2-Aryl-3,3,3-trifluoro-2-hydroxypropionic acids: a new class of protein tyrosine phosphatase 1B inhibitors

David R. Adams; Achamma Abraham; Jun Asano; Catherine Breslin; Colin A.J. Dick; Ulrich Ixkes; Blair F. Johnston; Derek Johnston; Justin Kewnay; Simon P. Mackay; Simon J. MacKenzie; Morag McFarlane; Lee Mitchell; Daniel Spinks; Yasuo Takano

doi:10.1016/j.bmcl.2007.09.069

2-Aryl-3,3,3-trifluoro-2-hydroxypropionic acids: a new class of protein tyrosine phosphatase 1B inhibitors

David R. Adams^*, Achamma Abraham, Jun Asano, Catherine Breslin, Colin A.J. Dick, Ulrich Ixkes, Blair F. Johnston, Derek Johnston, Justin Kewnay, Simon P. Mackay, Simon J. MacKenzie, Morag McFarlane, Lee Mitchell, Daniel Spinks, Yasuo Takano

^*Corresponding author for this work

Strathclyde Institute Of Pharmacy And Biomedical Sciences

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

29 Citations (Scopus)

Abstract

A new series of non-peptidic, mono-acid protein tyrosine phosphatase 1B (PTP1B) inhibitors has been identified by structure-based design. Compounds with 2-(indol-3-yl)- and 2-phenyl-3,3,3-trifluoro-2-hydroxypropionic acid core units targeted at the enzyme's primary site and a hydrophobic chlorophenylthiazole extension in its 2° site exhibit 3-60 μM IC₅₀s for PTP1B inhibition in an Sf9 cell-based assay.

Original language	English
Pages (from-to)	6579-6583
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	23
DOIs	https://doi.org/10.1016/j.bmcl.2007.09.069
Publication status	Published - 1 Dec 2007

Keywords

diabetes
indole
inhibitor
insulin resistance
insulin sensitivity
obesity
phospho-tyrosine
protein tyrosine phosphatase 1B
PTP1B
structure-based design
thiazole

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10.1016/j.bmcl.2007.09.069

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Adams, D. R., Abraham, A., Asano, J., Breslin, C., Dick, C. A. J., Ixkes, U., Johnston, B. F., Johnston, D., Kewnay, J., Mackay, S. P., MacKenzie, S. J., McFarlane, M., Mitchell, L., Spinks, D., & Takano, Y. (2007). 2-Aryl-3,3,3-trifluoro-2-hydroxypropionic acids: a new class of protein tyrosine phosphatase 1B inhibitors. Bioorganic and Medicinal Chemistry Letters , 17(23), 6579-6583. https://doi.org/10.1016/j.bmcl.2007.09.069

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abstract = "A new series of non-peptidic, mono-acid protein tyrosine phosphatase 1B (PTP1B) inhibitors has been identified by structure-based design. Compounds with 2-(indol-3-yl)- and 2-phenyl-3,3,3-trifluoro-2-hydroxypropionic acid core units targeted at the enzyme's primary site and a hydrophobic chlorophenylthiazole extension in its 2° site exhibit 3-60 μM IC50s for PTP1B inhibition in an Sf9 cell-based assay.",

keywords = "diabetes, indole, inhibitor, insulin resistance, insulin sensitivity, obesity, phospho-tyrosine, protein tyrosine phosphatase 1B, PTP1B, structure-based design, thiazole",

author = "Adams, {David R.} and Achamma Abraham and Jun Asano and Catherine Breslin and Dick, {Colin A.J.} and Ulrich Ixkes and Johnston, {Blair F.} and Derek Johnston and Justin Kewnay and Mackay, {Simon P.} and MacKenzie, {Simon J.} and Morag McFarlane and Lee Mitchell and Daniel Spinks and Yasuo Takano",

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Adams, DR, Abraham, A, Asano, J, Breslin, C, Dick, CAJ, Ixkes, U, Johnston, BF, Johnston, D, Kewnay, J, Mackay, SP, MacKenzie, SJ, McFarlane, M, Mitchell, L, Spinks, D & Takano, Y 2007, '2-Aryl-3,3,3-trifluoro-2-hydroxypropionic acids: a new class of protein tyrosine phosphatase 1B inhibitors', Bioorganic and Medicinal Chemistry Letters , vol. 17, no. 23, pp. 6579-6583. https://doi.org/10.1016/j.bmcl.2007.09.069

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T2 - a new class of protein tyrosine phosphatase 1B inhibitors

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AU - Abraham, Achamma

AU - Asano, Jun

AU - Breslin, Catherine

AU - Dick, Colin A.J.

AU - Ixkes, Ulrich

AU - Johnston, Blair F.

AU - Johnston, Derek

AU - Kewnay, Justin

AU - Mackay, Simon P.

AU - MacKenzie, Simon J.

AU - McFarlane, Morag

AU - Mitchell, Lee

AU - Spinks, Daniel

AU - Takano, Yasuo

PY - 2007/12/1

Y1 - 2007/12/1

N2 - A new series of non-peptidic, mono-acid protein tyrosine phosphatase 1B (PTP1B) inhibitors has been identified by structure-based design. Compounds with 2-(indol-3-yl)- and 2-phenyl-3,3,3-trifluoro-2-hydroxypropionic acid core units targeted at the enzyme's primary site and a hydrophobic chlorophenylthiazole extension in its 2° site exhibit 3-60 μM IC50s for PTP1B inhibition in an Sf9 cell-based assay.

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KW - diabetes

KW - indole

KW - inhibitor

KW - insulin resistance

KW - insulin sensitivity

KW - obesity

KW - phospho-tyrosine

KW - protein tyrosine phosphatase 1B

KW - PTP1B

KW - structure-based design

KW - thiazole

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

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ER -

2-Aryl-3,3,3-trifluoro-2-hydroxypropionic acids: a new class of protein tyrosine phosphatase 1B inhibitors

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Keywords

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