Design and synthesis of 2-amino-isoxazolopyridines as Polo-like kinase inhibitors.
A series of 2-amino-isoxazolopyridines was designed and synthesized as Polo-like kinase (Plk) inhibitors. Key SAR and crystallographic data are discussed. More advanced analogues inhibit Plk1 with good enzymatic activity and modest cell-based activity. Differential selectivity among the three Plk isoforms is observed.
Hanan
Emily J
EJ
Sunesis Pharmaceuticals, Inc., 395 Oyster Point Boulevard Suite 400, South San Francisco, CA 94080, USA. info@sunesis.com
Fucini
Raymond V
RV
Romanowski
Michael J
MJ
Elling
Robert A
RA
Lew
Willard
W
Purkey
Hans E
HE
VanderPorten
Erica C
EC
Yang
Wenjin
W
D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors*; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects; D008968:Molecular Conformation; D015394:Molecular Structure; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors*; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D000097869:Polo-Like Kinase 1
D018797:Cell Cycle Proteins; D007527:Isoenzymes; D007555:Isoxazoles; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D011725:Pyridines; D000097869:Polo-Like Kinase 1