Versatile templates for the development of novel kinase inhibitors: Discovery of novel CDK inhibitors.
A series of four bicyclic cores were prepared and evaluated as cyclin-dependent kinase-2 (CDK2) inhibitors. From the in-vitro and cell-based analysis, the pyrazolo[1,5-a]pyrimidine core (represented by 9) emerged as the superior core for further elaboration in the identification of novel CDK2 inhibitors.
Dwyer
Michael P
MP
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. michael.dwyer@spcorp.com
Paruch
Kamil
K
Alvarez
Carmen
C
Doll
Ronald J
RJ
Keertikar
Kerry
K
Duca
Jose
J
Fischmann
Thierry O
TO
Hruza
Alan
A
Madison
Vincent
V
Lees
Emma
E
Parry
David
D
Seghezzi
Wolfgang
W
Sgambellone
Nicole
N
Shanahan
Frances
F
Wiswell
Derek
D
Guzi
Timothy J
TJ
D001665:Binding Sites; D018360:Crystallography, X-Ray; D051357:Cyclin-Dependent Kinase 2 / Q000737:chemistry / Q000187:drug effects*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015195:Drug Design; D020128:Inhibitory Concentration 50; D015394:Molecular Structure; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C527752:pyrazolo(1,5-a)pyrimidine; D051357:Cyclin-Dependent Kinase 2