Design, synthesis and biological evaluation of novel 3H-imidazole [4,5-b] pyridine derivatives as selective mTOR inhibitors.

Zhang, Lingzhi; Bu, Tantan; Bao, Xiaobo; Liang, Tingting; Ge, Yiran; Xu, Yungen; Zhu, Qihua

Zhang, Lingzhi; Bu, Tantan; Bao, Xiaobo; Liang, Tingting; Ge, Yiran; Xu, Yungen; Zhu, Qihua.

Afiliação

Zhang L; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Bu T; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China.
Bao X; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.
Liang T; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.
Ge Y; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China.
Xu Y; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China. Electronic address: xu_yungen@hotmail.com.
Zhu Q; Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 21009, China; Department of Medicinal Chemistry, China Pharmaceutical University, Nanjing 21009, China. Electronic address: zhuqihua@vip.126.com.

Bioorg Med Chem Lett ; 27(15): 3395-3398, 2017 08 01.

Article em En | MEDLINE | ID: mdl-28633896

ABSTRACT

ABSTRACT

A series of 3H-imidazo [4,5-b] pyridines derivatives were designed and synthesized as selective mTOR inhibitors. The systematic optimization of the molecules resulted in the identification of two compounds 10d and 10n with nanomolar mTOR inhibitory activity and selectivity over PI3Kα. Besides, compounds 10d and 10n demonstrated attractive potency against human breast cancer cells (MCF-7) and human ovarian cancer cell (A2780).

Assuntos

Desenho de Fármacos; Imidazóis/farmacologia; Inibidores de Proteínas Quinases/farmacologia; Piridinas/farmacologia; Serina-Treonina Quinases TOR/antagonistas & inibidores; Linhagem Celular Tumoral; Proliferação de Células/efeitos dos fármacos; Relação Dose-Resposta a Droga; Humanos; Imidazóis/síntese química; Imidazóis/química; Estrutura Molecular; Inibidores de Proteínas Quinases/síntese química; Inibidores de Proteínas Quinases/química; Piridinas/síntese química; Piridinas/química; Relação Estrutura-Atividade

Palavras-chave

3H-Imidazo [4,5-b] pyridine; Antitumor; Mammalian target of rapamycin; Synthesis; mTOR inhibitors

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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piridinas / Desenho de Fármacos / Inibidores de Proteínas Quinases / Serina-Treonina Quinases TOR / Imidazóis Idioma: En Ano de publicação: 2017 Tipo de documento: Article

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