title: Synthesis and biological study of 2-amino-4-aryl-5-chloropyrimidine analogues as inhibitors of VEGFR-2 and cyclin dependent kinase 1 (CDK1).
abstract: 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.
authors.affiliation: Johnson & Johnson Pharmaceutical Research & Development, L.L.C, 1000 Route 202, Raritan, NJ 08869, USA. shenlinhuang@hotmail.com
authors.forename: Shenlin
authors.initials: S
authors.lastname: Huang
authors.forename: Ronghua
authors.initials: R
authors.lastname: Li
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Connolly
authors.forename: Stuart
authors.initials: S
authors.lastname: Emanuel
authors.forename: Angel
authors.initials: A
authors.lastname: Fuentes-Pesquera
authors.forename: Mary
authors.initials: M
authors.lastname: Adams
authors.forename: Robert H
authors.initials: RH
authors.lastname: Gruninger
authors.forename: Jabed
authors.initials: J
authors.lastname: Seraj
authors.forename: Steven A
authors.initials: SA
authors.lastname: Middleton
authors.forename: Jeremy M
authors.initials: JM
authors.lastname: Davis
authors.forename: David F C
authors.initials: DF
authors.lastname: Moffat
mesh_terms: 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*
chemical_list: D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D040301:Vascular Endothelial Growth Factor Receptor-2; D016203:CDC2 Protein Kinase