Lead identification to generate 3-cyanoquinoline inhibitors of insulin-like growth factor receptor (IGF-1R) for potential use in cancer treatment.
Insulin-like growth factor receptor (IGF-1R) is a growth factor receptor tyrosine kinase that acts as a critical mediator of cell proliferation and survival. Inhibitors of this receptor are believed to provide a new target in cancer therapy. We previously reported an isoquinolinedione series of IGF-1R inhibitors. Now we have identified a series of 3-cyanoquinoline compounds that are low nanomolar inhibitors of IGF-1R. The strategies, synthesis, and SAR behind the cyanoquinoline scaffold will be discussed.
Miller
Lori M
LM
Wyeth Research, Chemical & Screening Sciences, Princeton, NJ, USA. millerl9@wyeth.com
Mayer
Scott C
SC
Berger
Dan M
DM
Boschelli
Diane H
DH
Boschelli
Frank
F
Di
Li
L
Du
Xuemei
X
Dutia
Minu
M
Floyd
Middleton B
MB
Johnson
Mark
M
Kenny
Cynthia Hess
CH
Krishnamurthy
Girija
G
Moy
Franklin
F
Petusky
Susan
S
Tkach
Diane
D
Torres
Nancy
N
Wu
Biqi
B
Xu
Weixin
W
D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D006801:Humans; D009570:Nitriles / Q000138:chemical synthesis* / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis* / Q000494:pharmacology; D017526:Receptor, IGF Type 1 / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D009570:Nitriles; D011804:Quinolines; D017526:Receptor, IGF Type 1