EA027280B1 - Сульфамоил-ариламиды и их применение в качестве лекарственных препаратов для лечения гепатита b - Google Patents
Сульфамоил-ариламиды и их применение в качестве лекарственных препаратов для лечения гепатита b Download PDFInfo
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- EA027280B1 EA027280B1 EA201590450A EA201590450A EA027280B1 EA 027280 B1 EA027280 B1 EA 027280B1 EA 201590450 A EA201590450 A EA 201590450A EA 201590450 A EA201590450 A EA 201590450A EA 027280 B1 EA027280 B1 EA 027280B1
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- Prior art keywords
- alkyl
- group
- independently selected
- saturated ring
- halogen
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- C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
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- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
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- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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Abstract
Сульфамоил-ариламиды и их применение в качестве лекарственных препаратов для лечения гепатита В. Ингибиторы репликации HBV формулы (I), в том числе их стереохимические изомерные формы, а также их соли, гидраты, сольваты, где В, R, Rи Rимеют значения, определенные в настоящем документе. Настоящее изобретение также относится к способам получения указанных соединений, содержащих их фармацевтических композиций, а также к их применению отдельно или в комбинации с другими ингибиторами HBV в терапии, активной в отношении HBV.
Description
С071) 277/16 (2006.01) (54) СУЛЬФАМОИЛ-АРИЛАМИДЫ И ИХ ПРИМЕНЕНИЕ В КАЧЕСТВЕ ЛЕКАРСТВЕННЫХ ПРЕПАРАТОВ ДЛЯ ЛЕЧЕНИЯ ГЕПАТИТА В
027280 Β1 (31) 12182076.5; 12185055.6; 12190837.0; 13157230.7; 13169574.4 (32) 2012.08.28; 2012.09.19; 2012.10.31; 2013.02.28; 2013.05.28 (33) ЕР (43) 2015.07.30 (86) РСТ/ЕР2013/067829 (87) \\О 2014/033176 2014.03.06 (71) (73) Заявитель и патентовладелец:
ЯНССЕН САЙЕНСИЗ АЙРЛЭНД ЮСи (ΙΕ)
Claims (12)
- ФОРМУЛА ИЗОБРЕТЕНИЯ или его стереоизомерная или таутомерная форма, где В представляет собой моноциклическое 5-6-членное ароматическое кольцо, необязательно содержащее один или несколько гетероатомов, каждый из которых независимо выбран из группы, состоящей из О, З и Ν, при этом такое 5-6-членное ароматическое кольцо необязательно замещено одним или несколькими заместителями, каждый из которых независимо выбран из группы, состоящей из водорода, галогена, С‘-С3алкила, СИ СРН2, СР2Н и СР3;Κ1 представляет собой водород;Κ2 представляет собой С‘-С6алкил, С‘-С6алкенил, С^С^лкил-И^ С(=О)-И5, СРН2, СР2Н, СР3, дигидроинденильный или тетрагидронафталенильный фрагмент, необязательно замещенный ОН, или 3-7членное насыщенное кольцо, необязательно содержащее один или несколько гетероатомов, каждый из которых независимо выбран из группы, состоящей из О, З и Ν, где каждый из 3-7-членного насыщенного кольца, С^С^лкил-Ю или С‘-С6алкила замещен одним или несколькими заместителями, каждый из которых независимо выбран из группы, состоящей из галогена, С‘-С4алкилокси, С‘-С4алкилоксикарбонила, оксо, С(=О)-С‘-С3алкила, С‘-С4алкила, СП СРН2, СР2Н и СР3; илиΚ1 и Κ2 вместе с атомом азота, к которому они присоединены, образуют 6-10-членное бициклическое или мостиковое кольцо или 5-7-членное насыщенное кольцо, при этом такой фрагмент бициклического, мостикового или насыщенного кольца необязательно содержит один или несколько дополнительных гетероатомов, каждый из которых независимо выбран из группы, состоящей из О, З и Ν, и где 5-7членное насыщенное кольцо замещено одним или несколькими заместителями, каждый из которых независимо выбран из группы, состоящей из галогена, С‘-С4алкилоксикарбонила, оксо, С(=О)-С‘-С3алкила, С‘-С4алкила, ΟΝ, СРН2, СР2Н и СР3;каждый Κ4 независимо выбран из водорода, галогена, С‘-С4алкилокси, С‘-С4алкила, С‘-С4алкенила, ОН, С^ СРН2, СР2Н, СР3, НС=С и 3-5-членного насыщенного кольца, необязательно содержащего один или несколько гетероатомов, каждый из которых независимо выбран из группы, состоящей из О и Ν, где С‘-С4алкил необязательно замещен ОН и где по меньшей мере один Κ4 представляет собой фтор, а другой Κ4 выбран из группы, состоящей из С‘-С3алкила, С‘-С3алкенила, СНР2 или циклопропила;Κ5 представляет собой С‘-С6алкил, СРН2, СР2Н, СР3, фенил, пиридил или 3-7-членное насыщенное кольцо, необязательно содержащее один или несколько гетероатомов, каждый из которых независимо выбран из группы, состоящей из О, З и Ν, при этом такое 3-7-членное насыщенное кольцо необязательно замещено одним или несколькими заместителями, каждый из которых независимо выбран из группы, состоящей из галогена, С‘-С4алкилокси, С‘-С4алкилоксикарбонила, оксо, С(=О)-С‘-С3алкила, С‘С4алкила, ОН, ΟΝ, СРН2, СР2Н и СР3.
