WO2008063984A3 - Allosteric modulators of the a1 adenosine receptor - Google Patents

Allosteric modulators of the a1 adenosine receptor Download PDF

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Publication number
WO2008063984A3
WO2008063984A3 PCT/US2007/084490 US2007084490W WO2008063984A3 WO 2008063984 A3 WO2008063984 A3 WO 2008063984A3 US 2007084490 W US2007084490 W US 2007084490W WO 2008063984 A3 WO2008063984 A3 WO 2008063984A3
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WO
WIPO (PCT)
Prior art keywords
adenosine receptor
formula
allosteric modulators
compounds
pain
Prior art date
Application number
PCT/US2007/084490
Other languages
French (fr)
Other versions
WO2008063984A2 (en
Inventor
Pier Giovanni Baraldi
Allan R Moorman
Romeo Romagnoli
Original Assignee
King Pharmaceuticals Res & Dev
Pier Giovanni Baraldi
Allan R Moorman
Romeo Romagnoli
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
Priority claimed from US11/938,465 external-priority patent/US7855209B2/en
Priority claimed from US11/938,514 external-priority patent/US7897596B2/en
Priority to MX2009004763A priority Critical patent/MX2009004763A/en
Priority to JP2009537305A priority patent/JP2010509402A/en
Priority to EP07864306A priority patent/EP2081575A4/en
Priority to KR1020097009765A priority patent/KR20090112627A/en
Application filed by King Pharmaceuticals Res & Dev, Pier Giovanni Baraldi, Allan R Moorman, Romeo Romagnoli filed Critical King Pharmaceuticals Res & Dev
Priority to AU2007323888A priority patent/AU2007323888A1/en
Priority to BRPI0718520-0A priority patent/BRPI0718520A2/en
Priority to CA002669447A priority patent/CA2669447A1/en
Publication of WO2008063984A2 publication Critical patent/WO2008063984A2/en
Publication of WO2008063984A3 publication Critical patent/WO2008063984A3/en
Priority to IL198402A priority patent/IL198402A0/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D333/30—Hetero atoms other than halogen
    • C07D333/36—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/38—Heterocyclic compounds having sulfur as a ring hetero atom
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/08—Antiepileptics; Anticonvulsants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/22—Anxiolytics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/26—Psychostimulants, e.g. nicotine, cocaine
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/04—Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/06—Antiarrhythmics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/08—Bridged systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/10—Spiro-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/10—Spiro-condensed systems
    • C07D491/113—Spiro-condensed systems with two or more oxygen atoms as ring hetero atoms in the oxygen-containing ring

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurosurgery (AREA)
  • Biomedical Technology (AREA)
  • Neurology (AREA)
  • Cardiology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Psychiatry (AREA)
  • Pain & Pain Management (AREA)
  • Hospice & Palliative Care (AREA)
  • Urology & Nephrology (AREA)
  • Vascular Medicine (AREA)
  • Epidemiology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The present invention provides compounds of formula (I) wherein R1, R2, R3, R4 and Q have a meaning as defined herein in the specification. The compounds of formula (I) are allosteric modulators of the A1 adenosine receptor and, thus, may be employed for the treatment of conditions mediated by the A1 adenosine receptor. Accordingly, the compounds of formula (I) may be employed for treatment of pain, in particular, chronic pain such as neuropathic pain; cardiac disease or disorder such as cardiac disarrhythmias, e.g., peroxysmal supraventricular tachycardia, angina, myocardial infarction and stroke; neurological disease or injury; sleep disorder; epilepsy; and depression.
PCT/US2007/084490 2006-11-13 2007-11-13 Allosteric modulators of the a1 adenosine receptor WO2008063984A2 (en)

Priority Applications (8)

Application Number Priority Date Filing Date Title
CA002669447A CA2669447A1 (en) 2006-11-13 2007-11-13 Allosteric modulators of the a1 adenosine receptor
BRPI0718520-0A BRPI0718520A2 (en) 2006-11-13 2007-11-13 COMPOSITION, METHODS FOR ADENOSINE A1 RECEPTOR MODULATION AND FOR THE TREATMENT OF CONDITIONS MEDIATED BY ADENOSINE A1 RECEIVER IN MAMMALS, PHARMACEUTICAL COMPOSITION, AND USES OF A COMPOSITION AND A COMPOUND
JP2009537305A JP2010509402A (en) 2006-11-13 2007-11-13 Allosteric modulator of A1 adenosine receptor
EP07864306A EP2081575A4 (en) 2006-11-13 2007-11-13 Allosteric modulators of the a1 adenosine receptor
KR1020097009765A KR20090112627A (en) 2006-11-13 2007-11-13 Adenosine Modulators of the A1 Adenosine Receptor
MX2009004763A MX2009004763A (en) 2006-11-13 2007-11-13 Allosteric modulators of the a1 adenosine receptor.
AU2007323888A AU2007323888A1 (en) 2006-11-13 2007-11-13 Allosteric modulators of the A1 adenosine receptor
IL198402A IL198402A0 (en) 2006-11-13 2009-04-26 Allosteric modulators of the a1 adenosine receptor

Applications Claiming Priority (6)

Application Number Priority Date Filing Date Title
US85850506P 2006-11-13 2006-11-13
US60/858,505 2006-11-13
US11/938,465 US7855209B2 (en) 2006-11-13 2007-11-12 Allosteric modulators of the A1 adenosine receptor
US11/938,514 2007-11-12
US11/938,465 2007-11-12
US11/938,514 US7897596B2 (en) 2006-11-13 2007-11-12 Allosteric modulators of the A1 adenosine receptor

Publications (2)

Publication Number Publication Date
WO2008063984A2 WO2008063984A2 (en) 2008-05-29
WO2008063984A3 true WO2008063984A3 (en) 2008-08-14

Family

ID=39430473

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2007/084490 WO2008063984A2 (en) 2006-11-13 2007-11-13 Allosteric modulators of the a1 adenosine receptor

Country Status (9)

Country Link
EP (1) EP2081575A4 (en)
JP (1) JP2010509402A (en)
KR (1) KR20090112627A (en)
AU (1) AU2007323888A1 (en)
BR (1) BRPI0718520A2 (en)
CA (1) CA2669447A1 (en)
IL (1) IL198402A0 (en)
MX (1) MX2009004763A (en)
WO (1) WO2008063984A2 (en)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN103739588B (en) * 2014-01-04 2015-07-01 新发药业有限公司 Simple synthesis method of 2-aminothiophene derivative
EP3350182B1 (en) * 2015-09-14 2020-06-03 The National Institute for Biotechnology in the Negev Ltd. Novel piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting vdac oligomerization, apoptosis and mitochondria dysfunction
US10434099B2 (en) 2016-09-22 2019-10-08 The National Institute for Biotechnology in the Negev Ltd. Methods for treating central nervous system disorders using VDAC inhibitors
US10787423B2 (en) 2015-09-14 2020-09-29 The National Institute For Biotechnolgy In The Negev Ltd. Piperazine and piperidine derivatives, their synthesis and use thereof in inhibiting VDAC oligomerization, apoptosis and mitochondria dysfunction
EP3600289A4 (en) 2017-03-21 2020-08-05 Temple University - Of The Commonwealth System of Higher Education 5-hydroxytryptamine receptor 7 modulators and their use as therapeutic agents
EP3600290A4 (en) 2017-03-21 2020-08-12 Temple University - Of The Commonwealth System of Higher Education Novel modulators of the sigma-2 receptor and their method of use

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5332732A (en) * 1992-09-11 1994-07-26 Mcneilab, Inc. Thiophene and pyridine antipsychotic agents
US5750728A (en) * 1992-10-29 1998-05-12 Clariant Gmbh Process for the preparation of aromatic bromomethyl compounds
US5939432A (en) * 1997-10-29 1999-08-17 Medco Research, Inc. Thiophenes useful for modulating the adenosine receptor

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5332732A (en) * 1992-09-11 1994-07-26 Mcneilab, Inc. Thiophene and pyridine antipsychotic agents
US5750728A (en) * 1992-10-29 1998-05-12 Clariant Gmbh Process for the preparation of aromatic bromomethyl compounds
US5939432A (en) * 1997-10-29 1999-08-17 Medco Research, Inc. Thiophenes useful for modulating the adenosine receptor

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
GUTIERREZ-DE-TERAN ET AL.: "Novel approaches for modeling of the A1 adenosine receptor and its agonist binding site", PROTEINS, vol. 54, no. 4, March 2004 (2004-03-01), pages 705 - 715, XP008109385 *

Also Published As

Publication number Publication date
IL198402A0 (en) 2010-02-17
EP2081575A4 (en) 2010-01-06
AU2007323888A1 (en) 2008-05-29
BRPI0718520A2 (en) 2013-11-19
KR20090112627A (en) 2009-10-28
JP2010509402A (en) 2010-03-25
WO2008063984A2 (en) 2008-05-29
EP2081575A2 (en) 2009-07-29
MX2009004763A (en) 2009-05-21
CA2669447A1 (en) 2008-05-29

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