Discovery of a cyclopentylamine as an orally active dual NK1 receptor antagonist-serotonin reuptake transporter inhibitor.

Wu, Yong-Jin; He, Huan; Gao, Qi; Wu, Dedong; Bertekap, Robert; Westphal, Ryan S; Lelas, Snjezana; Newton, Amy; Wallace, Tanya; Taber, Matthew; Davis, Carl; Macor, John E; Bronson, Joanne

Wu, Yong-Jin; He, Huan; Gao, Qi; Wu, Dedong; Bertekap, Robert; Westphal, Ryan S; Lelas, Snjezana; Newton, Amy; Wallace, Tanya; Taber, Matthew; Davis, Carl; Macor, John E; Bronson, Joanne.

Afiliação

Wu YJ; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA. Electronic address: yong-jin.wu@bms.com.
He H; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
Gao Q; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
Wu D; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
Bertekap R; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
Westphal RS; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
Lelas S; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
Newton A; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
Wallace T; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
Taber M; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
Davis C; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
Macor JE; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.
Bronson J; Research and Development, Bristol-Myers Squibb Company, 5 Research Parkway, Wallingford, CT 06492, USA.

Bioorg Med Chem Lett ; 24(6): 1611-4, 2014 Mar 15.

Article em En | MEDLINE | ID: mdl-24507922

RESUMO

Cyclopentylamine 4 was identified as a potent dual NK1R antagonist-SERT inhibitor. This compound demonstrated significant oral activity in the gerbil forced swimming test, suggesting that dual NK1R antagonists-SERT inhibitors may be useful in treating depression disorders.

Assuntos

Ciclopentanos/química; Antagonistas dos Receptores de Neurocinina-1/química; Receptores da Neurocinina-1/química; Inibidores Seletivos de Recaptação de Serotonina/química; Proteínas da Membrana Plasmática de Transporte de Serotonina/química; Administração Oral; Animais; Cristalografia por Raios X; Ciclopentanos/síntese química; Ciclopentanos/farmacologia; Avaliação Pré-Clínica de Medicamentos; Gerbillinae; Humanos; Conformação Molecular; Atividade Motora/efeitos dos fármacos; Antagonistas dos Receptores de Neurocinina-1/metabolismo; Antagonistas dos Receptores de Neurocinina-1/farmacologia; Ligação Proteica; Receptores da Neurocinina-1/metabolismo; Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo; Inibidores Seletivos de Recaptação de Serotonina/síntese química; Inibidores Seletivos de Recaptação de Serotonina/farmacologia

Palavras-chave

Dual NK(1) receptor antagonistsserotonin reuptake transporter inhibitor; NK(1) receptor (NK(1)R) antagonist; Serotonin reuptake transporter (SERT) inhibitor

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Inibidores Seletivos de Recaptação de Serotonina / Receptores da Neurocinina-1 / Ciclopentanos / Proteínas da Membrana Plasmática de Transporte de Serotonina / Antagonistas dos Receptores de Neurocinina-1 Limite: Animals / 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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