RU2443691C2 - Мочевинные активаторы глюкокиназы - Google Patents

Мочевинные активаторы глюкокиназы Download PDF

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RU2443691C2
RU2443691C2 RU2007147046/04A RU2007147046A RU2443691C2 RU 2443691 C2 RU2443691 C2 RU 2443691C2 RU 2007147046/04 A RU2007147046/04 A RU 2007147046/04A RU 2007147046 A RU2007147046 A RU 2007147046A RU 2443691 C2 RU2443691 C2 RU 2443691C2
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Еспер ЛАУ (DK)
Еспер ЛАУ
Энтони МЮРРЕЙ (DK)
Энтони Мюррей
Пер ВЕДСЁ (DK)
Пер ВЕДСЁ
Марит КРИСТИАНСЕН (DK)
Марит КРИСТИАНСЕН
Лоне ЙЕППЕСЕН (DK)
Лоне ЙЕППЕСЕН
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Abstract

Изобретение относится к новым соединениям формулы (1) или его фармацевтически приемлемым солям. Соединения активируют глюкокиназу и могут быть использованы для изготовления лекарства для лечения метаболических расстройств, для снижения уровня глюкозы в крови, для лечения гипергликемии, для лечения НТГ, для лечения синдрома X, для лечения нарушенной глюкозы натощак (НГН), для лечения диабета типа 2, для лечения диабета типа 1, для замедления прогрессирования нарушенной толерантности к глюкозе (НТГ) до диабета типа 2, для замедления прогрессирования инсулиннезависимого диабета типа 2 до инсулинозависимого диабета типа 2, для лечения дислипидемии, для лечения гиперлипидемии, для лечения гипертензии, для уменьшения приема пищи, для регуляции аппетита, для лечения ожирения, для регуляции пищевого поведения или для усиления секреции энтероинкретинов. В соединениях формулы (1) ! ! А представляет собой , R3 выбран из группы, состоящей из фенокси и бензилокси, каждый из которых возможно замещен одним или более чем одним заместителем, независимо выбранным из R12; R12 представляет собой F, Cl, Br, -CF3, -CN, метил, этил, изопропил, трет-бутил, метокси, метилтио, этокси, циклопропил-метокси, -NHC(O)СН3 или -S(O)2-СН3; R30 представляет собой метил, этил, пропил, изопропил, трет-бутил, циклопропил, циклобутил, циклопентил, циклогексил, фенил, метокси, этокси, пропокси, бутокси, трет-бутокси, бензилокси или циклопропил-метокси, каждый из которых возможно замещен одним или более чем одним заместителем, независимо выбранным из R12; R8 представляет собой метилтио, изопропилтио, этилтио или 2-метилпропилтио, каждый из которых замещен одним или более чем одни�

Description

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Claims (13)

1. Соединение формулы:
Figure 00000224

где R3 выбран из группы, состоящей из фенокси и бензилокси, каждый из которых возможно замещен одним или более чем одним заместителем, независимо выбранным из R12;
R12 представляет собой F, Cl, Br, -CF3, -CN, метил, этил, изопропил, трет-бутил, метокси, метилтио, этокси, циклопропил-метокси, -NHC(O)СН3 или -S(O)2-СН3;
R30 представляет собой метил, этил, пропил, изопропил, трет-бутил, циклопропил, циклобутил, циклопентил, циклогексил, фенил, метокси, этокси, пропокси, бутокси, трет-бутокси, бензилокси или циклопропил-метокси, каждый из которых возможно замещен одним или более чем одним заместителем, независимо выбранным из R12;
А представляет собой
Figure 00000225

R8 представляет собой метилтио, изопропилтио, этилтио или 2-метилпропилтио, каждый из которых замещен одним или более чем одним заместителем, независимо выбранным из R34;
R34 представляет собой карбокси;
или его фармацевтически приемлемая соль.
2. Соединение по п.1, где R12 представляет собой F, Cl, Br, метил или этил.
3. Соединение по п.1, где R30 представляет собой метил или этил.
4. Соединение по п.1, выбранное из группы, состоящей из: 2-{2-[3-[2-(2-хлор-бензилокси)-этил]-3-(4-транс-метил-циклогексил)-уреидо]-тиазол-5-илсульфанил}-2-метил-пропионовой кислоты и ее фармацевтически приемлемых солей.
5. Соединение по п.4, представляющее собой 2-{2-[3-[2-(2-хлор-бензилокси)-этил]-3-(4-транс-метил-циклогексил)-уреидо]-тиазол-5-илсульфанил}-2-метил-пропионовую кислоту.
6. Соединение по п.1, выбранное из группы, состоящей из 2-{2-[3-[2-(2-фтор-бензилокси)-этил]-3-(4-транс-метил-циклогексил)-уреидо]-тиазол-5-илсульфанил}-2-метил-пропионовой кислоты и ее фармацевтически приемлемых солей.
7. Соединение по п.6, представляющее собой 2-{2-[3-[2-(2-фтор-бензилокси)-этил]-3-(4-транс-метил-циклогексил)-уреидо]-тиазол-5-илсульфанил}-2-метил-пропионовую кислоту.
8. Фармацевтическая композиция, активирующая глюкокиназу, содержащая в качестве действующего начала по меньшей мере одно соединение по любому из пп.1-7 и фармацевтически приемлемый носитель.
9. Композиция по п.8, представляющая собой дозированную лекарственную форму, состоящую из от примерно 0,05 мг до примерно 1000 мг соединения по любому из пп.1-7.
10. Композиция по любому из пп.8 и 9, где эта дозированная лекарственная форма содержит от примерно 0,1 мг до примерно 500 мг соединения по любому из пп.1-7.
11. Композиция по любому из пп.8 и 9, где эта дозированная лекарственная форма содержит от примерно 0,5 мг до примерно 200 мг соединения по любому из пп.1-7.
12. Применение соединения по любому из пп.1-7 для изготовления лекарства для лечения метаболических расстройств, для снижения уровня глюкозы в крови, для лечения гипергликемии, для лечения НТГ, для лечения синдрома X, для лечения нарушенной глюкозы натощак (НГН), для лечения диабета типа 2, для лечения диабета типа 1, для замедления прогрессирования нарушенной толерантности к глюкозе (НТГ) до диабета типа 2, для замедления прогрессирования инсулиннезависимого диабета типа 2 до инсулинозависимого диабета типа 2, для лечения дислипидемии, для лечения гиперлипидемии, для лечения гипертензии, для уменьшения приема пищи, для регуляции аппетита, для лечения ожирения, для регуляции пищевого поведения или для усиления секреции энтероинкретинов.
13. Применение по п.12 для лечения показания, выбранного из группы, состоящей из гипергликемии, НТГ (нарушенной толерантности к глюкозе), синдрома устойчивости к инсулину, синдрома X, диабета типа 2, диабета типа 1, дислипидемии, гипертензии и ожирения.
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