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WO2010091104A8 - Glucosylceramide synthase inhibitors - Google Patents

Glucosylceramide synthase inhibitors Download PDF

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Publication number
WO2010091104A8
WO2010091104A8 PCT/US2010/023080 US2010023080W WO2010091104A8 WO 2010091104 A8 WO2010091104 A8 WO 2010091104A8 US 2010023080 W US2010023080 W US 2010023080W WO 2010091104 A8 WO2010091104 A8 WO 2010091104A8
Authority
WO
WIPO (PCT)
Prior art keywords
glucosylceramide synthase
gcs
compounds
pharmaceutically acceptable
acceptable salts
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/US2010/023080
Other languages
French (fr)
Other versions
WO2010091104A1 (en
Inventor
Wai Ki Vicky Chan
Hongwang Du
Patrick Kearney
Elena S. Koltun
Jason August Nachtigall
Kevin Noson
Michael Pack
Steven James Richards
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.)
Exelixis Inc
Original Assignee
Exelixis 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 Exelixis Inc filed Critical Exelixis Inc
Priority to ARP100100326A priority Critical patent/AR075367A1/en
Priority to TW099103670A priority patent/TW201040156A/en
Publication of WO2010091104A1 publication Critical patent/WO2010091104A1/en
Publication of WO2010091104A8 publication Critical patent/WO2010091104A8/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen 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
    • C07D213/62—Oxygen or sulfur atoms
    • C07D213/63—One oxygen atom
    • C07D213/64—One oxygen atom attached in position 2 or 6
    • C07D213/643—2-Phenoxypyridines; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P3/00—Drugs for disorders of the metabolism
    • A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
    • A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • 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
    • 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
    • C07D401/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D405/12—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 linked by a chain containing hetero atoms as chain links
    • 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
    • C07D405/14—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 three or more hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen 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
    • 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
    • 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

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Engineering & Computer Science (AREA)
  • Diabetes (AREA)
  • Obesity (AREA)
  • Hematology (AREA)
  • Endocrinology (AREA)
  • Cardiology (AREA)
  • Emergency Medicine (AREA)
  • Urology & Nephrology (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Vascular Medicine (AREA)
  • Immunology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

The present invention comprises glucosylceramide synthase (GCS) inhibitors of structural formula (I), and pharmaceutically acceptable salts thereof, wherein R1, E, A, L, X1, Q, R4, R5, m and n, are as defined herein, as well as N-oxides of them and pharmaceutically acceptable salts thereof. The invention further comprises composition comprising the compounds, N-oxides, and/or pharmaceutically acceptable salts thereof. The invention also comprises use of the compounds and compositions for treating diseases in which GCS is a mediator or is implicated. The invention also comprises use of the compounds in and for the manufacture of medicaments, particularly for treating diseases in which GCS is a mediator or is implicated.
PCT/US2010/023080 2009-02-06 2010-02-03 Glucosylceramide synthase inhibitors Ceased WO2010091104A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
ARP100100326A AR075367A1 (en) 2009-02-06 2010-02-05 GLUCOSILCERAMIDE SINTASA INHIBITORS
TW099103670A TW201040156A (en) 2009-02-06 2010-02-06 Glucosylceramide synthase inhibitors

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US15043409P 2009-02-06 2009-02-06
US61/150,434 2009-02-06

Publications (2)

Publication Number Publication Date
WO2010091104A1 WO2010091104A1 (en) 2010-08-12
WO2010091104A8 true WO2010091104A8 (en) 2011-04-07

Family

ID=42148396

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2010/023080 Ceased WO2010091104A1 (en) 2009-02-06 2010-02-03 Glucosylceramide synthase inhibitors

Country Status (3)

Country Link
AR (1) AR075367A1 (en)
TW (1) TW201040156A (en)
WO (1) WO2010091104A1 (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108864076A (en) * 2012-09-11 2018-11-23 建新公司 glucosylceramide synthase inhibitors

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
LT2685986T (en) 2011-03-18 2020-03-10 Genzyme Corporation GLYCOSYL CERAMIDE SYNTHETIC INHIBITOR
JO3713B1 (en) * 2013-03-15 2021-01-31 Genzyme Corp SALT FORMS OF (S)-Quinuclidin-3-yl (2-(2-(4-fluorophenyl)thiazol-4-yl)propan-2-yl)carbamate
EP3318277A1 (en) 2016-11-04 2018-05-09 Institut du Cerveau et de la Moelle Epiniere-ICM Inhibitors of glucosylceramide synthase for the treatment of motor neuron diseases
WO2021096238A1 (en) * 2019-11-15 2021-05-20 Yuhan Corporation Novel derivatives having 2,3-dihydro-1h-indene or 2,3-dihydrobenzofuran moiety or pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
ES2982711T3 (en) * 2019-11-15 2024-10-17 Yuhan Corp Derivatives having a 1,2,3,4-tetrahydronaphthalene moiety or a pharmaceutically acceptable salt thereof and pharmaceutical compositions comprising the same
TW202142236A (en) 2020-02-03 2021-11-16 美商健臻公司 Methods for treating neurological symptoms associated with lysosomal storage diseases
EP4142878B1 (en) 2020-04-28 2024-06-26 The Regents of The University of Michigan Pyridine inhibitors of glucosylceramide synthase and therapeutic methods using the same
AU2021311131A1 (en) 2020-07-24 2023-03-23 Genzyme Corporation Pharmaceutical compositions comprising venglustat
EP4213843A4 (en) * 2020-09-17 2024-09-11 Merck Sharp & Dohme LLC MODIFIED IMIDAZOPYRIDINES AS GLUCOSYLCERAMIDE SYNTHASE INHIBITORS
US20230391758A1 (en) * 2020-09-18 2023-12-07 Merck Sharp & Dohme Llc Modified benzofuran-carboxamides as glucosylceramide synthase inhibitors
EP4490148A2 (en) * 2022-03-11 2025-01-15 Merck Sharp & Dohme LLC Non-aromatic cyclic-pyrimidine analogs as glucosylceramide synthase inhibitors
US20250171467A1 (en) * 2022-03-14 2025-05-29 Merck Sharp & Dohme Llc Fused pyrazole amide analogs as glucosylceramide synthase inhibitors

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4107288A (en) 1974-09-18 1978-08-15 Pharmaceutical Society Of Victoria Injectable compositions, nanoparticles useful therein, and process of manufacturing same
US5145684A (en) 1991-01-25 1992-09-08 Sterling Drug Inc. Surface modified drug nanoparticles
GB0400812D0 (en) 2004-01-14 2004-02-18 Celltech R&D Ltd Novel compounds
EP1811991B1 (en) 2004-11-10 2018-11-07 Genzyme Corporation Treatment of type 2 diabetes using inhibitors of glycosphingolipid synthesis
ES2277745B1 (en) * 2005-06-14 2008-06-01 Laboratorios Almirall S.A. N-AMIDA DERIVATIVES OF 8-AZABICICLO /3.2.1/OCT-3-ILO AS AN ANTIGONISTS OF CCR1.
EP2594562B1 (en) * 2007-05-31 2016-07-20 Genzyme Corporation 2-acylaminopropanol-type glucosylceramide synthase inhibitors

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108864076A (en) * 2012-09-11 2018-11-23 建新公司 glucosylceramide synthase inhibitors
CN108864076B (en) * 2012-09-11 2022-02-11 建新公司 Glucosylceramide synthase inhibitors

Also Published As

Publication number Publication date
WO2010091104A1 (en) 2010-08-12
TW201040156A (en) 2010-11-16
AR075367A1 (en) 2011-03-30

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