EA202192275A1 - Замещенные амидные соединения, полезные в качестве модуляторов фарнезоидного x-рецептора - Google Patents

Замещенные амидные соединения, полезные в качестве модуляторов фарнезоидного x-рецептора

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Publication number
EA202192275A1
EA202192275A1 EA202192275A EA202192275A EA202192275A1 EA 202192275 A1 EA202192275 A1 EA 202192275A1 EA 202192275 A EA202192275 A EA 202192275A EA 202192275 A EA202192275 A EA 202192275A EA 202192275 A1 EA202192275 A1 EA 202192275A1
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EA
Eurasian Patent Office
Prior art keywords
compounds
pharnesoid
compounds useful
receptor modulators
amide compounds
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EA202192275A
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English (en)
Inventor
Дин А. Уокер
Сушил Джетхананд Нара
Сринива Черуку
Кандхасами Саркунам
Фироз Али Джайпури
Соодамани Тхангавел
Ришикеш Нарайян
Сринивас Джоги
Паван Кальян Катхи
Original Assignee
Бристол-Маерс Сквибб Компани
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Application filed by Бристол-Маерс Сквибб Компани filed Critical Бристол-Маерс Сквибб Компани
Publication of EA202192275A1 publication Critical patent/EA202192275A1/ru

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    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic 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
    • C07D213/02—Heterocyclic 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
    • C07D213/04—Heterocyclic 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
    • C07D213/24—Heterocyclic 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 substituted hydrocarbon radicals attached to ring carbon atoms
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    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • 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
    • A61K31/41—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
    • A61K31/4245—Oxadiazoles
    • 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
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • 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
    • A61K31/66—Phosphorus compounds
    • A61K31/675—Phosphorus compounds having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
    • 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
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
    • C07C237/24—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a ring other than a six-membered aromatic ring of the carbon skeleton
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    • C07D213/02—Heterocyclic 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
    • C07D213/04—Heterocyclic 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
    • C07D213/24—Heterocyclic 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 substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/26—Radicals substituted by halogen atoms or nitro radicals
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    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
    • C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
    • C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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    • C07—ORGANIC CHEMISTRY
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    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
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    • 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
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    • C07D403/02—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 two hetero rings
    • C07D403/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D407/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings
    • C07D407/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having oxygen atoms as the only ring hetero atoms, not provided for by group C07D405/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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  • Gastroenterology & Hepatology (AREA)
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  • Molecular Biology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pyridine Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)

Abstract

Раскрыты соединения формулы (I)или их стереоизомер, таутомер, или фармацевтически приемлемая соль, или сольват, где Q представляет собой (i) галоген, циано, гидроксил, -NRxRx, -C(O)OH, -C(O)NH2, C1-6алкил, замещенный от 0 до 6 R1a, или -P(O)R1cR1c; или (ii) -L-R1; и A, X1, X2, X3, X4, Z1, Z2, R1, R1a, R1c, R2, R3a, R3b, Rx, L, a, b и d определены в данном документе. Также раскрыты способы применения этих соединений для модуляции активности фарнезоидного X-рецептора (FXR); фармацевтические композиции, содержащие эти соединения; и способы лечения заболевания, расстройства или состояния, связанного с нарушением регуляции FXR, такого как патологический фиброз, отторжение трансплантата, рак, остеопороз и воспалительные расстройства, путем применения этих соединений и фармацевтических композиций.
EA202192275A 2019-02-15 2020-02-14 Замещенные амидные соединения, полезные в качестве модуляторов фарнезоидного x-рецептора EA202192275A1 (ru)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201962806060P 2019-02-15 2019-02-15
PCT/US2020/018211 WO2020168149A1 (en) 2019-02-15 2020-02-14 Substituted amide compounds useful as farnesoid x receptor modulators

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EA202192275A1 true EA202192275A1 (ru) 2021-11-03

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US (1) US20220081430A1 (ru)
EP (1) EP3924333A1 (ru)
JP (1) JP2022519771A (ru)
KR (1) KR20210129684A (ru)
CN (1) CN113727973A (ru)
AU (1) AU2020223150A1 (ru)
BR (1) BR112021015688A2 (ru)
CA (1) CA3129851A1 (ru)
EA (1) EA202192275A1 (ru)
IL (1) IL285510A (ru)
MX (1) MX2021009424A (ru)
SG (1) SG11202108794RA (ru)
WO (1) WO2020168149A1 (ru)

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AR118050A1 (es) 2019-02-15 2021-09-15 Bristol Myers Squibb Co Compuestos bicíclicos sustituidos como moduladores del receptor farnesoide x
EP4294784A1 (en) * 2021-02-22 2023-12-27 The Trustees of Princeton University 2-substituted bicyclo[1.1.1]pentanes
WO2024030121A1 (en) * 2022-08-02 2024-02-08 The Scripps Research Institute Small-molecule activators of mycobacterium tuberculosis adenylyl cyclase

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JP4383177B2 (ja) 2002-03-01 2009-12-16 スミスクライン ビーチャム コーポレーション ｈＰＰＡＲ活性化剤
PL2402002T3 (pl) 2005-04-08 2018-11-30 Ptc Therapeutics, Inc. Kompozycje zawierające kwas 1,2,4-oksadiazolobenzoesowy i ich zastosowania do leczenia chorób związanych z przedwczesnym kodonem stop
WO2008011130A2 (en) 2006-07-21 2008-01-24 Takeda Pharmaceutical Company Limited Amide compounds
EP2917203B1 (en) 2012-11-02 2019-04-03 Dana-Farber Cancer Institute, Inc. Method for identifying myc inhibitors
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EP3019196B1 (en) 2013-07-09 2018-06-06 Bristol-Myers Squibb Company Combinations of hepatitis c virus inhibitors
WO2016039734A1 (en) 2014-09-10 2016-03-17 Halliburton Energy Services, Inc. Perforating gun with integrated retaining system
WO2018170166A1 (en) * 2017-03-15 2018-09-20 Metacrine, Inc. Farnesoid x receptor agonists and uses thereof
SG11201908330PA (en) * 2017-03-15 2019-10-30 Metacrine Inc Farnesoid x receptor agonists and uses thereof

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JP2022519771A (ja) 2022-03-24
SG11202108794RA (en) 2021-09-29
CN113727973A (zh) 2021-11-30
IL285510A (en) 2021-09-30
EP3924333A1 (en) 2021-12-22
CA3129851A1 (en) 2020-08-20
WO2020168149A1 (en) 2020-08-20
US20220081430A1 (en) 2022-03-17
AU2020223150A1 (en) 2021-10-07
MX2021009424A (es) 2021-09-10
KR20210129684A (ko) 2021-10-28

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