2D-QSAR and 3D-QSAR/CoMSIA studies on a series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-phenylethan-1-ol with human β3-adrenergic activity

Gastón Apablaza, Luisa Montoya, Cesar Morales-Verdejo, Marco Mellado, Mauricio Cuellar, Carlos F. Lagos, Jorge Soto-Delgado, Hery Chung, Carlos David Pessoa-Mahana, Jaime Mella

Resultado de la investigación: Contribución a la publicaciónArticle

Resumen

The β3 adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA (Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new β3 adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis) study on a series of potent β3 adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving β3 adrenergic activity is given.

Idioma originalEnglish
Número de artículo404
PublicaciónMolecules
Volumen22
Número de edición3
Identificadores de objetos digitales
EstadoPublished - 1 mar 2017

Huella dactilar

Quantitative Structure-Activity Relationship
Adrenergic Agents
Ligands
Overactive Urinary Bladder
Adrenergic Agonists
United States Food and Drug Administration
Adrenergic Receptors
Hydrogen
Heart Diseases
Obesity
Pathology
Delivery of Health Care

Keywords

    ASJC Scopus subject areas

    • Medicine(all)
    • Organic Chemistry

    Citar esto

    Apablaza, G., Montoya, L., Morales-Verdejo, C., Mellado, M., Cuellar, M., Lagos, C. F., ... Mella, J. (2017). 2D-QSAR and 3D-QSAR/CoMSIA studies on a series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-phenylethan-1-ol with human β3-adrenergic activity. Molecules, 22(3), [404]. DOI: 10.3390/molecules22030404

    Apablaza, Gastón; Montoya, Luisa; Morales-Verdejo, Cesar; Mellado, Marco; Cuellar, Mauricio; Lagos, Carlos F.; Soto-Delgado, Jorge; Chung, Hery; Pessoa-Mahana, Carlos David; Mella, Jaime / 2D-QSAR and 3D-QSAR/CoMSIA studies on a series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-phenylethan-1-ol with human β3-adrenergic activity.

    En: Molecules, Vol. 22, N.º 3, 404, 01.03.2017.

    Resultado de la investigación: Contribución a la publicaciónArticle

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    title = "2D-QSAR and 3D-QSAR/CoMSIA studies on a series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-phenylethan-1-ol with human β3-adrenergic activity",
    abstract = "The β3 adrenergic receptor is raising as an important drug target for the treatment of pathologies such as diabetes, obesity, depression, and cardiac diseases among others. Several attempts to obtain selective and high affinity ligands have been made. Currently, Mirabegron is the only available drug on the market that targets this receptor approved for the treatment of overactive bladder. However, the FDA (Food and Drug Administration) in USA and the MHRA (Medicines and Healthcare products Regulatory Agency) in UK have made reports of potentially life-threatening side effects associated with the administration of Mirabegron, casting doubts on the continuity of this compound. Therefore, it is of utmost importance to gather information for the rational design and synthesis of new β3 adrenergic ligands. Herein, we present the first combined 2D-QSAR (two-dimensional Quantitative Structure-Activity Relationship) and 3D-QSAR/CoMSIA (three-dimensional Quantitative Structure-Activity Relationship/Comparative Molecular Similarity Index Analysis) study on a series of potent β3 adrenergic agonists of indole-alkylamine structure. We found a series of changes that can be made in the steric, hydrogen-bond donor and acceptor, lipophilicity and molar refractivity properties of the compounds to generate new promising molecules. Finally, based on our analysis, a summary and a regiospecific description of the requirements for improving β3 adrenergic activity is given.",
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    author = "Gastón Apablaza and Luisa Montoya and Cesar Morales-Verdejo and Marco Mellado and Mauricio Cuellar and Lagos, {Carlos F.} and Jorge Soto-Delgado and Hery Chung and Pessoa-Mahana, {Carlos David} and Jaime Mella",
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    Apablaza, G, Montoya, L, Morales-Verdejo, C, Mellado, M, Cuellar, M, Lagos, CF, Soto-Delgado, J, Chung, H, Pessoa-Mahana, CD & Mella, J 2017, '2D-QSAR and 3D-QSAR/CoMSIA studies on a series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-phenylethan-1-ol with human β3-adrenergic activity' Molecules, vol. 22, n.º 3, 404. DOI: 10.3390/molecules22030404

    2D-QSAR and 3D-QSAR/CoMSIA studies on a series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-phenylethan-1-ol with human β3-adrenergic activity. / Apablaza, Gastón; Montoya, Luisa; Morales-Verdejo, Cesar; Mellado, Marco; Cuellar, Mauricio; Lagos, Carlos F.; Soto-Delgado, Jorge; Chung, Hery; Pessoa-Mahana, Carlos David; Mella, Jaime.

    En: Molecules, Vol. 22, N.º 3, 404, 01.03.2017.

    Resultado de la investigación: Contribución a la publicaciónArticle

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    AU - Montoya,Luisa

    AU - Morales-Verdejo,Cesar

    AU - Mellado,Marco

    AU - Cuellar,Mauricio

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    AU - Soto-Delgado,Jorge

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    Apablaza G, Montoya L, Morales-Verdejo C, Mellado M, Cuellar M, Lagos CF y otros. 2D-QSAR and 3D-QSAR/CoMSIA studies on a series of (R)-2-((2-(1H-Indol-2-yl)ethyl)amino)-1-phenylethan-1-ol with human β3-adrenergic activity. Molecules. 2017 mar 1;22(3). 404. Disponible desde, DOI: 10.3390/molecules22030404