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RU2002117021A - Антагонист NPY Y5 - Google Patents

Антагонист NPY Y5

Info

Publication number
RU2002117021A
RU2002117021A RU2002117021/15A RU2002117021A RU2002117021A RU 2002117021 A RU2002117021 A RU 2002117021A RU 2002117021/15 A RU2002117021/15 A RU 2002117021/15A RU 2002117021 A RU2002117021 A RU 2002117021A RU 2002117021 A RU2002117021 A RU 2002117021A
Authority
RU
Russia
Prior art keywords
optionally substituted
alkyl
prodrug
solvate
compound
Prior art date
Application number
RU2002117021/15A
Other languages
English (en)
Other versions
RU2264810C2 (ru
Inventor
Ясуюки КАВАНИСИ (JP)
Ясуюки КАВАНИСИ
Хидеюки ТАКЕНАКА (JP)
Хидеюки ТАКЕНАКА
Кохдзи ХАНАСАКИ (JP)
Кохдзи ХАНАСАКИ
Тецуо ОКАДА (JP)
Тецуо Окада
Original Assignee
Сионоги Энд Ко., Лтд. (JP)
Сионоги Энд Ко., Лтд.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Сионоги Энд Ко., Лтд. (JP), Сионоги Энд Ко., Лтд. filed Critical Сионоги Энд Ко., Лтд. (JP)
Publication of RU2002117021A publication Critical patent/RU2002117021A/ru
Application granted granted Critical
Publication of RU2264810C2 publication Critical patent/RU2264810C2/ru

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Classifications

    • 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
    • A61K31/495—Heterocyclic 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
    • A61K31/4965—Non-condensed pyrazines
    • A61K31/497—Non-condensed pyrazines containing further heterocyclic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
    • C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
    • C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/00—Medicinal preparations containing organic active ingredients
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    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/18—Sulfonamides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/34—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
    • 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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    • A61K31/35—Heterocyclic 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
    • A61K31/351—Heterocyclic 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 not condensed with another ring
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    • A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
    • A61K31/4015—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil having oxo groups directly attached to the heterocyclic ring, e.g. piracetam, ethosuximide
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    • A61K31/403—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil condensed with carbocyclic rings, e.g. carbazole
    • A61K31/4035—Isoindoles, e.g. phthalimide
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    • 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
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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
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    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/42—Oxazoles
    • A—HUMAN NECESSITIES
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    • 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
    • A61K31/42—Oxazoles
    • A61K31/421—1,3-Oxazoles, e.g. pemoline, trimethadione
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    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4409—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 4, e.g. isoniazid, iproniazid
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    • A61K31/445—Non condensed piperidines, e.g. piperocaine
    • A61K31/451—Non condensed piperidines, e.g. piperocaine having a carbocyclic group directly attached to the heterocyclic ring, e.g. glutethimide, meperidine, loperamide, phencyclidine, piminodine
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    • C07C311/06—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by carboxyl groups
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Claims (20)

