Syk inhibitors with high potency in presence of blood.

Thoma, Gebhard; Blanz, Joachim; Bühlmayer, Peter; Drückes, Peter; Kittelmann, Matthias; Smith, Alexander B; van Eis, Maurice; Vangrevelinghe, Eric; Zerwes, Hans-Günter; Che, Jianwei John; He, Xiaohui; Jin, Yunho; Lee, Christian C; Michellys, Pierre-Yves; Uno, Tetsuo; Liu, Hong

Thoma, Gebhard; Blanz, Joachim; Bühlmayer, Peter; Drückes, Peter; Kittelmann, Matthias; Smith, Alexander B; van Eis, Maurice; Vangrevelinghe, Eric; Zerwes, Hans-Günter; Che, Jianwei John; He, Xiaohui; Jin, Yunho; Lee, Christian C; Michellys, Pierre-Yves; Uno, Tetsuo; Liu, Hong.

Afiliação

Thoma G; Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland. Electronic address: gebhard.thoma@novartis.com.
Blanz J; Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
Bühlmayer P; Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
Drückes P; Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
Kittelmann M; Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
Smith AB; Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
van Eis M; Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
Vangrevelinghe E; Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
Zerwes HG; Novartis Institutes for Biomedical Research, Forum 1 Novartis Campus, 4056 Basel, Switzerland.
Che JJ; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
He X; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Jin Y; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Lee CC; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Michellys PY; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Uno T; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.
Liu H; Genomics Institute of the Novartis Research Foundation, 10675 John Jay Hopkins Drive, San Diego, CA 92121, USA.

Bioorg Med Chem Lett ; 24(10): 2278-82, 2014 May 15.

Article em En | MEDLINE | ID: mdl-24726806

ABSTRACT

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).

Assuntos

Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores; Peptídeos e Proteínas de Sinalização Intracelular/sangue; Inibidores de Proteínas Quinases/sangue; Inibidores de Proteínas Quinases/farmacologia; Proteínas Tirosina Quinases/antagonistas & inibidores; Proteínas Tirosina Quinases/sangue; Humanos; Indóis/sangue; Indóis/química; Indóis/farmacologia; Inibidores de Proteínas Quinases/química; Quinase Syk

Palavras-chave

Aldehyde oxidase; BIIB-057; Fostamatinib; Kinase inhibitors; Spleen tyrosine kinase

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Proteínas Tirosina Quinases / Peptídeos e Proteínas de Sinalização Intracelular / Inibidores de Proteínas Quinases Limite: Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2014 Tipo de documento: Article

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