2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: A novel class of small molecule heparanase inhibitors

Eddie Mckenzie; Stephen M. Courtney; Philip A. Hay; Richard T. Buck; Claire S. Colville; David W. Porter; David I C Scopes; Faye C. Pollard; Martin J. Page; James M. Bennett; Margaret L. Hircock; Edward A. McKenzie; Colin R. Stubberfield; Paul R. Turner

doi:10.1016/j.bmcl.2004.03.086

2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: A novel class of small molecule heparanase inhibitors

Eddie Mckenzie
, Stephen M. Courtney
, Philip A. Hay
, Richard T. Buck
, Claire S. Colville
, David W. Porter
, David I C Scopes
, Faye C. Pollard
, Martin J. Page
, James M. Bennett
, Margaret L. Hircock
, Edward A. McKenzie
, Colin R. Stubberfield
, Paul R. Turner

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

Abstract

A novel class of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acids are described as inhibitors of the endo-β-glucuronidase heparanase. Several of the compounds, for example, 2-[4-propylamino-5-[5-(4-chloro)phenyl-benzoxazol-2- yl]phenyl]-2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid (9c), display potent heparanase inhibitory activity (IC50 200-500nM) and have high selectivity (>100-fold) over human β-glucuronidase. They also show anti-angiogenic effects. Such compounds should serve as useful biological tools and may provide a basis for the design of novel therapeutic agents. © 2004 Elsevier Ltd. All rights reserved.

Original language	English
Pages (from-to)	3269-3273
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	12
DOIs	https://doi.org/10.1016/j.bmcl.2004.03.086
Publication status	Published - 21 Jun 2004

Keywords

β-Glucuronidase
Angiogenesis
Heparanase
Isoindole-5-carboxylic acid
Metastasis

Research Beacons, Institutes and Platforms

Manchester Institute of Biotechnology

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10.1016/j.bmcl.2004.03.086

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Mckenzie, E., Courtney, S. M., Hay, P. A., Buck, R. T., Colville, C. S., Porter, D. W., Scopes, D. I. C., Pollard, F. C., Page, M. J., Bennett, J. M., Hircock, M. L., McKenzie, E. A., Stubberfield, C. R., & Turner, P. R. (2004). 2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: A novel class of small molecule heparanase inhibitors. Bioorganic and Medicinal Chemistry Letters, 14(12), 3269-3273. https://doi.org/10.1016/j.bmcl.2004.03.086

@article{b22f1db61458409bb0560f4c91a38a2b,

title = "2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: A novel class of small molecule heparanase inhibitors",

abstract = "A novel class of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acids are described as inhibitors of the endo-β-glucuronidase heparanase. Several of the compounds, for example, 2-[4-propylamino-5-[5-(4-chloro)phenyl-benzoxazol-2- yl]phenyl]-2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid (9c), display potent heparanase inhibitory activity (IC50 200-500nM) and have high selectivity (>100-fold) over human β-glucuronidase. They also show anti-angiogenic effects. Such compounds should serve as useful biological tools and may provide a basis for the design of novel therapeutic agents. {\textcopyright} 2004 Elsevier Ltd. All rights reserved.",

keywords = "β-Glucuronidase, Angiogenesis, Heparanase, Isoindole-5-carboxylic acid, Metastasis",

author = "Eddie Mckenzie and Courtney, \{Stephen M.\} and Hay, \{Philip A.\} and Buck, \{Richard T.\} and Colville, \{Claire S.\} and Porter, \{David W.\} and Scopes, \{David I C\} and Pollard, \{Faye C.\} and Page, \{Martin J.\} and Bennett, \{James M.\} and Hircock, \{Margaret L.\} and McKenzie, \{Edward A.\} and Stubberfield, \{Colin R.\} and Turner, \{Paul R.\}",

year = "2004",

month = jun,

day = "21",

doi = "10.1016/j.bmcl.2004.03.086",

language = "English",

volume = "14",

pages = "3269--3273",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "1464-3405",

publisher = "Elsevier BV",

number = "12",

}

Mckenzie, E, Courtney, SM, Hay, PA, Buck, RT, Colville, CS, Porter, DW, Scopes, DIC, Pollard, FC, Page, MJ, Bennett, JM, Hircock, ML, McKenzie, EA, Stubberfield, CR & Turner, PR 2004, '2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: A novel class of small molecule heparanase inhibitors', Bioorganic and Medicinal Chemistry Letters, vol. 14, no. 12, pp. 3269-3273. https://doi.org/10.1016/j.bmcl.2004.03.086

TY - JOUR

T1 - 2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: A novel class of small molecule heparanase inhibitors

AU - Mckenzie, Eddie

AU - Courtney, Stephen M.

AU - Hay, Philip A.

AU - Buck, Richard T.

AU - Colville, Claire S.

AU - Porter, David W.

AU - Scopes, David I C

AU - Pollard, Faye C.

AU - Page, Martin J.

AU - Bennett, James M.

AU - Hircock, Margaret L.

AU - McKenzie, Edward A.

AU - Stubberfield, Colin R.

AU - Turner, Paul R.

PY - 2004/6/21

Y1 - 2004/6/21

N2 - A novel class of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acids are described as inhibitors of the endo-β-glucuronidase heparanase. Several of the compounds, for example, 2-[4-propylamino-5-[5-(4-chloro)phenyl-benzoxazol-2- yl]phenyl]-2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid (9c), display potent heparanase inhibitory activity (IC50 200-500nM) and have high selectivity (>100-fold) over human β-glucuronidase. They also show anti-angiogenic effects. Such compounds should serve as useful biological tools and may provide a basis for the design of novel therapeutic agents. © 2004 Elsevier Ltd. All rights reserved.

AB - A novel class of 2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acids are described as inhibitors of the endo-β-glucuronidase heparanase. Several of the compounds, for example, 2-[4-propylamino-5-[5-(4-chloro)phenyl-benzoxazol-2- yl]phenyl]-2,3-dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid (9c), display potent heparanase inhibitory activity (IC50 200-500nM) and have high selectivity (>100-fold) over human β-glucuronidase. They also show anti-angiogenic effects. Such compounds should serve as useful biological tools and may provide a basis for the design of novel therapeutic agents. © 2004 Elsevier Ltd. All rights reserved.

KW - β-Glucuronidase

KW - Angiogenesis

KW - Heparanase

KW - Isoindole-5-carboxylic acid

KW - Metastasis

U2 - 10.1016/j.bmcl.2004.03.086

DO - 10.1016/j.bmcl.2004.03.086

M3 - Article

SN - 1464-3405

VL - 14

SP - 3269

EP - 3273

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 12

ER -

2,3-Dihydro-1,3-dioxo-1H-isoindole-5-carboxylic acid derivatives: A novel class of small molecule heparanase inhibitors

Abstract

Keywords

Research Beacons, Institutes and Platforms

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