WO2018191642A1 - Novel amodiaquine analogs and methods of uses thereof - Google Patents

Novel amodiaquine analogs and methods of uses thereof Download PDF

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Publication number
WO2018191642A1
WO2018191642A1 PCT/US2018/027528 US2018027528W WO2018191642A1 WO 2018191642 A1 WO2018191642 A1 WO 2018191642A1 US 2018027528 W US2018027528 W US 2018027528W WO 2018191642 A1 WO2018191642 A1 WO 2018191642A1
Authority
WO
WIPO (PCT)
Prior art keywords
compound
quinoline
pharmaceutical composition
mmol
ylamino
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/US2018/027528
Other languages
English (en)
French (fr)
Inventor
Robert A. Davey
Yasuteru SAKURAI
Masanori Baba
Norikazu SAKAKIBARA
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.)
Kagoshima University NUC
Texas Biomedical Research Institute
Original Assignee
Kagoshima University NUC
Texas Biomedical Research Institute
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 Kagoshima University NUC, Texas Biomedical Research Institute filed Critical Kagoshima University NUC
Priority to US16/603,907 priority Critical patent/US11571416B2/en
Priority to JP2019556272A priority patent/JP7176767B2/ja
Publication of WO2018191642A1 publication Critical patent/WO2018191642A1/en
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

Links

Classifications

    • 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
    • A61K31/4706—4-Aminoquinolines; 8-Aminoquinolines, e.g. chloroquine, primaquine
    • 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
    • A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
    • 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
    • A61K31/496—Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
    • 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
    • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
    • A61K31/5375—1,4-Oxazines, e.g. morpholine
    • A61K31/5377—1,4-Oxazines, e.g. morpholine not condensed and containing further heterocyclic rings, e.g. timolol
    • 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
    • A61K31/54—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one sulfur as the ring hetero atoms, e.g. sulthiame
    • A61K31/541—Non-condensed thiazines containing further heterocyclic rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Definitions

  • R2 is bromine. In certain embodiments, R2 is chlorine. In certain embodiments, R2 is iodine.
  • the pharmaceutical composition can include a therapeutically effective amount of a pharmaceutical composition containing a compound of general formula I, and a pharmaceutically acceptable carrier. Also provided herein are methods for treating or preventing a viral infection in a subject by administering to the subject a therapeutically effective amount of a pharmaceutical composition containing a compound of general formula I.
  • the viral infection can be an Ebolavirus infection.
  • the pharmaceutical composition contains 4-(7-iodoquinolin-4-ylamino)-2-diethylaminomethylphenol.
  • Compound 5 (108.5 mg, 0.32 mmol, 64% yield) expressed as Formula VI was obtained as a gray powder using the same procedure as in Example 1, but with the use of diethylamine (881 ⁇ , 8.52 mmol) and 4-chloro-7-fluoroquinoline (95.3 mg, 0.53 mmol) were used instead of dipropargylamine (872 ⁇ , 8.52 mmol) and 4,7-dichloroquinoline (99.0 mg, 0.50 mmol), respectively.
  • the l H NMR data, 13 C NMR data, the HRMS-ESI determination of mass, and melting point of Compound 5 are as follows.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Virology (AREA)
  • Communicable Diseases (AREA)
  • Oncology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Organic Chemistry (AREA)
  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
PCT/US2018/027528 2017-04-13 2018-04-13 Novel amodiaquine analogs and methods of uses thereof Ceased WO2018191642A1 (en)

Priority Applications (2)

Application Number Priority Date Filing Date Title
US16/603,907 US11571416B2 (en) 2017-04-13 2018-04-13 Amodiaquine analogs and methods of uses thereof
JP2019556272A JP7176767B2 (ja) 2017-04-13 2018-04-13 新規なアモジアキン類似体およびその使用方法

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201762485273P 2017-04-13 2017-04-13
US62/485,273 2017-04-13

Publications (1)

Publication Number Publication Date
WO2018191642A1 true WO2018191642A1 (en) 2018-10-18

Family

ID=63792882

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/US2018/027528 Ceased WO2018191642A1 (en) 2017-04-13 2018-04-13 Novel amodiaquine analogs and methods of uses thereof

Country Status (3)

Country Link
US (1) US11571416B2 (https=)
JP (1) JP7176767B2 (https=)
WO (1) WO2018191642A1 (https=)

