EA022127B1 - Ингибиторы вируса гепатита с - Google Patents

Ингибиторы вируса гепатита с Download PDF

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Publication number
EA022127B1
EA022127B1 EA201370017A EA201370017A EA022127B1 EA 022127 B1 EA022127 B1 EA 022127B1 EA 201370017 A EA201370017 A EA 201370017A EA 201370017 A EA201370017 A EA 201370017A EA 022127 B1 EA022127 B1 EA 022127B1
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methyl
methoxycarbonyl
pyrrolidinyl
carbamate
amino
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EA201370017A
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EA201370017A1 (ru
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Джеффри Ли Ромайн
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Бристол-Майерс Сквибб Компани
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Publication of EA022127B1 publication Critical patent/EA022127B1/ru

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    • 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
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/13—Amines
    • A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
    • A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/4164—1,3-Diazoles
    • A61K31/4178—1,3-Diazoles not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin
    • 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
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    • 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
    • A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
    • A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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    • A61K31/7042—Compounds having saccharide radicals and heterocyclic rings
    • A61K31/7052—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides
    • A61K31/7056—Compounds having saccharide radicals and heterocyclic rings having nitrogen as a ring hetero atom, e.g. nucleosides, nucleotides containing five-membered rings with nitrogen as a ring hetero atom
    • A—HUMAN NECESSITIES
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    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7088—Compounds having three or more nucleosides or nucleotides
    • A61K31/7105—Natural ribonucleic acids, i.e. containing only riboses attached to adenine, guanine, cytosine or uracil and having 3'-5' phosphodiester links
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/2013—IL-2
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/204—IL-6
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/20—Interleukins [IL]
    • A61K38/208—IL-12
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides
    • A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
    • A61K38/19—Cytokines; Lymphokines; Interferons
    • A61K38/21—Interferons [IFN]
    • 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
    • A—HUMAN NECESSITIES
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    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/16—Drugs for disorders of the alimentary tract or the digestive system for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
    • 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
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    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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    • 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

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  • Health & Medical Sciences (AREA)
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Abstract

Изобретение относится к соединениям, композициям и способам лечения гепатита С, вызванного вирусной инфекцией (HCV). Также описаны фармацевтические композиции, содержащие такие соединения, и способы применения этих соединений при лечении HCV инфекции.

Description

(57) Изобретение относится к соединениям, композициям и способам лечения гепатита С, вызванного вирусной инфекцией (НСУ). Также описаны фармацевтические композиции, содержащие такие соединения, и способы применения этих соединений при лечении НСУ инфекции.
022127 Β1
022127 В1
Настоящее изобретение в общем относится к противовирусным соединениям и, более конкретно, к соединениям, которые могут ингибировать функцию белка Ν85Α, кодируемого вирусом гепатита С (НСУ), к композициям, содержащим такие соединения, и способам ингибирования функции белка Ν85Α.
НСУ является одним из основных человеческих патогенов, инфицирующих, по оценкам, 170 млн чел. по всему миру, что примерно в пять раз превышает число инфицированных вирусом иммунодефицита человека типа 1. У значительной части этих инфицированных НСУ индивидуумов развиваются серьезные прогрессирующие заболевания печени, включая цирроз печени и гепатоклеточную карциному.
В настоящее время стандартное лечение гепатита С, при котором применяется комбинация пегилированного интерферона и рибавирина, имеет неоптимальную частоту успеха в достижении устойчивого вирусологического ответа и вызывает многочисленные побочные эффекты. Так что существует очевидная и давно ощущаемая необходимость разработки эффективных методов для решения этой насущной медицинской потребности.

Claims (3)

1. Соединение, выбранное из:
метил (2-(^^)-2-(7-((2-(^^)-1-(^)-2-(4,4-дифторциклогексил)-2((метоксикарбонил)амино)ацетил)-5-метил-2-пирролидинил)-1Н-бензимидазол-5-ил)этинил)-1Ннафто[1,2-ή]имидазол-2-ил)-5-метил-1-пирролидинил)-2-оксо-1-(теΊрагидро-2Н-пиран-4ил)этил)карбамата;
метил ((Ш)-1-((^^)-2-(5-((2-(^^)-1-(((метоксикарбонил)амино)(тетрагидро-2Н-пиран-4ил^цетил^-метил^-пирролидинилрШ-нафто^^-^имидазолО-ил^тинилрШ-бензимидазол^-ил)^метил-1-пирролидинил)карбонил)-2-метилпропил)карбамата;
метил ((Ш)-1-((^^)-2-(5-((2-(^^)-1-(^)-2-((метоксикарбонил)амино)-3-метилбутаноил)-4метил-2-пирролидинил)-1Н-нафто[1,2-ή]имидазол-7-ил)этинил)-1Н-бензимидазол-2-ил)-4-метил-1пирролидинил)карбонил)-2-метилпропил)карбамата;
метил ((Ш)-2-(^^)-2-(7-((2-(^^)-1-(^)-2-((метоксикарбонил)амино)-2-(тетрагидро-2Нпиран-4-ил)ацетил)-4-метил-2-пирролидинил)-1Н-бензимидазол-5-ил)этинил)-1Н-нафто[1,2-ή]имидазол2-ил)-4-метил-1-пирролидинил)-2-оксо-1-(тетрагидро-2Н-пиран-4-ил)этил)карбамата;
метил ((Ш)-1-((^,5К)-3-(5-((2-(^,5К)-2-(^)-2-((метоксикарбонил)амино)-3-метилбутаноил)-5метил-2-азабицикло [3,1,0]гекс-3 -ил)-1Н-нафто [ ^-^имидазолО-ил)этинил)-1Н-бензимидазол-2-ил)-5 метил-2-азабицикло[3,1,0]гекс-2-ил)карбонил)-2-метилпропил)карбамата и метил ((Ш)-2-(^,5К)-3-(7-((2-(^,5К)-2-(^)-2-((метоксикарбонил)амино)-2-(тетрагидро-2Нпиран-4-ил)ацетил)-5-метил-2-азабицикло [3,1,0]гекс-3 -ил)-1Н-бензимидазол-5-ил)этинил)-1Н-нафто [1,2ή]имидазол-2-ил)-5-метил-2-азабицикло[3,1,0]гекс-2-ил)-2-оксо-1-(теΊрагидро-2Н-пиран-4ил)этил)карбамата, или его фармацевтически приемлемая соль.
2. Композиция для ингибирования функции белка ИБ5А, содержащая соединение по п.1 или его фармацевтически приемлемую соль и фармацевтически приемлемый носитель.
3. Способ лечения НСУ инфекции у пациента, включающий введение пациенту терапевтически эффективного количества соединения по п. 1 или его фармацевтически приемлемой соли.
Евразийская патентная организация, ЕАПВ Россия, 109012, Москва, Малый Черкасский пер., 2
EA201370017A 2010-08-04 2010-08-04 Ингибиторы вируса гепатита с EA022127B1 (ru)

