Phenylpiperidine-benzoxazinones as urotensin-II receptor antagonists: synthesis, SAR, and in vivo assessment.

Luci, Diane K; Ghosh, Shyamali; Smith, Charles E; Qi, Jenson; Wang, Yuanping; Haertlein, Barbara; Parry, Tom J; Li, Jian; Almond, Harold R; Minor, Lisa K; Damiano, Bruce P; Kinney, William A; Maryanoff, Bruce E; Lawson, Edward C

Luci, Diane K; Ghosh, Shyamali; Smith, Charles E; Qi, Jenson; Wang, Yuanping; Haertlein, Barbara; Parry, Tom J; Li, Jian; Almond, Harold R; Minor, Lisa K; Damiano, Bruce P; Kinney, William A; Maryanoff, Bruce E; Lawson, Edward C.

Afiliação

Luci DK; Research & Early Development, Johnson & Johnson Pharmaceutical Research & Development, Welsh and McKean Roads, Spring House, PA 19477-0776, USA.

Bioorg Med Chem Lett ; 17(23): 6489-92, 2007 Dec 01.

Article em En | MEDLINE | ID: mdl-17933531

RESUMO

Various 4-phenylpiperidine-benzoxazin-3-ones were synthesized and biologically evaluated as urotensin-II (U-II) receptor antagonists. Compound 12i was identified from in vitro evaluation as a low nanomolar antagonist against both rat and human U-II receptors. This compound showed in vivo efficacy in reversing the ear-flush response induced by U-II in rats.

Assuntos

Benzoxazinas/síntese química; Piperidinas/síntese química; Receptores Acoplados a Proteínas G/antagonistas & inibidores; Urotensinas/metabolismo; Animais; Benzoxazinas/farmacologia; Células CHO; Cricetinae; Cricetulus; Humanos; Piperidinas/farmacologia; Ratos; Receptores Acoplados a Proteínas G/fisiologia; Relação Estrutura-Atividade; Urotensinas/antagonistas & inibidores; Urotensinas/fisiologia

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Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Piperidinas / Urotensinas / Receptores Acoplados a Proteínas G / Benzoxazinas Limite: Animals / Humans Idioma: En Revista: Bioorg Med Chem Lett Assunto da revista: BIOQUIMICA / QUIMICA Ano de publicação: 2007 Tipo de documento: Article País de afiliação: Estados Unidos

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