Thiophene inhibitors of PDE4: crystal structures show a second binding mode at the catalytic domain of PDE4D2

Jacob Nankervis; Susanne Feil; Nancy Hancock; Zhaohua Zheng; Hooi-ling Ng; Craig Morton; Jessica Holien; Patricia Ho; Mark Frazzetto; Ian Jennings; David Manallack; T John Martin; Philip Thompson; Michael Parker

doi:10.1016/j.bmcl.2011.09.109

Thiophene inhibitors of PDE4: crystal structures show a second binding mode at the catalytic domain of PDE4D2

Jacob Nankervis, Susanne Feil, Nancy Hancock, Zhaohua Zheng, Hooi-ling Ng, Craig Morton, Jessica Holien, Patricia Ho, Mark Frazzetto, Ian Jennings, David Manallack, T John Martin, Philip Thompson, Michael Parker

Medicinal Chemistry

Research output: Contribution to journal › Article › Research › peer-review

17 Citations (Scopus)

Abstract

PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor. (C) 2011 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	7089 - 7093
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	21
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2011.09.109
Publication status	Published - 2011

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Nankervis, J., Feil, S., Hancock, N., Zheng, Z., Ng, H., Morton, C., Holien, J., Ho, P., Frazzetto, M., Jennings, I., Manallack, D., Martin, T. J., Thompson, P., & Parker, M. (2011). Thiophene inhibitors of PDE4: crystal structures show a second binding mode at the catalytic domain of PDE4D2. Bioorganic and Medicinal Chemistry Letters, 21(23), 7089 - 7093. https://doi.org/10.1016/j.bmcl.2011.09.109

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abstract = "PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor. (C) 2011 Elsevier Ltd. All rights reserved.",

author = "Jacob Nankervis and Susanne Feil and Nancy Hancock and Zhaohua Zheng and Hooi-ling Ng and Craig Morton and Jessica Holien and Patricia Ho and Mark Frazzetto and Ian Jennings and David Manallack and Martin, {T John} and Philip Thompson and Michael Parker",

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language = "English",

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Nankervis, J, Feil, S, Hancock, N, Zheng, Z, Ng, H, Morton, C, Holien, J, Ho, P, Frazzetto, M, Jennings, I, Manallack, D, Martin, TJ, Thompson, P & Parker, M 2011, 'Thiophene inhibitors of PDE4: crystal structures show a second binding mode at the catalytic domain of PDE4D2', Bioorganic and Medicinal Chemistry Letters, vol. 21, no. 23, pp. 7089 - 7093. https://doi.org/10.1016/j.bmcl.2011.09.109

TY - JOUR

T1 - Thiophene inhibitors of PDE4: crystal structures show a second binding mode at the catalytic domain of PDE4D2

AU - Nankervis, Jacob

AU - Feil, Susanne

AU - Hancock, Nancy

AU - Zheng, Zhaohua

AU - Ng, Hooi-ling

AU - Morton, Craig

AU - Holien, Jessica

AU - Ho, Patricia

AU - Frazzetto, Mark

AU - Jennings, Ian

AU - Manallack, David

AU - Martin, T John

AU - Thompson, Philip

AU - Parker, Michael

PY - 2011

Y1 - 2011

N2 - PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor. (C) 2011 Elsevier Ltd. All rights reserved.

AB - PDE4 inhibitors have been identified as therapeutic targets for a variety of conditions, particularly inflammatory diseases. We have serendipitously identified a novel class of phosphodiesterase 4 (PDE4) inhibitor during a study to discover antagonists of the parathyroid hormone receptor. X-ray crystallographic studies of PDE4D2 complexed to four potent inhibitors reveal the atomic details of how they inhibit the enzyme and a notable contrast to another recently reported thiophene-based inhibitor. (C) 2011 Elsevier Ltd. All rights reserved.

UR - http://www.sciencedirect.com.ezproxy.lib.monash.edu.au/science/article/pii/S0960894X11013539

U2 - 10.1016/j.bmcl.2011.09.109

DO - 10.1016/j.bmcl.2011.09.109

M3 - Article

SN - 0960-894X

VL - 21

SP - 7089

EP - 7093

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 23

ER -

Thiophene inhibitors of PDE4: crystal structures show a second binding mode at the catalytic domain of PDE4D2

Abstract

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