The design and synthesis of purine inhibitors of CDK2. III.
Cyclin-dependent kinases (CDKs) belong to a class of enzymes that control the ability of a cell to enter into and proceed through the cell division cycle. Using purine as a scaffold, we have synthesized a number of nanomolar inhibitors of CDK-2/cyclin E. In this report, the synthesis of a series of piperidine-substituted purine analogs will be presented, as well as some of their in vitro and in vivo biological effects.
Shum
P W
PW
Aventis Pharmaceuticals Inc., Rt. 202-206, Bridgewater, New Jersey 08807, USA.
Peet
N P
NP
Weintraub
P M
PM
Le
T B
TB
Zhao
Z
Z
Barbone
F
F
Cashman
B
B
Tsay
J
J
Dwyer
S
S
Loos
P C
PC
Powers
E A
EA
Kropp
K
K
Wright
P S
PS
Bitonti
A
A
Dumont
J
J
Borcherding
D R
DR
D000225:Adenine / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D042846:CDC2-CDC28 Kinases; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D019073:HT29 Cells / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D011687:Purines / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; C442879:MDL 108522; D010880:Piperidines; D011687:Purines; D017346:Protein Serine-Threonine Kinases; D042846:CDC2-CDC28 Kinases; C495894:CDK2 protein, human; C495893:Cdk2 protein, mouse; D051357:Cyclin-Dependent Kinase 2; D018844:Cyclin-Dependent Kinases; D000225:Adenine