Heterobiaryl purine derivatives as potent antiproliferative agents: inhibitors of cyclin dependent kinases. Part II.
C-6 Biarylmethylamino purine derivatives of roscovitine (1) inhibit cyclin dependent kinases and demonstrate potent antiproliferative activity. Replacement of the aryl rings of the C-6 biarylmethylamino group with heterobiaryl rings has provided compounds with significantly improved activity. In particular, derivatives 18 g and 9 c demonstrated 1000-fold and 1250-fold improvements, respectively, in the growth inhibition of HeLa cells compared to roscovitine (1).
AMRI, Medicinal Chemistry Department, 26 Corporate Circle, Albany, NY 12212-5098, USA.
Michael P
MP
Trova
Keith D
KD
Barnes
Luis
L
Alicea
Travis
T
Benanti
Mark
M
Bielaska
Joseph
J
Bilotta
Brian
B
Bliss
Thuy Nguyen
TN
Duong
Simon
S
Haydar
R Jason
RJ
Herr
Yu
Y
Hui
Matthew
M
Johnson
John M
JM
Lehman
Denise
D
Peace
Matthew
M
Rainka
Patricia
P
Snider
Susan
S
Salamone
Steven
S
Tregay
Xiaozhang
X
Zheng
Thomas D
TD
Friedrich
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D006801:Humans; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011687:Purines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000077546:Roscovitine; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011687:Purines; D000077546:Roscovitine; D018844:Cyclin-Dependent Kinases