Synthesis and biological study of 2-amino-4-aryl-5-chloropyrimidine analogues as inhibitors of VEGFR-2 and cyclin dependent kinase 1 (CDK1).
The series of 2-amino-4-aryl-5-chloropyrimidines was discovered to be potent for both VEGFR-2 and CDK1. Described here are the chemistry for analogue synthesis, SAR study, and its kinase selectivity prolifing. The full rat PK data and in vivo efficacy study are also included.
Huang
Shenlin
S
Johnson & Johnson Pharmaceutical Research & Development, L.L.C, 1000 Route 202, Raritan, NJ 08869, USA. shenlinhuang@hotmail.com
Li
Ronghua
R
Connolly
Peter J
PJ
Emanuel
Stuart
S
Fuentes-Pesquera
Angel
A
Adams
Mary
M
Gruninger
Robert H
RH
Seraj
Jabed
J
Middleton
Steven A
SA
Davis
Jeremy M
JM
Moffat
David F C
DF
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics; D001682:Biological Availability; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015394:Molecular Structure; D010599:Pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D040301:Vascular Endothelial Growth Factor Receptor-2; D016203:CDC2 Protein Kinase