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RU2016132858A - Производные фторнафтила - Google Patents

Производные фторнафтила Download PDF

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RU2016132858A
RU2016132858A RU2016132858A RU2016132858A RU2016132858A RU 2016132858 A RU2016132858 A RU 2016132858A RU 2016132858 A RU2016132858 A RU 2016132858A RU 2016132858 A RU2016132858 A RU 2016132858A RU 2016132858 A RU2016132858 A RU 2016132858A
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fluoro
methyl
naphthamide
hydroxytetrahydro
pyran
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RU2016132858A
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Цбинден Катрин Грёбке
Эмманюэль Пинар
Томас Рикманс
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Ф. Хоффманн-Ля Рош Аг
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    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/335Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435Heterocyclic 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
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    • A61K31/435Heterocyclic 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
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    • C07D213/02Heterocyclic 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
    • C07D213/04Heterocyclic 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
    • C07D213/60Heterocyclic 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
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    • C07D309/08Heterocyclic compounds containing six-membered rings having one oxygen atom as the only ring hetero atom, not condensed with other rings having no double bonds between ring members or between ring members and non-ring members 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
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    • C07D401/04Heterocyclic 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 directly linked by a ring-member-to-ring-member bond
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    • C07DHETEROCYCLIC COMPOUNDS
    • C07D405/00Heterocyclic 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
    • C07D405/14Heterocyclic 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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Claims (46)

1. Соединение формулы I
Figure 00000001
где:
R1 представляет собой С4-6-циклоалкил или С4-6-гетероциклоалкил, которые необязательно замещены одним или двумя заместителями, выбранными из гидроксила или низшего алкила;
А представляет собой фенил, пиридинил или пиперидинил;
R2 представляет собой атом водорода, атом галогена, низший алкил, цианогруппу, С4-6-циклоалкил, низшую алкоксигруппу, низшую алкоксигруппу, замещенную галогеном или является пяти- или шестичленной гетероарильной группой, необязательно замещенной низшей алкильной группой;
n равно 1 или 2;
или его фармацевтически приемлемая соль присоединения кислоты, рацемическая смесь или соответствующий энантиомер и/или оптический изомер.
2. Соединение формулы I по п. 1, отличающееся тем, что А представляет собой фенил, а другие заместители являются такими, как определено в п. 1.
3. Соединение формулы I, выбранное из:
1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-4-(4-метилбензил)-2-нафтамид;
4-бензил-1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-2-нафтамид;
4-(4-хлорбензил)-1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-2-нафтамид;
4-(4-цианобензил)-1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-2-нафтамид;
1-фтор-4-(2-фтор-4-(1-метил-1Н-пиразол-4-ил)бензил)-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-2-нафтамид;
1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-4-(4-(трифторметокси)бензил)-2-нафтамид или
1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-4-(4-(1-метил-1Н-пиразол-4-ил)бензил)-2-нафтамид.
4. Соединение формулы I по п. 1, отличающееся тем, что А представляет собой пиридинил, а другие заместители являются такими, как определено в п. 1.
5. Соединение формулы I выбранное из:
4-((6-хлорипиридин-3-ил)метил)-1-фтор-N-((1SR,2SR)-2-гидроксициклогексил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((1S,2S)-2-гидроксициклогексил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((3S,4S)-4-гидрокситетрагидро-2Н-пиран-3-ил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((1S,2S)-2-гидроксициклопентил)-2-нафтамид;
4-((6-хлорипиридин-3-ил)метил)-1-фтор-N-((1S,2R)-2-гидроксициклопентил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((1SR,2SR)-2-гидрокси-2-метилциклогексил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((1SR,2RS)-2-гидрокси-2-метилциклогексил)-2-нафтамид;
4-((6-хлорпиридин-3-ил)метил)-1-фтор-N-((1SR,2RS)-2-гидроксициклогексил)-2-нафтамид;
1-фтор-N-((1S,2S)-2-гидроксициклогексил)-4-((6-(1-метил-1Н-пиразол-4-ил)пиридин-3-ил)метил)-2-нафтамид;
1-фтор-N-((3RS,4SR)-3-гидрокситетрагидро-2Н-пиран-4-ил)-4-((6-(1-метил-1Н-пиразол-4-ил)пиридин-3-ил)метил)-2-нафтамид;
1-фтор-N-[(3S,4R)-3-гидрокситетрагидропиран-4-ил]-4-[[6-(1-метилпиразол-4-ил)-3-пиридил]метил]нафталин-2-карбоксамид;
1-фтор-N-[(3R,4S)-3-гидрокситетрагидропиран-4-ил]-4-[[6-(1-метилпиразол-4-ил)-3-пиридил]метил]нафталин-2-карбоксамид;
1-фтор-N-((3S,4S)-4-гидрокситетрагидро-2Н-пиран-3-ил)-4-((6-(1-метил-1Н-пиразол-4-ил)пиридин-3-ил)метил)-2-нафтамид;
1-фтор-N-((1SR,2RS)-2-гидрокси-2-метилциклогексил)-4-((6-(1-метил-1Н-пиразол-4-ил)пиридин-3-ил)метил)-2-нафтамид;
1-фтор-N-((1SR,2SR)-2-гидроксициклогексил)-4-((6-метилпиридин-3-ил)метил)-2-нафтамид;
4-((6-циклопропилпиридин-3-ил)метил)-1-фтор-N-((1S,2S)-2-гидроксициклогексил)-2-нафтамид;
4-[(6-хлорпиридин-3-ил)метил]-1-фтор-N-[(3S,4R)-3-гидроксиоксан-4-ил]нафталин-2-карбоксамид.
6. Соединение формулы I по п. 1, отличающееся тем, что А представляет собой пиперидинил, а другие заместители являются такими, как определено в п. 1.
7. Соединение формулы I по п. 6, отличающееся тем, что этим соединением является 4-((4-циано-4-(пиридин-2-ил)пиперидин-1-ил)метил)-1-фтор-N-((1S,2S)-2-гидроксициклогексил)-2-нафтамид.
8. Фармацевтическая композиция, содержащая соединение по любому из пп. 1-7 и фармацевтически приемлемый носитель и/или адъювант.
9. Фармацевтическая композиция, содержащая соединение по любому из пп. 1-7 и фармацевтически приемлемый носитель и/или адъювант для применения для лечения болезни Альцгеймера, когнитивных нарушений, шизофрении, болей или нарушений сна.
10. Соединения по любому из пп. 1-7 для применения в качестве терапевтически активных веществ.
11. Соединения по любому из пп. 1-7 для применения в качестве терапевтически активных веществ для лечения болезни Альцгеймера, когнитивных нарушений, шизофрении, болей или нарушений сна.
12. Применение соединения по любому из пп. 1-7 для получения лекарственных средств для терапевтического и/или профилактического лечения болезни Альцгеймера, когнитивных нарушений, шизофрении, болей или нарушений сна.
13. Способ лечения или профилактики болезни Альцгеймера, когнитивных нарушений, шизофрении, болей или нарушений сна, который включает введение эффективного количества соединения по любому из пп. 1-7.
14. Применение соединения по любому из пп. 1-7 для лечения или профилактики болезни Альцгеймера, когнитивных нарушений, шизофрении, болей или нарушений сна.
RU2016132858A 2014-01-22 2015-01-19 Производные фторнафтила RU2016132858A (ru)

