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WO2001029036A3 - Allosteric sites on muscarinic receptors - Google Patents

Allosteric sites on muscarinic receptors Download PDF

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Publication number
WO2001029036A3
WO2001029036A3 PCT/GB2000/004064 GB0004064W WO0129036A3 WO 2001029036 A3 WO2001029036 A3 WO 2001029036A3 GB 0004064 W GB0004064 W GB 0004064W WO 0129036 A3 WO0129036 A3 WO 0129036A3
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WO
WIPO (PCT)
Prior art keywords
binding
muscarinic receptors
allosteric sites
receptors
compounds
Prior art date
Application number
PCT/GB2000/004064
Other languages
French (fr)
Other versions
WO2001029036A2 (en
Inventor
Nigel Birdsall
Sebastian Lazareno
Original Assignee
Medical Res Council Technology
Nigel Birdsall
Sebastian Lazareno
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Medical Res Council Technology, Nigel Birdsall, Sebastian Lazareno filed Critical Medical Res Council Technology
Priority to CA002386149A priority Critical patent/CA2386149A1/en
Priority to AU10383/01A priority patent/AU779391B2/en
Priority to JP2001531835A priority patent/JP2003512607A/en
Priority to EP00971543A priority patent/EP1222463A2/en
Publication of WO2001029036A2 publication Critical patent/WO2001029036A2/en
Publication of WO2001029036A3 publication Critical patent/WO2001029036A3/en

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
    • G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
    • G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
    • G01N33/94—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing involving narcotics or drugs or pharmaceuticals, neurotransmitters or associated receptors
    • G01N33/9406—Neurotransmitters
    • G01N33/944—Acetylcholine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/04—Drugs for disorders of the alimentary tract or the digestive system for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
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    • A—HUMAN NECESSITIES
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    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
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    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
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    • A61P25/00—Drugs for disorders of the nervous system
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    • G01N2333/435—Assays involving biological materials from specific organisms or of a specific nature from animals; from humans
    • G01N2333/705—Assays involving receptors, cell surface antigens or cell surface determinants
    • G01N2333/70571—Assays involving receptors, cell surface antigens or cell surface determinants for neuromediators, e.g. serotonin receptor, dopamine receptor
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N2500/00—Screening for compounds of potential therapeutic value

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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.
PCT/GB2000/004064 1999-10-21 2000-10-20 Allosteric sites on muscarinic receptors WO2001029036A2 (en)

Priority Applications (4)

Application Number Priority Date Filing Date Title
CA002386149A CA2386149A1 (en) 1999-10-21 2000-10-20 Allosteric sites on muscarinic receptors
AU10383/01A AU779391B2 (en) 1999-10-21 2000-10-20 Allosteric sites on muscarinic receptors
JP2001531835A JP2003512607A (en) 1999-10-21 2000-10-20 Allosteric site of muscarinic receptor
EP00971543A EP1222463A2 (en) 1999-10-21 2000-10-20 Allosteric sites on muscarinic receptors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GBGB9924962.5A GB9924962D0 (en) 1999-10-21 1999-10-21 Allosteric sites on muscarinic receptors
GB9924962.5 1999-10-21

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US09/886,882 Continuation US6382257B2 (en) 1999-10-20 2001-06-21 Fluid control system

Publications (2)

Publication Number Publication Date
WO2001029036A2 WO2001029036A2 (en) 2001-04-26
WO2001029036A3 true WO2001029036A3 (en) 2002-05-10

Family

ID=10863158

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB2000/004064 WO2001029036A2 (en) 1999-10-21 2000-10-20 Allosteric sites on muscarinic receptors

Country Status (6)

