WO2016196393A3 - Autophagy-inhibiting compounds and uses thereof - Google Patents

Autophagy-inhibiting compounds and uses thereof Download PDF

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Publication number
WO2016196393A3
WO2016196393A3 PCT/US2016/034887 US2016034887W WO2016196393A3 WO 2016196393 A3 WO2016196393 A3 WO 2016196393A3 US 2016034887 W US2016034887 W US 2016034887W WO 2016196393 A3 WO2016196393 A3 WO 2016196393A3
Authority
WO
WIPO (PCT)
Prior art keywords
autophagy
inhibiting compounds
compound
compounds
cancer
Prior art date
Application number
PCT/US2016/034887
Other languages
French (fr)
Other versions
WO2016196393A2 (en
Inventor
Thomas DECKWERTH
Edward Kleinman
Fuqiang Ruan
William Baker
Richard Klinghoffer
Original Assignee
Presage Biosciences, 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 Presage Biosciences, Inc. filed Critical Presage Biosciences, Inc.
Priority to GB1718875.6A priority Critical patent/GB2555270A/en
Publication of WO2016196393A2 publication Critical patent/WO2016196393A2/en
Publication of WO2016196393A3 publication Critical patent/WO2016196393A3/en

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Classifications

    • 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
    • C07D401/14—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 three or more hetero 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
    • A61K31/435—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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/4709—Non-condensed quinolines 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
    • A61K31/435—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
    • A61K31/47—Quinolines; Isoquinolines
    • A61K31/472—Non-condensed isoquinolines, e.g. papaverine
    • A61K31/4725—Non-condensed isoquinolines, e.g. papaverine 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
    • A61K31/495—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
    • A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
    • 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
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/38—Nitrogen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/38—Nitrogen atoms
    • C07D215/40—Nitrogen atoms attached in position 8
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
    • C07D215/38—Nitrogen atoms
    • C07D215/42—Nitrogen atoms attached in position 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
    • C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 nitrogen-containing ring
    • 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
    • C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
    • C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
    • 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

Landscapes

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

Abstract

The present disclosure describes a compound for use in the treatment of cancer, infectious disease, and autoimmune disorders. The compounds herein can inhibit autophagy in an affected cell to promote cell death. Further, the compound can be used to overcome the drug-resistance of certain cells.
PCT/US2016/034887 2015-05-29 2016-05-27 Autophagy-inhibiting compounds and uses thereof WO2016196393A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
GB1718875.6A GB2555270A (en) 2015-05-29 2016-05-27 Autophagy-inhibiting compounds and uses thereof

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US201562168291P 2015-05-29 2015-05-29
US62/168,291 2015-05-29
US201662304125P 2016-03-04 2016-03-04
US62/304,125 2016-03-04

Publications (2)

Publication Number Publication Date
WO2016196393A2 WO2016196393A2 (en) 2016-12-08
WO2016196393A3 true WO2016196393A3 (en) 2017-05-18

Family

ID=57441838

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2016/034887 WO2016196393A2 (en) 2015-05-29 2016-05-27 Autophagy-inhibiting compounds and uses thereof

Country Status (2)

Country Link
GB (1) GB2555270A (en)
WO (1) WO2016196393A2 (en)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3533451B1 (en) 2017-01-21 2022-07-27 Guangzhou Hanfang Pharmaceuticals Co., Ltd. Application of paeoniflorin-6'-o-benzene sulfonate in medicine for treating sjögren's syndrome
CA3154678A1 (en) * 2019-09-18 2021-03-25 The Regents Of The University Of California Biaminoquinolines and nanoformulations for cancer treatment
JP2023513793A (en) * 2020-02-14 2023-04-03 ソーク インスティテュート フォー バイオロジカル スタディーズ Macrocyclic ULK1/2 inhibitor

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006051489A1 (en) * 2004-11-10 2006-05-18 Institut National De La Sante Et De La Recherche Medicale (Inserm) Use of 1,4-bis (3-aminoalkyl) piperazine derivatives in the treatment of neurodegenerative diseases
WO2012149186A2 (en) * 2011-04-29 2012-11-01 The Trustees Of The University Of Pennsylvania Novel bisaminoquinoline compounds, pharmaceutical compositions prepared therefrom and their use

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2006051489A1 (en) * 2004-11-10 2006-05-18 Institut National De La Sante Et De La Recherche Medicale (Inserm) Use of 1,4-bis (3-aminoalkyl) piperazine derivatives in the treatment of neurodegenerative diseases
WO2012149186A2 (en) * 2011-04-29 2012-11-01 The Trustees Of The University Of Pennsylvania Novel bisaminoquinoline compounds, pharmaceutical compositions prepared therefrom and their use

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
HEERDEN, L. V. ET AL.: "Synthesis and in vitro antimalarial activity of a series of bisquinoline and bispyrrolo[1,2a]quinoxaline compounds", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 55, 2012, pages 335 - 345, XP055141266 *
MCAFEE, Q. ET AL.: "Autophagy inhibitor Lys05 has single-agent antitumor activity and reproduces the phenotype of a genetic autophagy deficiency", PNAS, vol. 109, no. 21, 22 May 2012 (2012-05-22), pages 8253 - 8258, XP055166131 *
ZHANG, H. ET AL.: "Synthesis and in vitro cytotoxicity evaluation of 4-amino quinoline derivatives", BIOMEDICINE & PHARMACOTHERAPY, vol. 62, no. 2, 2008, pages 65 - 69, XP022475873 *

Also Published As

Publication number Publication date
WO2016196393A2 (en) 2016-12-08
GB2555270A (en) 2018-04-25
GB201718875D0 (en) 2017-12-27

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