Pyrazolo[1,5-a]pyrimidines as orally available inhibitors of cyclin-dependent kinase 2.
Properly substituted pyrazolo[1,5-a]pyrimidines are potent and selective CDK2 inhibitors. Compound 15j is orally available and showed efficacy in a mouse A2780 xenograft model.
Paruch
Kamil
K
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. kamil.paruch@spcorp.com
Dwyer
Michael P
MP
Alvarez
Carmen
C
Brown
Courtney
C
Chan
Tin-Yau
TY
Doll
Ronald J
RJ
Keertikar
Kerry
K
Knutson
Chad
C
McKittrick
Brian
B
Rivera
Jocelyn
J
Rossman
Randall
R
Tucker
Greg
G
Fischmann
Thierry O
TO
Hruza
Alan
A
Madison
Vincent
V
Nomeir
Amin A
AA
Wang
Yaolin
Y
Lees
Emma
E
Parry
David
D
Sgambellone
Nicole
N
Seghezzi
Wolfgang
W
Schultz
Lesley
L
Shanahan
Fran
F
Wiswell
Derek
D
Xu
Xiaoying
X
Zhou
Quiao
Q
James
Ray A
RA
Paradkar
Vidyadhar M
VM
Park
Haengsoon
H
Rokosz
Laura R
LR
Stauffer
Tara M
TM
Guzi
Timothy J
TJ
D000284:Administration, Oral; D000818:Animals; D018360:Crystallography, X-Ray; D051357:Cyclin-Dependent Kinase 2 / Q000037:antagonists & inhibitors* / Q000187:drug effects; D004285:Dogs; D004354:Drug Screening Assays, Antitumor; D000882:Haplorhini; D051379:Mice; D023421:Models, Animal; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D051381:Rats; D023041:Xenograft Model Antitumor Assays
D011720:Pyrazoles; D011725:Pyridines; C447480:pyrazolo(3,4-b)pyridine; D051357:Cyclin-Dependent Kinase 2