WO2003018004A3 - Analgetic pyrroline derivatives - Google Patents

Analgetic pyrroline derivatives Download PDF

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Publication number
WO2003018004A3
WO2003018004A3 PCT/US2002/027936 US0227936W WO03018004A3 WO 2003018004 A3 WO2003018004 A3 WO 2003018004A3 US 0227936 W US0227936 W US 0227936W WO 03018004 A3 WO03018004 A3 WO 03018004A3
Authority
WO
WIPO (PCT)
Prior art keywords
analgetic
structural analogs
pyrroline derivatives
administration
methadone metabolites
Prior art date
Legal status (The legal status 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 status listed.)
Ceased
Application number
PCT/US2002/027936
Other languages
French (fr)
Other versions
WO2003018004A2 (en
Inventor
Richard Smith-Carliss
Frank S Caruso
Phd Peter Crooks
Kenneth J Kellar
Yingxian Xiao
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Endo Pharmaceuticals Inc
Original Assignee
Endo Pharmaceuticals Inc
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 Endo Pharmaceuticals Inc filed Critical Endo Pharmaceuticals Inc
Priority to JP2003522524A priority Critical patent/JP2005525293A/en
Priority to EP02761550A priority patent/EP1420781A2/en
Priority to AU2002326806A priority patent/AU2002326806B2/en
Priority to CA002458015A priority patent/CA2458015A1/en
Publication of WO2003018004A2 publication Critical patent/WO2003018004A2/en
Publication of WO2003018004A3 publication Critical patent/WO2003018004A3/en
Anticipated expiration legal-status Critical
Priority to US10/501,692 priority patent/US20070129434A1/en
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • C07D207/263—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms
    • C07D207/267—2-Pyrrolidones with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to other ring carbon atoms with only hydrogen atoms or radicals containing only hydrogen and carbon atoms directly attached to the ring nitrogen atom
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • 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
    • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D207/06—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with radicals, containing only hydrogen and carbon atoms, attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/20—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D209/56—Ring systems containing three or more rings
    • C07D209/96—Spiro-condensed ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Engineering & Computer Science (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Neurosurgery (AREA)
  • Epidemiology (AREA)
  • Pain & Pain Management (AREA)
  • Psychiatry (AREA)
  • Addiction (AREA)
  • Rheumatology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

A method for inducing analgesia and/or inhibiting abuse of abusive substances includes administration of d-methadone metabolites or their structural analogs. The d-methadone metabolites, EMDP and EDDP, and their structural analogs may be incorporated into a suitable pharmaceutical composition for administration to patients. The invention includes the method itself, certain structural analogs, and pharmaceutical compositions for use in accordance with the method.
PCT/US2002/027936 2001-08-29 2002-08-29 Analgetic pyrroline derivatives Ceased WO2003018004A2 (en)

Priority Applications (5)

Application Number Priority Date Filing Date Title
JP2003522524A JP2005525293A (en) 2001-08-29 2002-08-29 Analgesics and methods of use
EP02761550A EP1420781A2 (en) 2001-08-29 2002-08-29 Analgetic pyrroline derivatives
AU2002326806A AU2002326806B2 (en) 2001-08-29 2002-08-29 Analgetic pyrroline derivatives
CA002458015A CA2458015A1 (en) 2001-08-29 2002-08-29 Analgetic pyrroline derivatives
US10/501,692 US20070129434A1 (en) 2002-08-29 2004-07-15 Analgesics and methods of use

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US31553001P 2001-08-29 2001-08-29
US60/315,530 2001-08-29

Related Child Applications (1)

Application Number Title Priority Date Filing Date
US10/501,692 Continuation US20070129434A1 (en) 2002-08-29 2004-07-15 Analgesics and methods of use

Publications (2)

Publication Number Publication Date
WO2003018004A2 WO2003018004A2 (en) 2003-03-06
WO2003018004A3 true WO2003018004A3 (en) 2003-05-22

Family

ID=23224847

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2002/027936 Ceased WO2003018004A2 (en) 2001-08-29 2002-08-29 Analgetic pyrroline derivatives

Country Status (6)

