Title:
ALLOSTERIC SITES ON MUSCARINIC RECEPTORS
Document Type and Number:
WIPO Patent Application WO2001029036
Kind Code:
A3
Abstract:
An allosteric site on muscarinic receptors is disclosed, together with its use for screening for compounds capable of modulating the binding of a primary ligand such as acetylcholine to the receptor. The site is characterised herein a series of indolocarbazoles represented by formula (1) and a series of related compounds represented by formula (2). These compounds are capable of binding to the allosteric site to modulate the binding of a primary ligand to the receptors, showing positive, negative and neutral cooperativity and selectivity for muscarinic receptor subtypes.
Inventors:
BIRDSALL NIGEL (GB)
LAZARENO SEBASTIAN (GB)
LAZARENO SEBASTIAN (GB)
Application Number:
PCT/GB2000/004064
Publication Date:
May 10, 2002
Filing Date:
October 20, 2000
Export Citation:
Assignee:
MEDICAL RES COUNCIL TECHNOLOGY (GB)
BIRDSALL NIGEL (GB)
LAZARENO SEBASTIAN (GB)
BIRDSALL NIGEL (GB)
LAZARENO SEBASTIAN (GB)
International Classes:
G01N33/50; A61K31/437; A61K31/519; A61K31/553; A61K31/569; A61K31/58; A61K45/00; A61P1/04; A61P1/06; A61P1/16; A61P3/10; A61P9/00; A61P11/00; A61P11/06; A61P13/10; A61P17/00; A61P25/10; A61P25/14; A61P25/16; A61P25/18; A61P25/20; A61P25/22; A61P25/24; A61P25/28; A61P27/02; A61P27/06; A61P43/00; C07D471/04; C07D487/04; C07D498/22; C07J7/00; C07J71/00; G01N33/15; G01N33/566; G01N33/94; (IPC1-7): G01N33/566; A61K31/395
Domestic Patent References:
| WO1996003377A1 | 1996-02-08 | |||
| WO1996013506A1 | 1996-05-09 |
Foreign References:
| GB2292685A | 1996-03-06 | |||
| US5747336A | 1998-05-05 | |||
| US5677327A | 1997-10-14 | |||
| US5658898A | 1997-08-19 |
Other References:
BIRDSALL NIGEL J M ET AL: "Subtype-selective positive cooperative interactions between brucine analogs and acetylcholine at muscarinic receptors: Functional studies.", MOLECULAR PHARMACOLOGY, vol. 55, no. 4, April 1999 (1999-04-01), pages 778 - 787, XP000997267, ISSN: 0026-895X
LAZARENO S ET AL: "Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: Radioligand binding studies.", MOLECULAR PHARMACOLOGY, vol. 53, no. 3, March 1998 (1998-03-01), pages 573 - 589, XP000997226, ISSN: 0026-895X
LAZARENO SEBASTIAN ET AL: "Detection, quantitation and verification of allosteric interactions of agents with labeled and unlabeled ligands at G protein-coupled receptors: Interactions of strychnine and acetylcholine at muscarinic receptors.", MOLECULAR PHARMACOLOGY, vol. 48, no. 2, 1995, pages 362 - 378, XP000997227, ISSN: 0026-895X
LAZARENO S ET AL: "Allosteric effects of four stereoisomers of a fused indole ring system with 3H-N-methylscopolamine and acetylcholine at M1-M4 muscarinic receptors.", LIFE SCIENCES, vol. 64, no. 6-7, 8 January 1999 (1999-01-08), Eighth International Symposium on Subtypes of Muscarinic Receptors;Danvers, Massachusetts, USA; August 25-29, 1998, pages 519 - 526, XP000997312, ISSN: 0024-3205
LAZARENO SEBASTIAN ET AL: "Allosteric interactions of staurosporine and other indolocarbazoles with N-(methyl-3H)scopolamine and acetylcholine at muscarinic receptor subtypes: Identification of a second allosteric site.", MOLECULAR PHARMACOLOGY, vol. 58, no. 1, July 2000 (2000-07-01), pages 194 - 206, XP000997198, ISSN: 0026-895X
LAZARENO S ET AL: "Subtype-selective positive cooperative interactions between brucine analogues and acetylcholine at muscarinic receptors: Radioligand binding studies.", MOLECULAR PHARMACOLOGY, vol. 53, no. 3, March 1998 (1998-03-01), pages 573 - 589, XP000997226, ISSN: 0026-895X
LAZARENO SEBASTIAN ET AL: "Detection, quantitation and verification of allosteric interactions of agents with labeled and unlabeled ligands at G protein-coupled receptors: Interactions of strychnine and acetylcholine at muscarinic receptors.", MOLECULAR PHARMACOLOGY, vol. 48, no. 2, 1995, pages 362 - 378, XP000997227, ISSN: 0026-895X
LAZARENO S ET AL: "Allosteric effects of four stereoisomers of a fused indole ring system with 3H-N-methylscopolamine and acetylcholine at M1-M4 muscarinic receptors.", LIFE SCIENCES, vol. 64, no. 6-7, 8 January 1999 (1999-01-08), Eighth International Symposium on Subtypes of Muscarinic Receptors;Danvers, Massachusetts, USA; August 25-29, 1998, pages 519 - 526, XP000997312, ISSN: 0024-3205
LAZARENO SEBASTIAN ET AL: "Allosteric interactions of staurosporine and other indolocarbazoles with N-(methyl-3H)scopolamine and acetylcholine at muscarinic receptor subtypes: Identification of a second allosteric site.", MOLECULAR PHARMACOLOGY, vol. 58, no. 1, July 2000 (2000-07-01), pages 194 - 206, XP000997198, ISSN: 0026-895X
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