RU2002128733A - МОДУЛЯТОРЫ PPARγ - Google Patents

МОДУЛЯТОРЫ PPARγ

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Publication number
RU2002128733A
RU2002128733A RU2002128733/04A RU2002128733A RU2002128733A RU 2002128733 A RU2002128733 A RU 2002128733A RU 2002128733/04 A RU2002128733/04 A RU 2002128733/04A RU 2002128733 A RU2002128733 A RU 2002128733A RU 2002128733 A RU2002128733 A RU 2002128733A
Authority
RU
Russia
Prior art keywords
phenyl
nitrophenyl
carboxamide
chloro
group
Prior art date
Application number
RU2002128733/04A
Other languages
English (en)
Inventor
Йоси АМЕМИЯ (JP)
Йосия АМЕМИЯ
Кендзи ВАКАБАЯСИ (JP)
Кендзи ВАКАБАЯСИ
Сатико ТАКАИСИ (JP)
Сатико ТАКАИСИ
Тие ФУКУДА (JP)
Тие ФУКУДА
Original Assignee
Санкио Компани, Лимитед (Jp)
Санкио Компани, Лимитед
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 Санкио Компани, Лимитед (Jp), Санкио Компани, Лимитед filed Critical Санкио Компани, Лимитед (Jp)
Publication of RU2002128733A publication Critical patent/RU2002128733A/ru

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Claims (22)

