title: Identification and SAR of a new series of thieno[3,2-d]pyrimidines as Tpl2 kinase inhibitors.
abstract: We report here the synthesis and SAR of a new series of thieno[3,2-d]pyrimidines as potent Tpl2 kinase inhibitors. The proposed binding mode suggests the potential flipped binding mode depending on the substitution. Biacore studies show evidence of binding of these molecules to the protein kinase. The kinome inhibition profile of these molecules suggests good selectivity.
authors.affiliation: Medicinal Chemistry, Pfizer, 200 Cambridge Park Drive, Cambridge, MA 02140, USA. yike.ni@pfizer.com
authors.forename: Yike
authors.initials: Y
authors.lastname: Ni
authors.forename: Ariamala
authors.initials: A
authors.lastname: Gopalsamy
authors.forename: Derek
authors.initials: D
authors.lastname: Cole
authors.forename: Yonghan
authors.initials: Y
authors.lastname: Hu
authors.forename: Rajiah
authors.initials: R
authors.lastname: Denny
authors.forename: Manus
authors.initials: M
authors.lastname: Ipek
authors.forename: Julie
authors.initials: J
authors.lastname: Liu
authors.forename: Julie
authors.initials: J
authors.lastname: Lee
authors.forename: J Perry
authors.initials: JP
authors.lastname: Hall
authors.forename: Michael
authors.initials: M
authors.lastname: Luong
authors.forename: Jean-Baptiste
authors.initials: JB
authors.lastname: Telliez
authors.forename: Lih-Ling
authors.initials: LL
authors.lastname: Lin
mesh_terms: D000818:Animals; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D006801:Humans; D020128:Inhibitory Concentration 50; D020930:MAP Kinase Kinase Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008862:Microsomes, Liver; D058990:Molecular Targeted Therapy; D009000:Monocytes; D009369:Neoplasms / Q000188:drug therapy; D010766:Phosphorylation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011743:Pyrimidines / Q000737:chemistry; D051381:Rats; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D011743:Pyrimidines; D020930:MAP Kinase Kinase Kinases; C069937:MAP3K8 protein, human