1. Фармацевтическая композиция для применения в качестве антагониста рецептора NPY Y5, содержащая соединение формулы (I)
Figure 00000001
где R1 представляет необязательно замещенный низший алкил, необязательно замещенный циклоалкил или необязательно замещенный арил;
R2 представляет водород или низший алкил, и R1 и R2, взятые вместе, могут образовывать низший алкилен;
n равно 1 или 2;
Х представляет необязательно замещенный низший алкилен, необязательно замещенный низший алкенилен, необязательно замещенный -СО-(низший алкилен), необязательно замещенный -СО-(низший алкенилен) или
Figure 00000002
где R3, R4, R5 и R6, каждый независимо, представляют водород или низший алкил,
Figure 00000003
представляет собой необязательно замещенный циклоалкилен, необязательно замещенный циклоалкенилен, необязательно замещенный бициклоалкилен, необязательно замещенный арилен или необязательно замещенный гетероциклдиил, и р и q, каждый независимо, равен 0 или 1,
-NR2-X- может представлять
Figure 00000004
где
Figure 00000005
представляет пиперидиндиил, пиперазиндиил, пиридиндиил, пиразиндиил, пирролидиндиил или пирролдиил, и U представляет простую связь, низший алкилен или низший алкенилен;
Y представляет OCONR7, CONR7, CSNR7, NR7CO или NR7CS;
R7 представляет водород или низший алкил;
Z представляет необязательно замещенный низший алкил, необязательно замещенный низший алкенил, необязательно замещенный амино, необязательно замещенный низший алкокси, необязательно замещенный карбоциклил или необязательно замещенный гетероциклил,
его пролекарство, фармацевтически приемлемая соль или сольват.
2. Фармацевтическая композиция для применения в качестве антагониста рецептора NPY Y5 по п.1, где R2 представляет водород или низший алкил и Z представляет необязательно замещенный низший алкил, необязательно замещенный низший алкенил, необязательно замещенный низший алкокси, необязательно замещенный карбоциклил, необязательно замещенный гетероциклил или необязательно замещенный амино, при условии, что R1 представляет необязательно замещенный (С3-С10)алкил, когда Z представляет необязательно замещенный амино.
3. Фармацевтическая композиция для применения в качестве антагониста рецептора NPY Y5 по п.1, где R1 представляет необязательно замещенный низший алкил или необязательно замещенный циклоалкил, Х представляет необязательно замещенный низший алкилен, необязательно замещенный низший алкенилен или
Figure 00000006
где
Figure 00000007
имеет значения, установленные в п.1, и
Z представляет необязательно замещенный низший алкил, необязательно замещенный карбоциклил или необязательно замещенный гетероциклил.
4. Фармацевтическая композиция для применения в качестве антагониста рецептора NPY Y5 по любому из пп.1-3, где R1 представляет необязательно замещенный (С3-С10)алкил.
5. Фармацевтическая композиция для применения в качестве антагониста рецептора NPY Y5 по любому из пп.1-4, являющаяся средством против ожирения.
6. Фармацевтическая композиция для применения в качестве антагониста рецептора NPY Y5 по любому из пп.1-4, являющаяся средством, снижающим аппетит.
7. Способ лечения и/или предупреждения ожирения, включающий введение эффективной дозы антагониста рецептора NPY Y5 по любому из пп.1-4.
8. Способ подавления потребления пищи, включающий введение эффективной дозы антагониста рецептора NPY Y5 по любому из пп.1-4.
9. Применение антагониста рецептора NPY Y5 по любому из пп.1-4 для изготовления лечебного средства для лечения и/или предупреждения ожирения.
10. Применение антагониста рецептора NPY Y5 по любому из пп.1-4 для изготовления лечебного средства для подавления потребления пищи.
11. Соединение формулы (I)
Figure 00000008
где Х представляет (С2-С6)алкилен или (С3-С6)алкенилен, R1 представляет необязательно замещенный (С3-С10)алкил или необязательно замещенный (С5-С6)циклоалкил и другие символы имеют значения, указанные в п.1, при условии, что Z не является низшим алкилфениламино, гидрокси(низший)алкилфениламино и ацилфениламино, когда Y представляет NR7CO,
его пролекарство, фармацевтически приемлемая соль или сольват.
12. Соединение по п.11, где Z представляет необязательно замещенный низший алкил или необязательно замещенный фенил, его пролекарство, фармацевтически приемлемая соль или сольват.
13. Соединение формулы (I)
Figure 00000009
где Х представляет
Figure 00000010
Figure 00000011
представляет необязательно замещенный циклоалкилен, необязательно замещенный циклоалкенилен, необязательно замещенный бициклоалкилен или необязательно замещенный пиперидинилен, R1 представляет необязательно замещенный (С3-С10)алкил или необязательно замещенный (С5-С6)циклоалкил и другие символы имеют значения, указанные в п.1,
его пролекарство, фармацевтически приемлемая соль или сольват.
14. Соединение по п.13, где
Figure 00000012
представляет необязательно замещенный циклогексилен или необязательно замещенный пиперидинилен, и р и q одновременно равны 0, его пролекарство, фармацевтически приемлемая соль или сольват.
15. Соединение по п.13 или 14, где Y представляет CONH, его пролекарство, фармацевтически приемлемая соль или сольват.
16. Соединение по пп.13-15, где Z представляет необязательно замещенный низший алкил, необязательно замещенный фенил, необязательно замещенный пиридил или необязательно замещенный бензопиранил, его пролекарство, фармацевтически приемлемая соль или сольват.
17. Соединение формулы (I)
Figure 00000013
где X представляет
Figure 00000014
R1 представляет необязательно замещенный (С3-С10)алкил или необязательно замещенный (С5-С6)циклоалкил, Z представляет п-(низший)алкилфенил, и другие символы имеют значения, указанные в п.1, при условии, что Z не является п-н-бутилфенилом, когда R1 представляет изопропил, его пролекарство, фармацевтически приемлемая соль или сольват.
18. Соединение формулы (I)
Figure 00000015
где Х представляет
Figure 00000016
Figure 00000017
представляет гетероарилен, R1 представляет необязательно замещенный (C3-C10)алкил или необязательно замещенный (C5-C6)циклоалкил, и другие символы имеют значения, указанные в п.1, его пролекарство, фармацевтически приемлемая соль или сольват.
19. Соединение по п.18, где
Figure 00000018
представляет тиофендиил или фурандиил, его пролекарство, фармацевтически приемлемая соль или сольват.
20. Фармацевтическая композиция, содержащая соединение по любому из пп.11-19, его пролекарство, фармацевтически приемлемую соль или сольват.
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