Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability

Research output: Contribution to journal › Journal article › Research › peer-review

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Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability. / Christiansen, Elisabeth; Due-Hansen, Maria E; Urban, Christian; Grundmann, Manuel; Schmidt, Johannes; Hansen, Steffen V F; Hudson, Brian D; Zaibi, Mohamed; Markussen, Stine B; Hagesaether, Ellen; Milligan, Graeme; Cawthorne, Michael A; Kostenis, Evi; Kassack, Matthias U; Ulven, Trond.

In: Journal of Medicinal Chemistry, Vol. 56, No. 3, 14.02.2013, p. 982-992.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Christiansen, E, Due-Hansen, ME, Urban, C, Grundmann, M, Schmidt, J, Hansen, SVF, Hudson, BD, Zaibi, M, Markussen, SB, Hagesaether, E, Milligan, G, Cawthorne, MA, Kostenis, E, Kassack, MU & Ulven, T 2013, 'Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability', Journal of Medicinal Chemistry, vol. 56, no. 3, pp. 982-992. https://doi.org/10.1021/jm301470a

APA

Christiansen, E., Due-Hansen, M. E., Urban, C., Grundmann, M., Schmidt, J., Hansen, S. V. F., Hudson, B. D., Zaibi, M., Markussen, S. B., Hagesaether, E., Milligan, G., Cawthorne, M. A., Kostenis, E., Kassack, M. U., & Ulven, T. (2013). Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability. Journal of Medicinal Chemistry, 56(3), 982-992. https://doi.org/10.1021/jm301470a

Vancouver

Christiansen E, Due-Hansen ME, Urban C, Grundmann M, Schmidt J, Hansen SVF et al. Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability. Journal of Medicinal Chemistry. 2013 Feb 14;56(3):982-992. https://doi.org/10.1021/jm301470a

Author

Christiansen, Elisabeth ; Due-Hansen, Maria E ; Urban, Christian ; Grundmann, Manuel ; Schmidt, Johannes ; Hansen, Steffen V F ; Hudson, Brian D ; Zaibi, Mohamed ; Markussen, Stine B ; Hagesaether, Ellen ; Milligan, Graeme ; Cawthorne, Michael A ; Kostenis, Evi ; Kassack, Matthias U ; Ulven, Trond. / Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability. In: Journal of Medicinal Chemistry. 2013 ; Vol. 56, No. 3. pp. 982-992.

Bibtex

@article{560175e1124647118b6285c95ce1c60d,
title = "Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability",
abstract = "The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes. Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity. We have previously reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral bioavailability, and appreciable efficacy on glucose tolerance in mice.",
keywords = "Administration, Oral, Animals, Biological Availability, Drug Discovery, Magnetic Resonance Spectroscopy, Mice, Models, Molecular, Receptors, G-Protein-Coupled, Spectrometry, Mass, Electrospray Ionization, Structure-Activity Relationship",
author = "Elisabeth Christiansen and Due-Hansen, {Maria E} and Christian Urban and Manuel Grundmann and Johannes Schmidt and Hansen, {Steffen V F} and Hudson, {Brian D} and Mohamed Zaibi and Markussen, {Stine B} and Ellen Hagesaether and Graeme Milligan and Cawthorne, {Michael A} and Evi Kostenis and Kassack, {Matthias U} and Trond Ulven",
year = "2013",
month = feb,
day = "14",
doi = "10.1021/jm301470a",
language = "English",
volume = "56",
pages = "982--992",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "3",

}

RIS

TY - JOUR

T1 - Discovery of a potent and selective free fatty acid receptor 1 agonist with low lipophilicity and high oral bioavailability

AU - Christiansen, Elisabeth

AU - Due-Hansen, Maria E

AU - Urban, Christian

AU - Grundmann, Manuel

AU - Schmidt, Johannes

AU - Hansen, Steffen V F

AU - Hudson, Brian D

AU - Zaibi, Mohamed

AU - Markussen, Stine B

AU - Hagesaether, Ellen

AU - Milligan, Graeme

AU - Cawthorne, Michael A

AU - Kostenis, Evi

AU - Kassack, Matthias U

AU - Ulven, Trond

PY - 2013/2/14

Y1 - 2013/2/14

N2 - The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes. Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity. We have previously reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral bioavailability, and appreciable efficacy on glucose tolerance in mice.

AB - The free fatty acid receptor 1 (FFA1, also known as GPR40) mediates enhancement of glucose-stimulated insulin secretion and is emerging as a new target for the treatment of type 2 diabetes. Several FFA1 agonists are known, but the majority of these suffer from high lipophilicity. We have previously reported the FFA1 agonist 3 (TUG-424). We here describe the continued structure-activity exploration and optimization of this compound series, leading to the discovery of the more potent agonist 40, a compound with low lipophilicity, excellent in vitro metabolic stability and permeability, complete oral bioavailability, and appreciable efficacy on glucose tolerance in mice.

KW - Administration, Oral

KW - Animals

KW - Biological Availability

KW - Drug Discovery

KW - Magnetic Resonance Spectroscopy

KW - Mice

KW - Models, Molecular

KW - Receptors, G-Protein-Coupled

KW - Spectrometry, Mass, Electrospray Ionization

KW - Structure-Activity Relationship

U2 - 10.1021/jm301470a

DO - 10.1021/jm301470a

M3 - Journal article

VL - 56

SP - 982

EP - 992

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 3

ER -

ID: 189162297