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EA201891854A1 (ru) 2016-02-16 2019-01-31 Вандербилт Юниверсити Положительные аллостерические модуляторы мускаринового ацетилхолинового рецептора m
JP6860551B2 (ja) 2016-03-11 2021-04-14 武田薬品工業株式会社 芳香環化合物
LT3507289T (lt) 2016-09-02 2020-10-12 Suven Life Sciences Limited Muskarininio m1 receptoriaus atžvilgiu teigiami alosteriniai moduliatoriai
WO2018063552A1 (en) 2016-09-30 2018-04-05 Vanderbilt University Positive allosteric modulators of the muscarinic acetylcholine receptor m1
EA035599B1 (ru) * 2017-04-13 2020-07-14 Сувен Лайф Сайенсиз Лимитед Позитивные аллостерические модуляторы мускариновых m1-рецепторов
US12298319B2 (en) 2017-05-19 2025-05-13 Takeda Pharmaceutical Company Limited Method for measuring alpha value of muscarinic M1 receptor positive allosteric modulators
MX2020004339A (es) * 2017-10-27 2020-08-03 Suven Life Sciences Ltd Moduladores alostericos positivos del receptor m1 muscarinico.
MA53917A (fr) 2018-10-17 2022-01-26 Suven Life Sciences Ltd Dérivés de pyrrolo-pyridazine en tant que modulateurs allostériques positifs du récepteur m1 muscarinique
WO2020086864A1 (en) 2018-10-24 2020-04-30 Vanderbilt University Positive allosteric modulators of the muscarinic acetylcholine receptor m1

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HRP20160574T1 (hr) * 2009-12-17 2016-06-17 Merck Sharp & Dohme Corp. Pozitivni alosterni modulatori m1 receptora na bazi hinolin amida
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