Country Link
EP (1) EP1222463A2 (en)
JP (1) JP2003512607A (en)
AU (1) AU779391B2 (en)
CA (1) CA2386149A1 (en)
GB (1) GB9924962D0 (en)
WO (1) WO2001029036A2 (en)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7504509B2 (en) 2003-12-19 2009-03-17 Plexxikon, Inc. Compounds and methods for development of Ret modulators
US8865735B2 (en) 2011-02-21 2014-10-21 Hoffman-La Roche Inc. Solid forms of a pharmaceutically active substance
US9096593B2 (en) 2009-11-06 2015-08-04 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US9150570B2 (en) 2012-05-31 2015-10-06 Plexxikon Inc. Synthesis of heterocyclic compounds
US9169250B2 (en) 2006-11-22 2015-10-27 Plexxikon Inc. Compounds modulating c-fms and/or c-kit activity and uses therefor
US9447089B2 (en) 2009-04-03 2016-09-20 Plexxikon Inc. Compositions and uses thereof
US9469640B2 (en) 2007-07-17 2016-10-18 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2004084889A1 (en) * 2003-03-28 2004-10-07 Pfizer Inc. Use of protein kinase c inhibitor for suppressing sustained slow postsynaptic excitation (sspe) of enteric neurons
PT1696931E (en) 2003-12-22 2009-06-12 Acadia Pharm Inc Amino substituted diaryl[a,d]cycloheptene analogs as muscarinic agonists and methods of treatment of neuropsychiatric disorders
PT1807434E (en) * 2004-10-25 2010-09-22 Lilly Co Eli Thienopyridines as allosteric potentiators of the m4 muscarinic receptor
WO2007002670A2 (en) * 2005-06-28 2007-01-04 Bausch & Lomb Incorporated Method of lowering intraocular pressure
BR112013020041B1 (en) 2011-02-07 2021-11-23 Plexxikon, Inc COMPOUNDS AND COMPOSITIONS FOR THE MODULATION OF KINASES AND THEIR USE

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1996003377A1 (en) * 1994-07-27 1996-02-08 Sankyo Company, Limited Heterocyclic compounds, useful as allosteric effectors at muscarinic receptors
GB2292685A (en) * 1994-07-27 1996-03-06 Sankyo Co Allosteric effectors at muscarinic receptors
WO1996013506A1 (en) * 1994-10-26 1996-05-09 Cephalon, Inc. Protein kinase inhibitors for treatment of neurological disorders
US5658898A (en) * 1994-11-09 1997-08-19 Ciba Geigy Corporation Intravenous solutions for a derivative of staurosporine
US5677327A (en) * 1995-06-22 1997-10-14 Allergan Method for identifying muscarinic agents lacking miotic side effects
US5747336A (en) * 1988-09-08 1998-05-05 The United States Of America As Represented By The Department Of Health And Human Services Cloned human genes for muscarinic acetylcholine receptors and cells lines expressing same

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5747336A (en) * 1988-09-08 1998-05-05 The United States Of America As Represented By The Department Of Health And Human Services Cloned human genes for muscarinic acetylcholine receptors and cells lines expressing same
WO1996003377A1 (en) * 1994-07-27 1996-02-08 Sankyo Company, Limited Heterocyclic compounds, useful as allosteric effectors at muscarinic receptors
GB2292685A (en) * 1994-07-27 1996-03-06 Sankyo Co Allosteric effectors at muscarinic receptors
WO1996013506A1 (en) * 1994-10-26 1996-05-09 Cephalon, Inc. Protein kinase inhibitors for treatment of neurological disorders
US5658898A (en) * 1994-11-09 1997-08-19 Ciba Geigy Corporation Intravenous solutions for a derivative of staurosporine
US5677327A (en) * 1995-06-22 1997-10-14 Allergan Method for identifying muscarinic agents lacking miotic side effects

Non-Patent Citations (5)

* Cited by examiner, † Cited by third party
Title
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: "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 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: "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 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 *

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7504509B2 (en) 2003-12-19 2009-03-17 Plexxikon, Inc. Compounds and methods for development of Ret modulators
US9169250B2 (en) 2006-11-22 2015-10-27 Plexxikon Inc. Compounds modulating c-fms and/or c-kit activity and uses therefor
US9487515B2 (en) 2006-11-22 2016-11-08 Plexxikon Inc. Compounds modulating c-fms and/or c-kit activity and uses therefor
US9469640B2 (en) 2007-07-17 2016-10-18 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US9447089B2 (en) 2009-04-03 2016-09-20 Plexxikon Inc. Compositions and uses thereof
US9096593B2 (en) 2009-11-06 2015-08-04 Plexxikon Inc. Compounds and methods for kinase modulation, and indications therefor
US8865735B2 (en) 2011-02-21 2014-10-21 Hoffman-La Roche Inc. Solid forms of a pharmaceutically active substance
US9150570B2 (en) 2012-05-31 2015-10-06 Plexxikon Inc. Synthesis of heterocyclic compounds

Also Published As

Publication number Publication date
CA2386149A1 (en) 2001-04-26
AU779391B2 (en) 2005-01-20
WO2001029036A2 (en) 2001-04-26
JP2003512607A (en) 2003-04-02
EP1222463A2 (en) 2002-07-17
AU1038301A (en) 2001-04-30
GB9924962D0 (en) 1999-12-22

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