Thienopyrimidine-based dual EGFR/ErbB-2 inhibitors.
Two new series of potent and selective dual EGFR/ErbB-2 kinase inhibitors derived from novel thienopyrimidine cores have been identified. Isomeric thienopyrimidine cores were evaluated as isosteres for a 4-anilinoquinazoline core and several analogs containing the thieno[3,2-d]pyrimidine core showed anti-proliferative activity with IC(50) values less than 1 microM against human tumor cells in vitro.
Rheault
Tara R
TR
Department of Oncology Medicinal Chemistry, GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. tara.r.rheault@gsk.com
Caferro
Thomas R
TR
Dickerson
Scott H
SH
Donaldson
Kelly H
KH
Gaul
Michael D
MD
Goetz
Aaron S
AS
Mullin
Robert J
RJ
McDonald
Octerloney B
OB
Petrov
Kimberly G
KG
Rusnak
David W
DW
Shewchuk
Lisa M
LM
Spehar
Glenn M
GM
Truesdale
Anne T
AT
Vanderwall
Dana E
DE
Wood
Edgar R
ER
Uehling
David E
DE
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066246:ErbB Receptors / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D000077341:Lapatinib; D008956:Models, Chemical; D008968:Molecular Conformation; D011743:Pyrimidines / Q000737:chemistry*; D011799:Quinazolines / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D000077341:Lapatinib; D011743:Pyrimidines; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C476003:thienopyrimidine