Country Link
EP (1) EP1420781A2 (en)
JP (1) JP2005525293A (en)
CN (2) CN1612732A (en)
AU (1) AU2002326806B2 (en)
CA (1) CA2458015A1 (en)
WO (1) WO2003018004A2 (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB915456A (en) * 1959-07-27 1963-01-16 Ernst Boehringer Salts of substituted pyrrolidines and compositions containing them
GB928007A (en) * 1960-06-03 1963-06-06 Ernst Boehringer Substituted pyrrolidines
US3149123A (en) * 1961-01-04 1964-09-15 Parke Davis & Co 1, 3-dialkyl-3-oxyphenylpyrrolidine compounds
GB1401048A (en) * 1971-08-23 1975-07-16 Sandoz Ltd Spiro-indan-1,3-pyrrolidines
US4005103A (en) * 1973-09-27 1977-01-25 Societe Anonyme Dite: Hexachimie Pyrrolidine derivatives

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB915456A (en) * 1959-07-27 1963-01-16 Ernst Boehringer Salts of substituted pyrrolidines and compositions containing them
GB928007A (en) * 1960-06-03 1963-06-06 Ernst Boehringer Substituted pyrrolidines
US3149123A (en) * 1961-01-04 1964-09-15 Parke Davis & Co 1, 3-dialkyl-3-oxyphenylpyrrolidine compounds
GB1401048A (en) * 1971-08-23 1975-07-16 Sandoz Ltd Spiro-indan-1,3-pyrrolidines
US4005103A (en) * 1973-09-27 1977-01-25 Societe Anonyme Dite: Hexachimie Pyrrolidine derivatives

Non-Patent Citations (10)

* Cited by examiner, † Cited by third party
Title
BIOCHEMICAL PHARMACOLOGY (1976), 25(14), 1684-6 *
CAVALLA ET AL.: "Analgetics based on the pyrrolidine ring", J.MED.CHEM., vol. 8, 1964, pages 316 - 326, XP002228897 *
CHEMICAL ABSTRACTS, vol. 86, no. 7, 14 February 1977, Columbus, Ohio, US; abstract no. 37820, BRASE, DAVID A. ET AL: "Comparison of the inhibition of 5-hydroxytryptamine uptake by methadone and its congeners in human platelets" XP002228901 *
CHEMICAL ABSTRACTS, vol. 91, no. 11, 10 September 1979, Columbus, Ohio, US; abstract no. 83167, GORCZYCA, MARIA ET AL: "Synthesis and pharmacological properties of 1,3-substituted and 5-substituted 2-pyrrolidinones" XP002228900 *
POLISH JOURNAL OF PHARMACOLOGY AND PHARMACY (1978), 30(5), 675-83 *
POUPAERT ET AL.: "Structure-Activity Relationships of phenytoin-like anticonvulsant drugs", J.MED.CHEM., vol. 27, 1984, pages 76 - 78, XP002228898 *
RUI X ET AL: "Synthesis and Analgesic Activity of Epibatidine Analogues", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, OXFORD, GB, vol. 6, no. 3, 6 February 1996 (1996-02-06), pages 279 - 282, XP004135077, ISSN: 0960-894X *
TONDER J E ET AL: "AGONISTS AT THE ALPHA4BETA2 NICOTINIC ACETYLCHOLINE RECEPTORS: STRUCTURE-ACTIVITY RELATIONSHIPS AND MOLECULAR MODELLING", CURRENT MEDICINAL CHEMISTRY, BENTHAM SCIENCE PUBLISHERS BV, BE, vol. 8, 2001 - May 2001 (2001-05-01), pages 651 - 674, XP001106484, ISSN: 0929-8673 *
XIAO Y ET AL: "Noncompetitive inhibition of rat alpha3/beta4 neuronal nicotinic acetylcholine receptor (nAChR) function by both enantiomers of methadone, A mu opioid receptor agonist.", SOCIETY FOR NEUROSCIENCE ABSTRACTS., vol. 25, no. 1-2, 1999, 29th Annual Meeting of the Society for Neuroscience.;Miami Beach, Florida, USA; October 23-28, 1999, pages 1240, XP009003070, ISSN: 0190-5295 *
XIAO YINGXIAN ET AL: "Blockade of rat alpha3beta4 nicotinic receptor function by methadone, its metabolites, and structural analogs.", JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, vol. 299, no. 1, October 2001 (2001-10-01), pages 366 - 371, XP002228899, ISSN: 0022-3565 *

Also Published As

Publication number Publication date
EP1420781A2 (en) 2004-05-26
AU2002326806B2 (en) 2007-07-19
CA2458015A1 (en) 2003-03-06
WO2003018004A2 (en) 2003-03-06
JP2005525293A (en) 2005-08-25
CN1612732A (en) 2005-05-04
CN101675926A (en) 2010-03-24

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