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PCT/US2010/044356 WO2012018325A1 (en) 2010-08-04 2010-08-04 Hepatitis c virus inhibitors

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EA022127B1 true EA022127B1 (ru) 2015-11-30

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JP (1) JP5596861B2 (ru)
KR (1) KR20140045903A (ru)
CN (1) CN103153986B (ru)
AU (1) AU2010358561B2 (ru)
BR (1) BR112013002729A2 (ru)
CA (1) CA2807305A1 (ru)
EA (1) EA022127B1 (ru)
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US8552047B2 (en) 2011-02-07 2013-10-08 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US9546160B2 (en) 2011-05-12 2017-01-17 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
EP2709455A4 (en) 2011-05-18 2014-11-05 Enanta Pharm Inc PROCESSES FOR THE PREPARATION OF 5-AZASPIRO [2.4] HEPTANE-6-CARBOXYLIC ACID AND ITS DERIVATIVES
WO2013030750A1 (en) 2011-09-01 2013-03-07 Lupin Limited Antiviral compounds
US9326973B2 (en) 2012-01-13 2016-05-03 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
US9073943B2 (en) 2012-02-10 2015-07-07 Lupin Limited Antiviral compounds with a dibenzooxaheterocycle moiety
CN104302636B (zh) * 2012-04-25 2017-03-29 施万生物制药研发Ip有限责任公司 C型肝炎病毒抑制剂
US9717712B2 (en) 2013-07-02 2017-08-01 Bristol-Myers Squibb Company Combinations comprising tricyclohexadecahexaene derivatives for use in the treatment of hepatitis C virus
US20150023913A1 (en) 2013-07-02 2015-01-22 Bristol-Myers Squibb Company Hepatitis C Virus Inhibitors
JP2016527232A (ja) 2013-07-17 2016-09-08 ブリストル−マイヤーズ スクイブ カンパニーＢｒｉｓｔｏｌ−Ｍｙｅｒｓ Ｓｑｕｉｂｂ Ｃｏｍｐａｎｙ Ｈｃｖの治療に使用するためのビフェニル誘導体を含む組み合わせ
US10617675B2 (en) 2015-08-06 2020-04-14 Bristol-Myers Squibb Company Hepatitis C virus inhibitors
CN110621652A (zh) 2017-05-17 2019-12-27 株式会社德山 二氨基苯化合物的制造方法
GB201803342D0 (en) 2018-03-01 2018-04-18 Medimmune Ltd Methods
GB201806022D0 (en) 2018-04-12 2018-05-30 Medimmune Ltd Pyrrolobenzodiazepines and conjugates thereof
WO2020004043A1 (ja) 2018-06-28 2020-01-02 株式会社トクヤマ α－アジドアニリン誘導体又はα，α'－ジアジド誘導体の製造方法

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WO2002004425A2 (en) * 2000-07-06 2002-01-17 Boehringer Ingelheim (Canada) Ltd. Viral polymerase inhibitors
WO2010096302A1 (en) * 2009-02-17 2010-08-26 Bristol-Myers Squibb Company Hepatitis c virus inhibitors

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SG187183A1 (en) 2013-02-28
JP5596861B2 (ja) 2014-09-24
AU2010358561A1 (en) 2013-03-21
JP2013532725A (ja) 2013-08-19
EA201370017A1 (ru) 2013-05-30
EP2601188B1 (en) 2017-10-18
EP2601188A1 (en) 2013-06-12
CN103153986B (zh) 2014-11-05
CN103153986A (zh) 2013-06-12
CA2807305A1 (en) 2012-02-09
MX337936B (es) 2016-03-29
IL224298A (en) 2015-08-31
BR112013002729A2 (pt) 2016-05-31
AU2010358561B2 (en) 2016-06-02
WO2012018325A1 (en) 2012-02-09

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