title: Syk inhibitors with high potency in presence of blood.
abstract: We describe two series of Syk inhibitors which potently abrogate Syk kinase function in enzymatic assays, cellular assays and in primary cells in the presence of blood. Introduction of a 7-aminoindole substituent led to derivatives with good kinase selectivity and little or no hERG channel inhibition (3b, 10c).
authors.affiliation: Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland. Electronic address: gebhard.thoma@novartis.com.
authors.forename: Gebhard
authors.initials: G
authors.lastname: Thoma
authors.affiliation: Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
authors.forename: Joachim
authors.initials: J
authors.lastname: Blanz
authors.affiliation: Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Bühlmayer
authors.affiliation: Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
authors.forename: Peter
authors.initials: P
authors.lastname: Drückes
authors.affiliation: Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Kittelmann
authors.affiliation: Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Smith
authors.affiliation: Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
authors.forename: Maurice
authors.initials: M
authors.lastname: van Eis
authors.affiliation: Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
authors.forename: Eric
authors.initials: E
authors.lastname: Vangrevelinghe
authors.affiliation: Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
authors.forename: Hans-Günter
authors.initials: HG
authors.lastname: Zerwes
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
authors.forename: Jianwei John
authors.initials: JJ
authors.lastname: Che
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: He
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
authors.forename: Yunho
authors.initials: Y
authors.lastname: Jin
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
authors.forename: Christian C
authors.initials: CC
authors.lastname: Lee
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Michellys
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Uno
authors.affiliation: Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Liu
mesh_terms: D006801:Humans; D007211:Indoles / Q000097:blood / Q000737:chemistry / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000097:blood*; D047428:Protein Kinase Inhibitors / Q000097:blood* / Q000737:chemistry / Q000494:pharmacology*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000097:blood*; D000072377:Syk Kinase
chemical_list: D007211:Indoles; D047908:Intracellular Signaling Peptides and Proteins; D047428:Protein Kinase Inhibitors; D011505:Protein-Tyrosine Kinases; C000606896:SYK protein, human; D000072377:Syk Kinase
keywords: Aldehyde oxidase; BIIB-057; Fostamatinib; Kinase inhibitors; Spleen tyrosine kinase