WO2012008999A3 - Tricyclic compounds as allosteric modulators of metabotropic glutamate receptors - Google Patents

Tricyclic compounds as allosteric modulators of metabotropic glutamate receptors Download PDF

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Publication number
WO2012008999A3
WO2012008999A3 PCT/US2011/001201 US2011001201W WO2012008999A3 WO 2012008999 A3 WO2012008999 A3 WO 2012008999A3 US 2011001201 W US2011001201 W US 2011001201W WO 2012008999 A3 WO2012008999 A3 WO 2012008999A3
Authority
WO
WIPO (PCT)
Prior art keywords
methyl
independently
metabotropic glutamate
glutamate receptors
allosteric modulators
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/US2011/001201
Other languages
French (fr)
Other versions
WO2012008999A2 (en
Inventor
Nigel J. Liverton
Christelle Bolea
Sylvain Celanire
Luo Yunfu
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.)
Addex Pharmaceuticals SA
Organon Pharma UK Ltd
Merck Sharp and Dohme LLC
Original Assignee
Addex Pharmaceuticals SA
Merck Sharp and Dohme Ltd
Merck Sharp and Dohme LLC
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 Addex Pharmaceuticals SA, Merck Sharp and Dohme Ltd, Merck Sharp and Dohme LLC filed Critical Addex Pharmaceuticals SA
Priority to EP11807173.7A priority Critical patent/EP2595996A2/en
Priority to US13/809,579 priority patent/US20130210807A1/en
Publication of WO2012008999A2 publication Critical patent/WO2012008999A2/en
Anticipated expiration legal-status Critical
Publication of WO2012008999A3 publication Critical patent/WO2012008999A3/en
Ceased legal-status Critical Current

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
    • C07D513/04—Ortho-condensed systems
    • 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
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/433—Thidiazoles
    • 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
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic 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
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
    • C07D513/12—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains three hetero rings
    • C07D513/14—Ortho-condensed systems

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  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Medicinal Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

The present invention describes and claims compounds of the Structural Formula I, Structural Formula II, or Structural Formula III: wherein R1, R2, R3 and R3' are -H or methyl, or R3 and R3 taken together form a double bond, or R3' is -H and R2 and R3 taken together form a spiro-cyclopropyl substituent, R4 is -H or -F, and R5 is -H, methyl, -CI or -Br, Formula II wherein R1 is -H, ethyl-, isopropyl-, cyclopropyl-, methyl- or methoxy-, R4 is -H or -F, and "Y" is: (a) -CH2-; (b) -CR6H-0-CR7R8-, wherein R6, R7, and R8 are independently - H or methyl; (c) -CR6H-N(R9)-CR7R8-, wherein R6, R7, and R8 are independently -H or methyl; (d) -CH2-C(R9)(R10)-C(R7)(R8)-, wherein R7, R8, R9 and R10 are independently - H or -methyl, or both R7 and R8 are -F, R9 and R10 are independently -H or -methyl, or both R9 and R10 are -F, or R9 and R10 taken together are (0=), which together with the carbon to which they are attached forms a carbonyl group.
PCT/US2011/001201 2010-07-14 2011-07-09 Tricyclic compounds as allosteric modulators of metabotropic glutamate receptors Ceased WO2012008999A2 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
EP11807173.7A EP2595996A2 (en) 2010-07-14 2011-07-09 Tricyclic compounds as allosteric modulators of metabotropic glutamate receptors
US13/809,579 US20130210807A1 (en) 2010-07-14 2011-07-09 Tricyclic Compounds as Allosteric Modulators of Metabotropic Glutamate Receptors.

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US36419510P 2010-07-14 2010-07-14
US61/364,195 2010-07-14

Publications (2)

Publication Number Publication Date
WO2012008999A2 WO2012008999A2 (en) 2012-01-19
WO2012008999A3 true WO2012008999A3 (en) 2014-03-27

Family

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Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2011/001201 Ceased WO2012008999A2 (en) 2010-07-14 2011-07-09 Tricyclic compounds as allosteric modulators of metabotropic glutamate receptors

Country Status (3)

Country Link
US (1) US20130210807A1 (en)
EP (1) EP2595996A2 (en)
WO (1) WO2012008999A2 (en)

Families Citing this family (27)

