6-hydrogen analogs of 2. In addition, the fluoro group of 2 was readily displaced by primary and secondary amines to give 7-amino analogs. Two of these 7-amino analogs, 15 and 18, were potent Src inhibitors with in vivo activity.
MeSH terms
Amines; Animals; Cell Line; Cell Proliferation; Humans; Inhibitory Concentration 50; Nitriles; Protein Kinase Inhibitors; Quinolines; Rats; Structure-Activity Relationship; src-Family Kinases
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