Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517.

Islam, Imadul; Brown, Greg; Bryant, Judi; Hrvatin, Paul; Kochanny, Monica J; Phillips, Gary B; Yuan, Shendong; Adler, Marc; Whitlow, Marc; Lentz, Dao; Polokoff, Mark A; Wu, James; Shen, Jun; Walters, Janette; Ho, Elena; Subramanyam, Babu; Zhu, Daguang; Feldman, Richard I; Arnaiz, Damian O

Islam, Imadul; Brown, Greg; Bryant, Judi; Hrvatin, Paul; Kochanny, Monica J; Phillips, Gary B; Yuan, Shendong; Adler, Marc; Whitlow, Marc; Lentz, Dao; Polokoff, Mark A; Wu, James; Shen, Jun; Walters, Janette; Ho, Elena; Subramanyam, Babu; Zhu, Daguang; Feldman, Richard I; Arnaiz, Damian O.

Afiliação

Islam I; Berlex Biosciences, 2600 Hilltop Dr. Richmond, CA 94804, USA. imadulislam@yahoo.com

Bioorg Med Chem Lett ; 17(14): 3819-25, 2007 Jul 15.

Article em En | MEDLINE | ID: mdl-17544272

ABSTRACT

ABSTRACT

Based on the lead compound BX-517, a series of C-4' substituted indolinones have been synthesized and evaluated for PDK1 inhibition. Modification at C-4' of the pyrrole afforded potent compounds (7b and 7d) with improved solubility and ADME properties. In this letter, we describe the synthesis, selectivity profile, and pharmacokinetic data of selected compounds.

Assuntos

Indóis/química; Inibidores de Proteínas Quinases/farmacologia; Proteínas Serina-Treonina Quinases/antagonistas & inibidores; Ureia/análogos & derivados; Proteínas Quinases Dependentes de 3-Fosfoinositídeo; Linhagem Celular Tumoral; Humanos; Indóis/farmacologia; Inibidores de Proteínas Quinases/química; Ureia/química; Ureia/farmacologia

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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Ureia / Proteínas Serina-Treonina Quinases / Inibidores de Proteínas Quinases / Indóis Limite: Humans Idioma: En Revista: Bioorg Med Chem Lett Ano de publicação: 2007 Tipo de documento: Article

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