- 2. Соединение по п.1, где один Κ4 представляет собой фтор, а другой Κ4 выбран из группы, состоящей из метила или СНР2, и где указанный фтор находится в пара-положении, а указанный метил или СНР2 находится в мета-положении относительно азота(*).
- 3. Соединение по любому из пп.1, 2, где Κ2 представляет собой 4-7-членное насыщенное кольцо, содержащее атом углерода и один или несколько атомов кислорода, при этом такое 4-7-членное насыщенное кольцо замещено одним или несколькими заместителями, каждый из которых независимо выбран из группы, состоящей из галогена, С‘-С4алкилокси, С‘-С4алкилоксикарбонила, С(=О)-С‘-С3алкила, С‘-С4алкила, ΟΝ, СРН2, СР2Н и СР3.
- 4. Соединение по любому из пп.1-3, где Κ2 представляет собой 4-7-членное насыщенное кольцо, содержащее атом углерода и один или несколько атомов кислорода, при этом такое 4-7-членное насыщенное кольцо замещено одним или несколькими заместителями, каждый из которых независимо выбран из группы, состоящей из галогена, С‘-С4алкилоксикарбонила, С(=О)-С‘-С3алкила, С‘-С4алкила, С^ СРН2, СР2Н и СР3.
- 5. Соединение по любому из предыдущих пунктов, где В представляет собой фенил или тиофен, необязательно замещенный одним или несколькими заместителями, каждый из которых независимо выбран из группы, состоящей из галогена, С‘-С3алкила, С^ СРН2, СР2Н и СР3.
- 6. Соединение по любому из предыдущих пунктов, которое представлено формулой (Ш)- 92 027280 где Κ1, Κ2, Κ4 определены в любом из предыдущих пунктов и Κ3 выбран из группы, состоящей из водорода, галогена, С1-С3алкила, ΟΝ, СЕН2, СЕ2Н и СЕ3.
- 7. Соединение по любому из пп.1-3, которое представлено формулой (Ιά) где Κ1, Κ2, Κ4 определены в любом из предыдущих пунктов и Κ3 выбран из группы, состоящей из водорода, галогена, С1-С3алкила, ΟΝ, СЕН2, СЕ2Н, СЕ3.
- 8. Соединение по п.5 или 6, где Κ3 представляет собой водород.
- 9. Соединение по любому из предыдущих пунктов, которое представлено формулой (1с) где Κ1, Κ2, Κ4 определены в любом из предыдущих пунктов.
- 10. Применение соединения по любому из предыдущих пунктов в предупреждении или лечении инфекции НВУ у млекопитающего.
- 11. Фармацевтическая композиция, обладающая способностью ингибировать НВУ, содержащая терапевтически эффективное количество соединения по любому из пп.1-8 и фармацевтически приемлемый носитель.
- 12. Композиция, содержащая:(a) соединение формулы (I) по любому из пп.1-8 и (b) ингибитор НВУ, выбранный из интерферона-α (1ЕЫ-а), пегилированного интерферона-α, 3ТС и адефовира, причем указанная композиция пригодна в виде комбинированного препарата для одновременного, раздельного или последовательного применения в лечении инфекций, вызываемых НВУ.
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