Title:
FLUORESCENTLY TAGGED LIGANDS
Document Type and Number:
WIPO Patent Application WO2004088312
Kind Code:
A3
Abstract:
Library comprising a plurality of tagged non-peptide ligands of formula (I): (Lig JL)m L(JT Tag) m (JTL(JLLig)m)p including and salts thereof comprising one or a plurality of same or different ligand moieties Lig each linked to a one or a plurality of same or different tag moieties Tag via same or different linker moieties L and same or different linking site or linking functionality JT and JL wherein Lig comprises a GPCR ligand, an inhibitor of an intracellular enzyme or a substrate or inhibitor of a drug transporter; L is a single bond or is any linking moiety selected from a heteroatom such as N, O, S, P, branched or straight chain saturated or unsaturated, optionally heteroatom containing, CI-600 hydrocarbyl and combinations thereof, which may be monomeric, oligomeric having oligomeric repeat of 2 to 30 or polymeric having polymeric repeat in excess of 30 up to 300; Tag is any known or novel tagging substrate; m are each independently selected from a whole number integer from 1 to 3; p is 0 to 3 characterised in that linking is at same or different linking sites in compounds comprising different Lig, JL, L JT and/or - Tag and is at different linking sites in compounds comprising same Lig, JL, L JT and/or - Tag; process for the preparation thereof; process for the preparation of a library compound of formula (I) or a precursor of formula (IV); method for selecting a compound of formula (I) from a library thereof; compound of formula (I) associated with information relating to its pharmacological properties; a novel compound of formula (I) or precursor of formula (IV); uses thereof; methods for binding or inhibition therewith; use of a fluorescent target therewith; a modified cell surface GPCR and cells expressing the same; and a kit comprising a compound of formula (I) and a target therefor.
Inventors:
GEORGE MICHAEL (GB)
HILL STEPHEN JOHN (GB)
KELLAM BARRIE (GB)
MIDDLETON RICHARD JOHN (GB)
HILL STEPHEN JOHN (GB)
KELLAM BARRIE (GB)
MIDDLETON RICHARD JOHN (GB)
Application Number:
PCT/GB2004/001418
Publication Date:
March 24, 2005
Filing Date:
March 31, 2004
Export Citation:
Assignee:
UNIV NOTTINGHAM (GB)
GEORGE MICHAEL (GB)
HILL STEPHEN JOHN (GB)
KELLAM BARRIE (GB)
MIDDLETON RICHARD JOHN (GB)
GEORGE MICHAEL (GB)
HILL STEPHEN JOHN (GB)
KELLAM BARRIE (GB)
MIDDLETON RICHARD JOHN (GB)
International Classes:
C07D209/56; C07D333/02; C07D473/00; C07H19/16; C07H19/20; G01N33/533; (IPC1-7): G01N33/533; A61K38/25; C07B61/00; C07D209/56; C07D333/02
Foreign References:
| US4774339A | 1988-09-27 | |||
| US5262545A | 1993-11-16 | |||
| US5433896A | 1995-07-18 | |||
| US5451663A | 1995-09-19 | |||
| US5187288A | 1993-02-16 | |||
| US6005113A | 1999-12-21 | |||
| US6054557A | 2000-04-25 | |||
| EP0808829A1 | 1997-11-26 |
Other References:
HEITHIER, HELMUT ET AL: "Synthesis and Properties of Fluorescent .beta.- Adrenoceptor Ligands", BIOCHEMISTRY , CODEN: BICHAW; ISSN: 0006-2960, vol. 33, no. 31, 1994, pages 9126 - 9134, XP002298679
J.C. MCGRATH ET AL: "Viewing adrenoceptors:past, present and future; commentary and a new technique", PHARMACOLOGY COMMUN, vol. 6, no. 1-3, 1995, pages 269 - 279, XP009037236
S.J. BRIDDON ET AL: "Application of fluorescence correlation spectroscopy to the measurement of agonist binding to a G-protein coupled receptor at the single cell level", FARADAY DISCUSSIONS, vol. 126, 12 September 2003 (2003-09-12), pages 197 - 207, XP009037298
J.G. BAKER ET AL: "Pharmacology and direct visualization of BODIPY-TMR-CGP: A long-acting fluorescent beta2-adrenoceptor agonist", BRITISH JOURNAL OF PHARMACOLOGY, vol. 139, no. 2, May 2003 (2003-05-01), pages 232 - 242, XP002298676
S.J. BRIDDON ET AL: "Quantitative analysis of the formation and diffusion of A1-adenosine receptor-antagonist complexes in single living cells", PNAS, vol. 101, no. 13, 16 March 2004 (2004-03-16), pages 4673 - 4678, XP002298677
OAKLEY R H ET AL: "THE CELLULAR DISTRIBUTION OF FLUORESCENTLY LABELED ARRESTINS PROVIDES A ROBUST, SENSITIVE, AND UNIVERSAL ASSAY FOR SCREENING G PROTEIN-COUPLED RECEPTORS", ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES, MARY ANN LIEBERT, NEW YORK, NY, US, vol. 1, no. 1-1, November 2002 (2002-11-01), pages 21 - 30, XP001181634, ISSN: 1540-658X
M.-P- FAURE ET AL: "Synthesis of a biologically active fluorescent probe for labeling neurotensin receptors", THE JOURNAL OF HISTOCHEMISTRY AND CYTOCHEMISTRY, vol. 42, no. 6, 1994, pages 755 - 763, XP002298678
See also references of EP 1623223A2
J.C. MCGRATH ET AL: "Viewing adrenoceptors:past, present and future; commentary and a new technique", PHARMACOLOGY COMMUN, vol. 6, no. 1-3, 1995, pages 269 - 279, XP009037236
S.J. BRIDDON ET AL: "Application of fluorescence correlation spectroscopy to the measurement of agonist binding to a G-protein coupled receptor at the single cell level", FARADAY DISCUSSIONS, vol. 126, 12 September 2003 (2003-09-12), pages 197 - 207, XP009037298
J.G. BAKER ET AL: "Pharmacology and direct visualization of BODIPY-TMR-CGP: A long-acting fluorescent beta2-adrenoceptor agonist", BRITISH JOURNAL OF PHARMACOLOGY, vol. 139, no. 2, May 2003 (2003-05-01), pages 232 - 242, XP002298676
S.J. BRIDDON ET AL: "Quantitative analysis of the formation and diffusion of A1-adenosine receptor-antagonist complexes in single living cells", PNAS, vol. 101, no. 13, 16 March 2004 (2004-03-16), pages 4673 - 4678, XP002298677
OAKLEY R H ET AL: "THE CELLULAR DISTRIBUTION OF FLUORESCENTLY LABELED ARRESTINS PROVIDES A ROBUST, SENSITIVE, AND UNIVERSAL ASSAY FOR SCREENING G PROTEIN-COUPLED RECEPTORS", ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES, MARY ANN LIEBERT, NEW YORK, NY, US, vol. 1, no. 1-1, November 2002 (2002-11-01), pages 21 - 30, XP001181634, ISSN: 1540-658X
M.-P- FAURE ET AL: "Synthesis of a biologically active fluorescent probe for labeling neurotensin receptors", THE JOURNAL OF HISTOCHEMISTRY AND CYTOCHEMISTRY, vol. 42, no. 6, 1994, pages 755 - 763, XP002298678
See also references of EP 1623223A2
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