WO2010091104A8 - Inhibiteurs de la glucosylcéramide synthase - Google Patents

Inhibiteurs de la glucosylcéramide synthase 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
Application number
PCT/US2010/023080
Other languages
English (en)
Other versions
WO2010091104A1 (fr
Inventor
Wai Ki Vicky Chan
Hongwang Du
Patrick Kearney
Elena S. Koltun
Jason August Nachtigall
Kevin Noson
Michael Pack
Steven James Richards
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/es
Priority to TW099103670A priority patent/TW201040156A/zh
Publication of WO2010091104A1 publication Critical patent/WO2010091104A1/fr
Publication of WO2010091104A8 publication Critical patent/WO2010091104A8/fr

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    • 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

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  • 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

La présente invention porte sur des inhibiteurs de la glucosylcéramide synthase (GCS) de formule structurale (I) et sur les sels pharmaceutiquement acceptables de ceux-ci, formule dans laquelle R1, E, A, L, X1, Q, R4, R5, m et n sont tels que définis ici, ainsi que sur les N-oxydes de ceux-ci et sur leurs sels pharmaceutiquement acceptables. L'invention porte en outre sur une composition comprenant les composés, les N-oxydes et/ou les sels pharmaceutiquement acceptables. L'invention porte également sur l'utilisation des composés et des compositions pour traiter des maladies dans lesquelles la GCS est un médiateur ou est impliquée. L'invention porte aussi sur l'utilisation des composés dans et pour la fabrication de médicaments, en particulier pour traiter des maladies dans lesquelles la GCS est un médiateur ou est impliquée.
PCT/US2010/023080 2009-02-06 2010-02-03 Inhibiteurs de la glucosylcéramide synthase WO2010091104A1 (fr)

Priority Applications (2)

Application Number Priority Date Filing Date Title
ARP100100326A AR075367A1 (es) 2009-02-06 2010-02-05 Inhibidores de glucosilceramida sintasa
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 (fr) 2010-08-12
WO2010091104A8 true WO2010091104A8 (fr) 2011-04-07

Family

ID=42148396

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2010/023080 WO2010091104A1 (fr) 2009-02-06 2010-02-03 Inhibiteurs de la glucosylcéramide synthase

Country Status (3)

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

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108864076A (zh) * 2012-09-11 2018-11-23 建新公司 葡糖神经酰胺合酶抑制剂

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
RU2018104472A (ru) * 2011-03-18 2019-02-22 Джензим Корпорейшн Ингибиторы глюкозилцерамид-синтазы
JO3713B1 (ar) 2013-03-15 2021-01-31 Genzyme Corp أشكال ملح (s)-كوينوكليدين-3-يل(2-(2-(4-فلوروفينيل)ثيازول-4-يل)بروبان-2-يل)كارباميت
EP3318277A1 (fr) 2016-11-04 2018-05-09 Institut du Cerveau et de la Moelle Epiniere-ICM Inhibiteurs de la synthase de glucosylcéramide pour le traitement de maladies du motoneurone
WO2021096239A1 (fr) * 2019-11-15 2021-05-20 Yuhan Corporation Nouveaux dérivés ayant une fraction 1,2,3,4-tétrahydronaphtalène ou un sel pharmaceutiquement acceptable de ceux-ci et compositions pharmaceutiques les comprenant
AU2020384066A1 (en) * 2019-11-15 2022-04-21 Green Cross 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
US20230212123A1 (en) 2020-04-28 2023-07-06 The Regents Of The University Of Michigan Pyridine Inhibitors of Glucosylceramide Synthase and Therapeutic Methods Using the Same
KR20230043024A (ko) 2020-07-24 2023-03-30 젠자임 코포레이션 벤글루스타트를 포함하는 제약 조성물
WO2023172475A2 (fr) * 2022-03-11 2023-09-14 Merck Sharp & Dohme Llc Analogues de pyrimidine cycliques non aromatiques utilisés en tant qu'inhibiteurs de glucosylcéramide synthase
WO2023177563A2 (fr) * 2022-03-14 2023-09-21 Merck Sharp & Dohme Llc Analogues de pyrazole amide fusionnés utilisés en tant qu'inhibiteurs de glucosylcéramide synthase

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
US8003617B2 (en) 2004-11-10 2011-08-23 Genzyme Corporation Methods of treating diabetes mellitus
ES2277745B1 (es) * 2005-06-14 2008-06-01 Laboratorios Almirall S.A. Derivados n-amida de 8-azabiciclo /3.2.1/oct-3-ilo como antagonistas de ccr1.
EP2594564B1 (fr) * 2007-05-31 2016-09-28 Genzyme Corporation Inhibiteurs de glucosylcéramide synthase de type 2-acylaminopropanol

Cited By (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN108864076A (zh) * 2012-09-11 2018-11-23 建新公司 葡糖神经酰胺合酶抑制剂
CN108864076B (zh) * 2012-09-11 2022-02-11 建新公司 葡糖神经酰胺合酶抑制剂

Also Published As

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

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