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RU2019136694A - Фенил-2-гидрокси-ацетиламино-2-метил-фениловые соединения - Google Patents

Фенил-2-гидрокси-ацетиламино-2-метил-фениловые соединения Download PDF

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RU2019136694A
RU2019136694A RU2019136694A RU2019136694A RU2019136694A RU 2019136694 A RU2019136694 A RU 2019136694A RU 2019136694 A RU2019136694 A RU 2019136694A RU 2019136694 A RU2019136694 A RU 2019136694A RU 2019136694 A RU2019136694 A RU 2019136694A
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Prior art keywords
compound
pharmaceutically acceptable
methyl
acceptable salt
phenyl
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RU2019136694A
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RU2019136694A3 (ru
RU2804280C2 (ru
Inventor
Марта Мария СИФУЭНТЕС-ГАРСИЯ
Мария Кристина ГАРСИЯ-ПАРЕДЕС
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Эли Лилли Энд Компани
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • 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
    • A61K31/44Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4418Non condensed pyridines; Hydrogenated derivatives thereof having a carbocyclic group directly attached to the heterocyclic ring, e.g. cyproheptadine
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/4965Non-condensed pyrazines
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00Medicinal preparations containing organic active ingredients
    • A61K31/33Heterocyclic compounds
    • A61K31/395Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495Heterocyclic 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
    • A61K31/505Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A61K31/519Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61PSPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00Antineoplastic agents
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D213/00Heterocyclic 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
    • C07D213/02Heterocyclic 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
    • C07D213/78Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81Amides; Imides
    • C07D213/82Amides; Imides in position 3
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D239/00Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more 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, directly attached to ring carbon atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D241/00Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
    • C07D241/02Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
    • C07D241/10Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
    • C07D241/14Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having three 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
    • C07D241/24Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D241/26Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms
    • C07D241/28Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals with nitrogen atoms directly attached to ring carbon atoms in which said hetero-bound carbon atoms have double bonds to oxygen, sulfur or nitrogen atoms
    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D487/00Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04Ortho-condensed systems

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Medicinal Chemistry (AREA)
  • Public Health (AREA)
  • Epidemiology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (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)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Pyridine Compounds (AREA)

Claims (39)

1. Соединение формулы
Figure 00000001
где
R выбран из группы, состоящей из
Figure 00000002
и
Figure 00000003
;
X представляет собой CH или N;
R1 представляет собой водород или фтор; и
R2 представляет собой С13 алкил;
или его фармацевтически приемлемая соль.
2. Соединение по п.1 формулы
Figure 00000004
где
R выбран из группы, состоящей из
Figure 00000005
и
Figure 00000006
;
X представляет собой CH или N;
R1 представляет собой водород или фтор; и
R2 представляет собой С13 алкил;
или его фармацевтически приемлемая соль.
3. Соединение или соль по п. 1 или 2, где R представляет собой
Figure 00000007
.
4. Соединение или соль по п. 1 или 2, где
X представляет собой CH или N;
R1 представляет собой водород или фтор; и
R2 представляет собой метил или изопропил.
5. Соединение или соль по п. 1 или 2, где R представляет собой
Figure 00000008
.
6. Соединение по п.1 или 2, которое представляет собой 3-амино-6-[4-[[(2R)-2-(3,5-дифторфенил)-2-гидрокси-ацетил]амино]-2-метил-фенил]-N-метил-пиразин-2-карбоксамид, которое может быть представлено формулой
Figure 00000009
или его фармацевтически приемлемая соль.
7. Соединение по п. 1 или 2, которое представляет собой 2-амино-5-[4-[[(2R)-2-(3,5-дифторфенил)-2-гидрокси-ацетил]амино]-2-метил-фенил]-N-изопропил-пиридин-3-карбоксамид, которое может быть представлено формулой
Figure 00000010
или его фармацевтически приемлемая соль.
8. Соединение по п. 1 или 2, которое представляет собой (2R)-N-[4-(4-амино-7-метил-пирроло[2,3-d]пиримидин-5-ил)-3-метил-фенил]-2-(3-фторфенил)-2-гидрокси-ацетамид, которое может быть представлено формулой
Figure 00000011
или его фармацевтически приемлемая соль.
9. Фармацевтическая композиция, содержащая соединение или его фармацевтически приемлемую соль по любому из пп. 1-8 с одним или несколькими фармацевтически приемлемыми носителями, разбавителями или эксципиентами.
10. Способ лечения рака поджелудочной железы у пациента, включающий введение нуждающемуся в этом пациенту эффективного количества соединения по любому из пп.1-8 или его фармацевтически приемлемая соль.
11. Соединение или его фармацевтически приемлемая соль по любому из пп. 1-8 для применения в терапии.
12. Соединение или его фармацевтически приемлемая соль по любому из пп. 1-8 для применения при лечении рака поджелудочной железы.
RU2019136694A 2017-04-18 2018-04-11 Фенил-2-гидрокси-ацетиламино-2-метил-фениловые соединения RU2804280C2 (ru)

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Application Number Priority Date Filing Date Title
EP17382207.3 2017-04-18
EP17382207 2017-04-18
PCT/US2018/027005 WO2018194885A1 (en) 2017-04-18 2018-04-11 Phenyl-2-hydroxy-acetylamino-2-methyl-phenyl compounds

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RU2019136694A true RU2019136694A (ru) 2021-05-18
RU2019136694A3 RU2019136694A3 (ru) 2021-05-19
RU2804280C2 RU2804280C2 (ru) 2023-09-26

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