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3572081A4 (en) * 2017-01-19 2020-10-07 Kagoshima University ANTIVIRAL MEDICINE FOR HIGH FEVER WITH THROMBOCYTOPENIA SYNDROME
WO2021235390A1 (ja) * 2020-05-18 2021-11-25 国立大学法人鹿児島大学 抗ＳＡＲＳ－ＣｏＶ－２薬
EP3960176A1 (en) * 2020-08-26 2022-03-02 DMG Deutsche Malaria GmbH Piperaquine and related drug combinations for use in the treatment of covid-19
WO2023085392A1 (ja) 2021-11-12 2023-05-19 国立大学法人鹿児島大学 抗ＳＡＲＳ－ＣｏＶ－２薬

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060142259A1 (en) * 2004-06-25 2006-06-29 Limin Li Compounds, pharmaceutical compositions and methods for inhibiting HIV infectivity
US20090226401A1 (en) * 2006-02-16 2009-09-10 Deog Joong Kim Methods and compositions for the treatment of parkinson's disease
WO2013138200A1 (en) * 2012-03-13 2013-09-19 Howard University Green chemistry synthesis of the malaria drug amodiaquine and analogs thereof
US20140011837A1 (en) * 2012-07-03 2014-01-09 Justice E. OBI Compositions and methods for treating warts associated with viral infections

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN104703601A (zh) * 2012-07-03 2015-06-10 格雷斯兰生物科技股份有限公司 用于治疗和抑制病毒感染的组合物和方法
AU2015214176A1 (en) * 2014-02-06 2016-09-15 Georgetown University Treating Flavivirus infections with amodiaquine and derivatives thereof
CN110214011A (zh) * 2017-01-19 2019-09-06 国立大学法人鹿儿岛大学 抗严重发热伴血小板减少综合征病毒的药物

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US20060142259A1 (en) * 2004-06-25 2006-06-29 Limin Li Compounds, pharmaceutical compositions and methods for inhibiting HIV infectivity
US20090226401A1 (en) * 2006-02-16 2009-09-10 Deog Joong Kim Methods and compositions for the treatment of parkinson's disease
WO2013138200A1 (en) * 2012-03-13 2013-09-19 Howard University Green chemistry synthesis of the malaria drug amodiaquine and analogs thereof
US20140011837A1 (en) * 2012-07-03 2014-01-09 Justice E. OBI Compositions and methods for treating warts associated with viral infections

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
BERTINARIA ET AL.: "Amodiaquine analogues containing NO -donor substructures: Synthesis and their preliminary evaluation as potential tools in the treatment of cerebral malaria", EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, vol. 46, 22 February 2011 (2011-02-22), pages 1757 - 1767, XP028370944 *
BURCKHALTER ET AL.: "Aminoalkylphenols as Antimalarials. II. (Heterocyclic-amino)-a-amino-o- cresols. The Synthesis of Camoquin", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, vol. 70, April 1948 (1948-04-01), pages 1363 - 1373, XP002230965 *
ZILBERMINTZ ET AL.: "Identification of agents effective against multiple toxins and viruses by host- oriented cell targeting", SCIENTIFIC REPORTS, vol. 5, 21 August 2015 (2015-08-21), pages 1 - 13, XP055554321 *

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP3572081A4 (en) * 2017-01-19 2020-10-07 Kagoshima University ANTIVIRAL MEDICINE FOR HIGH FEVER WITH THROMBOCYTOPENIA SYNDROME
US11001557B2 (en) 2017-01-19 2021-05-11 Kagoshima University Antiviral drug for severe fever with thrombocytopenia syndrome
WO2021235390A1 (ja) * 2020-05-18 2021-11-25 国立大学法人鹿児島大学 抗ＳＡＲＳ－ＣｏＶ－２薬
EP3960176A1 (en) * 2020-08-26 2022-03-02 DMG Deutsche Malaria GmbH Piperaquine and related drug combinations for use in the treatment of covid-19
WO2023085392A1 (ja) 2021-11-12 2023-05-19 国立大学法人鹿児島大学 抗ＳＡＲＳ－ＣｏＶ－２薬

Also Published As

Publication number Publication date
JP2020517603A (ja) 2020-06-18
JP7176767B2 (ja) 2022-11-22
US11571416B2 (en) 2023-02-07
US20200113891A1 (en) 2020-04-16

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