title: Discovery and optimization of thieno[2,3-d]pyrimidines as B-Raf inhibitors.
abstract: The serine/threonine specific protein kinase B-Raf is part of the MAPK pathway and is an interesting oncology target. We have identified thieno[2,3-d]pyrimidines as a core scaffold of small molecule B-Raf inhibitors. The SAR of analogs in this series will be described.
authors.affiliation: Celgene Corporation, San Diego, 4550 Towne Centre Ct, San Diego, CA 92121, United States. gkpackardca@gmail.com
authors.forename: Garrick K
authors.initials: GK
authors.lastname: Packard
authors.forename: Patrick
authors.initials: P
authors.lastname: Papa
authors.forename: Jennifer R
authors.initials: JR
authors.lastname: Riggs
authors.forename: Paul
authors.initials: P
authors.lastname: Erdman
authors.forename: Lida
authors.initials: L
authors.lastname: Tehrani
authors.forename: Dale
authors.initials: D
authors.lastname: Robinson
authors.forename: Roy
authors.initials: R
authors.lastname: Harris
authors.forename: Graziella
authors.initials: G
authors.lastname: Shevlin
authors.forename: Sophie
authors.initials: S
authors.lastname: Perrin-Ninkovic
authors.forename: Robert
authors.initials: R
authors.lastname: Hilgraf
authors.forename: Margaret A
authors.initials: MA
authors.lastname: McCarrick
authors.forename: Tam
authors.initials: T
authors.lastname: Tran
authors.forename: Yuedi
authors.initials: Y
authors.lastname: Fleming
authors.forename: April
authors.initials: A
authors.lastname: Bai
authors.forename: Samantha
authors.initials: S
authors.lastname: Richardson
authors.forename: Jason
authors.initials: J
authors.lastname: Katz
authors.forename: Yang
authors.initials: Y
authors.lastname: Tang
authors.forename: Jim
authors.initials: J
authors.lastname: Leisten
authors.forename: Mehran
authors.initials: M
authors.lastname: Moghaddam
authors.forename: Brian
authors.initials: B
authors.lastname: Cathers
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.forename: Steven
authors.initials: S
authors.lastname: Sakata
mesh_terms: D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D020935:MAP Kinase Signaling System; D008956:Models, Chemical; D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D048493:Proto-Oncogene Proteins B-raf / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D011743:Pyrimidines / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014508:Urea / Q000737:chemistry
chemical_list: D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors; D011743:Pyrimidines; D014508:Urea; D048493:Proto-Oncogene Proteins B-raf; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4