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EP2593277A4 (en) * 2010-07-14 2014-09-03 Addex Pharmaceuticals Sa NOVEL FOUNDED PYRAZOLE DERIVATIVES AND THEIR USE AS ALLOSTERIC MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS
US8754114B2 (en) 2010-12-22 2014-06-17 Incyte Corporation Substituted imidazopyridazines and benzimidazoles as inhibitors of FGFR3
ES2704744T3 (en) 2012-06-13 2019-03-19 Incyte Holdings Corp Substituted tricyclic compounds as FGFR inhibitors
US9388185B2 (en) 2012-08-10 2016-07-12 Incyte Holdings Corporation Substituted pyrrolo[2,3-b]pyrazines as FGFR inhibitors
US9266892B2 (en) 2012-12-19 2016-02-23 Incyte Holdings Corporation Fused pyrazoles as FGFR inhibitors
EA035095B1 (en) 2013-04-19 2020-04-27 Инсайт Холдингс Корпорейшн Bicyclic heterocycles as fgfr inhibitors
US10851105B2 (en) 2014-10-22 2020-12-01 Incyte Corporation Bicyclic heterocycles as FGFR4 inhibitors
MX373169B (en) 2015-02-20 2020-04-24 Incyte Holdings Corp Bicyclic heterocycles as fgfr inhibitors
MA41551A (en) 2015-02-20 2017-12-26 Incyte Corp BICYCLIC HETEROCYCLES USED AS FGFR4 INHIBITORS
WO2016134294A1 (en) 2015-02-20 2016-08-25 Incyte Corporation Bicyclic heterocycles as fgfr4 inhibitors
CN108299302A (en) * 2017-01-11 2018-07-20 西南科技大学 A kind of new method preparing 3- acetyl pyrazoles
AR111960A1 (en) 2017-05-26 2019-09-04 Incyte Corp CRYSTALLINE FORMS OF A FGFR INHIBITOR AND PROCESSES FOR ITS PREPARATION
MA52493A (en) 2018-05-04 2021-03-10 Incyte Corp FGFR INHIBITOR SALTS
CR20200590A (en) 2018-05-04 2021-04-26 Incyte Corp Solid forms of an fgfr inhibitor and processes for preparing the same
WO2020185532A1 (en) 2019-03-08 2020-09-17 Incyte Corporation Methods of treating cancer with an fgfr inhibitor
WO2021007269A1 (en) 2019-07-09 2021-01-14 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
WO2021067374A1 (en) 2019-10-01 2021-04-08 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
TWI891666B (en) 2019-10-14 2025-08-01 美商英塞特公司 Bicyclic heterocycles as fgfr inhibitors
WO2021076728A1 (en) 2019-10-16 2021-04-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
BR112022010664A2 (en) 2019-12-04 2022-08-16 Incyte Corp DERIVATIVES OF A FGFR INHIBITOR
EP4069696A1 (en) 2019-12-04 2022-10-12 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
WO2021146424A1 (en) 2020-01-15 2021-07-22 Incyte Corporation Bicyclic heterocycles as fgfr inhibitors
TW202304459A (en) 2021-04-12 2023-02-01 美商英塞特公司 Combination therapy comprising an fgfr inhibitor and a nectin-4 targeting agent
WO2022261159A1 (en) 2021-06-09 2022-12-15 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
EP4352059A1 (en) 2021-06-09 2024-04-17 Incyte Corporation Tricyclic heterocycles as fgfr inhibitors
CN114380747B (en) * 2021-11-26 2024-04-05 上海毕得医药科技股份有限公司 Synthesis method of 3-acetyl pyrazole
WO2025057723A1 (en) 2023-09-13 2025-03-20 石原産業株式会社 N–substituted oxyamide compound or salt thereof

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GB0900404D0 (en) * 2009-01-12 2009-02-11 Addex Pharmaceuticals Sa New compounds 4

Patent Citations (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
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Non-Patent Citations (2)

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KEMPSON ET AL.: "Fused pyrimidine based inhibitors of phosphodiesterase 7 (PDE7):synthesis and initial structure-activity relationships.", BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol. 15, no. 7, 2005, pages 1829 - 1833, XP027800906 *

Also Published As

Publication number Publication date
EP2595996A2 (en) 2013-05-29
WO2012008999A2 (en) 2012-01-19
US20130210807A1 (en) 2013-08-15

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