Discovery of a potent and selective aurora kinase inhibitor.
This communication describes the discovery of a novel series of Aurora kinase inhibitors. Key SAR and critical binding elements are discussed. Some of the more advanced analogues potently inhibit cellular proliferation and induce phenotypes consistent with Aurora kinase inhibition. In particular, compound 21 (SNS-314) is a potent and selective Aurora kinase inhibitor that exhibits significant activity in pre-clinical in vivo tumor models.
Oslob
Johan D
JD
Medicinal Chemistry, Sunesis Pharmaceuticals, 395 Oyster Point Boulevard, South San Francisco, CA 94080, USA.
Romanowski
Michael J
MJ
Allen
Darin A
DA
Baskaran
Subramanian
S
Bui
Minna
M
Elling
Robert A
RA
Flanagan
William M
WM
Fung
Amy D
AD
Hanan
Emily J
EJ
Harris
Shannon
S
Heumann
Stacey A
SA
Hoch
Ute
U
Jacobs
Jeffrey W
JW
Lam
Joni
J
Lawrence
Chris E
CE
McDowell
Robert S
RS
Nannini
Michelle A
MA
Shen
Wang
W
Silverman
Jeffrey A
JA
Sopko
Michelle M
MM
Tangonan
Bradley T
BT
Teague
Juli
J
Yoburn
Josh C
JC
Yu
Chul H
CH
Zhong
Min
M
Zimmerman
Kristin M
KM
O'Brien
Tom
T
Lew
Willard
W
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D064127:Aurora Kinases; D004354:Drug Screening Assays, Antitumor; D045325:HCT116 Cells; D006801:Humans; D051379:Mice; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000201:enzymology; D010671:Phenylurea Compounds / Q000737:chemistry* / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology*
D000970:Antineoplastic Agents; D010671:Phenylurea Compounds; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C532454:SNS 314; D013844:Thiazoles; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases