WO2005021547A3 - Heterocyclic cannabinoid cb2 receptor antagonists - Google Patents

Heterocyclic cannabinoid cb2 receptor antagonists Download PDF

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Publication number
WO2005021547A3
WO2005021547A3 PCT/US2004/027809 US2004027809W WO2005021547A3 WO 2005021547 A3 WO2005021547 A3 WO 2005021547A3 US 2004027809 W US2004027809 W US 2004027809W WO 2005021547 A3 WO2005021547 A3 WO 2005021547A3
Authority
WO
WIPO (PCT)
Prior art keywords
dihydro
morpholinoethyl
benzamide
chloro
compounds
Prior art date
Application number
PCT/US2004/027809
Other languages
French (fr)
Other versions
WO2005021547A2 (en
Inventor
William B Cowden
Darren R March
Alan Robertson
Natalie Jenkins
Original Assignee
Pharmaxis Pty Ltd
William B Cowden
Darren R March
Alan Robertson
Natalie Jenkins
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 Pharmaxis Pty Ltd, William B Cowden, Darren R March, Alan Robertson, Natalie Jenkins filed Critical Pharmaxis Pty Ltd
Publication of WO2005021547A2 publication Critical patent/WO2005021547A2/en
Publication of WO2005021547A3 publication Critical patent/WO2005021547A3/en

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D235/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings
    • C07D235/02—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, condensed with other rings condensed with carbocyclic rings or ring systems
    • C07D235/04—Benzimidazoles; Hydrogenated benzimidazoles
    • C07D235/24—Benzimidazoles; Hydrogenated benzimidazoles 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 in position 2
    • C07D235/30—Nitrogen atoms not forming part of a nitro radical
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/36—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems
    • C07D241/38—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings condensed with carbocyclic rings or ring systems with only hydrogen or carbon atoms directly attached to the ring nitrogen atoms
    • C07D241/40—Benzopyrazines
    • C07D241/44—Benzopyrazines 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 carbon atoms of the hetero ring

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

Novel selective cannabinoid CB2 receptor ligands, primarily agonists, have a number of biological and pharmacological activities, including bronchial action, immunomodulatory action and analgesia. Hence, they are useful for treating diseases or conditions characterized by pain, inflammation and immunological dysregulation. Examples of this class of novel compounds are 4 chloro-N-[1-(2-morpholin-4-ylethyl)-1H-benzimidazol-2-yl]benzamide and 4-chloro-N-[7 methoxy-1-(2-morpholin-4-ylethyl)-1H-benzimidazol-2-yl]benzamide. Other examples of the novel compounds are 4-derivatives of 3-amino and 3-carboxy-1,2-dihydro-1-substitutedquinazol-2-ones, including 2-chloro-N (1,2-dihydro-1-(2-morpholinoethyl)-2-oxoquinoxalin-3-yl)benzamide, 3-chloro-N-(1,2-dihydro-1-(2-morpholinoethyl)-2-oxoquinoxalin-3-yl)benzamide, tert-butyl 1,2-dihydro-1-(2-morpholinoethyl)-2-oxoquinoxalin-3-ylcarbamate and N-benzyl-3,4-dihydro-4-(2-morpholinoethyl)-3-oxoquinoxaline-2-carboxamide. The compounds bind specifically to a cell-bound or cell-free CB2 receptor with an affinity (Kd) ≤ 100 µM. As agonists, these compounds stimulate a CB2-related post-binding signal transduction event, e.g., inhibition of adenylyl cyclase activity, after binding to a CB2 receptor on a cell. These compounds are used to treat inflammatory conditions, cell proliferative disorders, or an immune disorder, and may be administered in combination with agents that are also useful for the treatment of the symptoms or cause of the underlying disease or condition.
PCT/US2004/027809 2003-08-28 2004-08-27 Heterocyclic cannabinoid cb2 receptor antagonists WO2005021547A2 (en)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US49828803P 2003-08-28 2003-08-28
US60/498,288 2003-08-28
US54177704P 2004-02-05 2004-02-05
US60/541,777 2004-02-05

Publications (2)

Publication Number Publication Date
WO2005021547A2 WO2005021547A2 (en) 2005-03-10
WO2005021547A3 true WO2005021547A3 (en) 2005-08-18

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2004/027809 WO2005021547A2 (en) 2003-08-28 2004-08-27 Heterocyclic cannabinoid cb2 receptor antagonists

Country Status (1)

Country Link
WO (1) WO2005021547A2 (en)

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SE0302573D0 (en) 2003-09-26 2003-09-26 Astrazeneca Ab Benzimidazole derivatives, compositions containing them, preparation thereof and uses thereof
CA2544191A1 (en) 2003-11-04 2005-05-26 Merck & Co., Inc. Substituted naphthyridinone derivatives
US20060025448A1 (en) * 2004-07-22 2006-02-02 Cadila Healthcare Limited Hair growth stimulators
WO2006033627A1 (en) * 2004-09-24 2006-03-30 Astrazeneca Ab Compounds, compositions containing them, preparation thereof and uses thereof iiii
MX2007003105A (en) 2004-09-24 2007-06-07 Aztrazeneca Ab Benzimidazole derivatives, compositions containing them, preparation thereof and uses thereof i.
CA2582512A1 (en) * 2004-09-24 2006-03-30 Astrazeneca Ab Compounds, compositions containing them, preparations thereof and uses thereof ii
ATE493391T1 (en) 2005-03-15 2011-01-15 Pfizer BENZIMIDAZOLONE DERIVATIVES AS CB2 RECEPTOR LIGANDS
TW200745049A (en) * 2006-03-23 2007-12-16 Astrazeneca Ab New crystalline forms
TW200808769A (en) 2006-04-18 2008-02-16 Astrazeneca Ab Therapeutic compounds
US7601716B2 (en) 2006-05-01 2009-10-13 Cephalon, Inc. Pyridopyrazines and derivatives thereof as ALK and c-Met inhibitors
US20090325936A1 (en) * 2006-12-20 2009-12-31 Bilodeau Mark T Imidazopyridine analogs as cb2 receptor modulators, useful in the treatment of pain, respiratory and non-respiratory diseases
US9193713B2 (en) * 2007-10-12 2015-11-24 Abbvie Inc. Compounds as cannabinoid receptor ligands
CA2718402C (en) 2008-03-05 2017-08-22 Merck Patent Gmbh Pyridopyrazinones derivatives insulin secretion stimulators, methods for obtaining them and use thereof for the treatment of diabetes
BRPI1013620B1 (en) 2009-06-26 2018-05-22 Kumiai Chemical Industry Co., Ltd. METHOD FOR PRODUCING KETOMALONIC ACID COMPOUND
JP5795635B2 (en) 2010-08-05 2015-10-14 アムジェン インコーポレイテッド Benzimidazole and azabenzimidazole compounds that inhibit anaplastic lymphoma kinase
WO2014145852A2 (en) 2013-03-15 2014-09-18 Knopp Biosciences Llc Imidazo(4,5-b) pyridin-2-yl amides as kv7 channel activators
JP5921500B2 (en) 2013-07-19 2016-05-24 イハラケミカル工業株式会社 Method for producing ketomalonic acid compound
KR102134407B1 (en) 2014-02-17 2020-07-15 구미아이 가가쿠 고교 가부시키가이샤 Method for continuously producing ketomalonic acid compound using flow reactor
EP3572405B9 (en) 2014-09-12 2023-12-06 Biohaven Therapeutics Ltd. Benzoimidazol-1,2-yl amides as kv7 channel activators
CN107973755B (en) * 2018-01-08 2020-12-29 滨州学院 Preparation method of 3-acetamido quinoxalinone derivative
EP3643303A1 (en) * 2018-10-22 2020-04-29 InnovativeHealth Group SL Compounds for use in the treatment or prevention of fibrotic diseases; pharmaceutical, cosmetic compositions and uses thereof
WO2020232350A1 (en) * 2019-05-15 2020-11-19 The Regents Of The University Of Colorado, A Body Corporate Assays for synthetic cannabinoids

Citations (7)

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US4002623A (en) * 1974-08-07 1977-01-11 Pfizer Inc. Anti-inflammatory 1-[3-(dialkylamino)propyl]-2-acylaminobenzimidazoles and 2-acylamino-3-[3-(dialkylamino)-propyl]imidazo[4,5-b]pyridines
JPS6233158A (en) * 1985-08-02 1987-02-13 Shionogi & Co Ltd Benzimidazole derivative and antiulcer agent
FR2731707A1 (en) * 1995-03-13 1996-09-20 Synthelabo Novel 2-imidazolyl alkylamino benzimidazole(s)
WO2000018767A2 (en) * 1998-09-30 2000-04-06 Neurogen Corporation 2-piperazino alkylamino benzoazole derivatives: dopamine receptor subtype specific ligands
EP1048655A1 (en) * 1997-12-03 2000-11-02 Taisho Pharmaceutical Co., Ltd 1,2-dihydro-2-oxoquinoline derivatives
WO2001000611A1 (en) * 1999-06-28 2001-01-04 Janssen Pharmaceutica N.V. Respiratory syncytial virus replication inhibitors
WO2002085866A1 (en) * 2001-04-20 2002-10-31 Astrazeneca Ab Novel compounds

Patent Citations (7)

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Publication number Priority date Publication date Assignee Title
US4002623A (en) * 1974-08-07 1977-01-11 Pfizer Inc. Anti-inflammatory 1-[3-(dialkylamino)propyl]-2-acylaminobenzimidazoles and 2-acylamino-3-[3-(dialkylamino)-propyl]imidazo[4,5-b]pyridines
JPS6233158A (en) * 1985-08-02 1987-02-13 Shionogi & Co Ltd Benzimidazole derivative and antiulcer agent
FR2731707A1 (en) * 1995-03-13 1996-09-20 Synthelabo Novel 2-imidazolyl alkylamino benzimidazole(s)
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Non-Patent Citations (2)

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Title
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PATENT ABSTRACTS OF JAPAN vol. 0112, no. 14 (C - 434) 10 July 1987 (1987-07-10) *

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