1. Соединение следующей формулы (I) или его фармакологически приемлемая соль:
Figure 00000001
где А означает фенильную, нафтильную, аценафтенильную, пиридильную, хинолильную, изохинолильную, пиримидинильную, фурильную, бензофурильную, пиранильную, хроменильную, тиенильную, бензотиенильную, пирролильную, индолильную, изоиндолильную, имидазолильную, пиразолильную, пиридазинильную, пиразинильную, оксазолильную, изоксазолильную, бензоксазолильную, бензизоксазолильную, тиазолильную, изотиазолильную, бензотиазолильную, бензизотиазолильную или бифенильную группу (указанная группа А необязательно замещена одним, двумя или более заместителями, имеющими одинаковые или разные значения, которые выбирают из приведенной ниже группы заместителей α);
В означает арильную, циклоалкильную или гетероциклическую группу (указанная группа В необязательно замещена одним, двумя или более заместителями, имеющими одинаковые или разные значения, которые выбирают из приведенных ниже группы заместителей α и β);
Х означает связь, атом кислорода, атом серы, группу CH2, CO, NH, SO2NH, NHSO2, CONH, NHCO или OCH2;
n означает 0 или 1;
группа заместителей а включает С1-С20 алкильную группу, нитрогруппу, цианогруппу, карбоксильную группу, карбокси-С2-С7 алкильную группу, С2-С7 алкилоксикарбонильную группу, С3-С15 алкилоксикарбонилалкильную группу, аминогруппу (указанная аминогруппа необязательно замещена одной или двумя C1-C6 алкильными группами, имеющими одинаковые или разные значения, или C6-C3 алкенильной группой), гидроксильную группу (указанная гидроксильная группа необязательно замещена C1-Cg алкильной группой или C1-C6 галогеналкильной группой) и меркаптогруппу (указанная меркаптогруппа необязательно замещена C1-C6 алкильной группой);
группа заместителей β включает атом галогена, сульфонамидную группу, C1-C6 алкилсульфонамидную группу, амидиноаминосульфонильную группу или фенильную группу.
2. Соединение формулы (I) или его фармакологически приемлемая соль по п.1, где А означает тиазолильную группу.
3. Соединение, выбираемое из следующих соединений или их фармакологически премлемых солей:
N-[4-(трет-бутилоксикарбониламинофенил)]-(2-хлор-5-нитрофенил)карбоксамид;
N-[3-карбоэтокси-4,5,6,7-тетрагидробензо[Ь]тиофен-2-ил]-(2-хлор-5-нитрофенил)карбоксамид;
N-(3-метилбензимидазол-2-ил)-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(трет-бутоксикарбониламино)фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(6-ацетокси-2,5,7,8-тетраметил-4-оксохроман-2-илметокси)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(6-гидрокси-2,5,7,8-тетраметил-4-оксохроман-2-илметокси)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(амидиноаминосульфонил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(бутиламинокарбониламиносульфонил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-(5-фенил[1,3,4]тиадиазол-2-ил)-(2-хлор-5-нитрофенил)карбоксамид;
N-(4-ацетиламинофенил)-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(4-ацетиламинофенил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-(4-этансульфониламинофенил)-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(4-ацетоксифенил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-(4-метансульфониламинофенил)-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(пирролидинилсульфонил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(морфолин-4-илсульфонил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[3-(пирролидинилсульфонил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-(4-ацетилфенил)-(2-хлор-5-нитрофенил)карбоксамид;
N-(3-ацетилфенил)-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(2-трет-бутоксикарбониламиноэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
0,2 гидрат гидрохлорида N-[4-(2-аминоэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамида;
N-[4-[4-(морфолин-4-ил)фенил]аминосульфонил]фенил-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(4-ацетилпиперазин-1-ил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(4-бензоилпиперазин-1-ил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[[4-[4-(имидазол-1-ил)фенил]аминосульфонил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(4-трет-бутоксикарбониламинофенил)тиазол-2-ил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(пиридин-3-илкарбонил)пиперазин-1-ил]фенил]-2-(хлор-5-нитрофенил)карбоксамид;
N-[4-(2-гидроксиэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[[3-[4-(имидазол-1-ил)фенил]аминокарбонил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(3-трет-бутоксикарбониламинофенил)тиазол-2-ил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(метиламинотиокарбониламино)фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(2,2,2-трифтор-1-гидрокси-1-трифторметилэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(1-гидроксиэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[3-(1-гидроксиэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(фениламинокарбониламино)фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(аминокарбониламино)фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(этоксикарбониламинокарбониламино)фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-[(3-фторфенил)аминотиокарбониламино]фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-[(3-метоксифенил)аминокарбониламино]фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(бензиламинокарбониламино)фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-[(2,4-дифторфенил)аминокарбониламино]фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(бензоиламинотиокарбониламино)фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(этоксикарбониламинотиокарбониламино)фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(фениламинотиокарбониламино)фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(2-нитрофениламинокарбониламино)фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-[(пиридин-3-ил)аминотиокарбониламино]фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[(пиридин-3-ил)аминотиокарбониламино]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-[(пиридин-4-ил)аминотиокарбониламино]фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[(пиридин-4-ил)аминотиокарбониламино]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[(6-трет-бутоксикарбониламино)бензотиазол-2-ил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(4-метансульфониламинофенил)тиазол-2-ил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(4-ацетиламинофенил)тиазол-2-ил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[(4-аминокарбонил)пиперазин-1-ил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(2-ацетиламинотиазол-4-ил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[3-(2-ацетиламинотиазол-4-ил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(2-аминоэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(2-фениламинокарбониламиноэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(2-фениламинотиокарбониламиноэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(2-аминокарбониламиноэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(2-фенилкарбониламинотиокарбониламиноэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(2-этоксикарбониламинотиокарбониламиноэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[2-(пиридин-3-ил)аминотиокарбониламиноэтил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[3-(2-гидроксиэтил)фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-[4-(N,N-диэтансульфониламино)фенил]фенил]-(2-хлор-5-нитрофенил)карбоксамид;
N-[4-(3-ацетиламинофенил)тиазол-2-ил]-(2-хлор-5-нитрофенил)карбоксамид;
N-(6-ацетиламинобензотиазол-2-ил)-(2-хлор-5-нитрофенил)карбоксамид; и
N-(6-аминокарбониламинобензотиазол-2-ил)-(2-хлор-5-нитрофенил)карбоксамид.
4. Фармацевтическая композиция, включающая фармацевтически приемлемый разбавитель или носитель и соединение или его фармакологически приемлемую соль по любому из пп.1-3.
5. Соединение или его фармакологически приемлемая соль по любому из пп.1-3 для применения в качестве средства, ингибирующего дифференцировку адипоцитов в костном мозге.
6. Соединение или его фармакологически приемлемая соль по любому из пп.1-3 для применения в качестве средства, усиливающего или восстанавливающего функцию остеогенеза.
7. Соединение или его фармакологически приемлемая соль по любому из пп.1-3 для применения в качестве средства для лечения или профилактики остеопороза.
8. Соединение или его фармакологически приемлемая соль по любому из пп.1-3 для применения в качестве средства для лечения или профилактики старческого остеопороза, постклимактерического остеопороза или остеопороза, являющегося следствием прекращения приема лекарственных средств.
9. Соединение или его фармакологически приемлемая соль по любому из пп.1-3 для применения в качестве средства, обладающего моделирующей PPAR γ активностью.
10. Соединение или его фармакологически приемлемая соль по любому из пп.1-3 для применения в качестве средства, снижающего уровень сахара в крови.
11. Соединение или его фармакологически приемлемая соль по любому из пп.1-3 для применения в качестве средства для лечения или профилактики сахарного диабета.
12. Соединение или его фармакологически приемлемая соль по любому из пп.1-3 для применения в качестве средства для лечения или профилактики сахарного диабета типа I, сахарного диабета типа II, нарушения глюкозного обмена, диабетической невропатии или вызываемых диабетом осложнений.
13. Соединение или его фармакологически приемлемая соль по любому из пп.1-3 для применения в качестве средства для лечения или профилактики переломов, неполного остеогенеза, рахита, старческого артроза, ожирения, истощения, артериосклероза, нарушения липидного обмена, панкреатита, аутоиммунных заболеваний, гиперурикемии, лейкоза, функциональных нарушений родственных ретиноидам рецепторов, дисфункции печени, анемии, злокачественных опухолей, воспалений, базедовой болезни, заболеваний сердца, болезни Альцгеймера, нарушений питания, гипертензии или заболеваний почек.
14. Средство, ингибирующее дифференцировку адипоцитов в костном мозге, включающее соединение или его фармакологически приемлемую соль по любому из пп.1-3.
15. Средство, усиливающее или восстанавливающее функцию остеогенеза, включающее соединение или его фармакологически приемлемую соль по любому из пп.1-3.
16. Средство для лечения или профилактики остеопороза, включающее соединение или его фармакологически приемлемую соль по любому из пп.1-3.
17. Средство для лечения или профилактики старческого остеопороза, постклимактерического остеопороза или остеопороза, являющегося следствием прекращения приема лекарственных средств, включающее соединение или его фармакологически приемлемую соль по любому из пп.1-3.
18. Средство, обладающее модулирующей PPARγ активностью, включающее соединение или его фармакологически приемлемую соль по любому из пп.1-3.
19. Средство, снижающее уровень сахара в крови, включающее соединение или его фармакологически приемлемую соль по любому из пп.1-3.
20. Средство, предназначенное для лечения или профилактики сахарного диабета, включающее соединение или его фармакологически приемлемую соль по любому из пп.1-3.
21. Средство для лечения или профилактики сахарного диабета типа I, сахарного диабета типа II, нарушения глюкозного обмена, диабетической невропатии или вызываемых диабетом осложнений, включающее соединение или его фармацевтически приемлемую соль по любому из пп.1-3.
22. Средство для лечения или профилактики переломов, неполного остеогенеза, рахита, старческого артроза, ожирения, истощения, артериосклероза, нарушения липидного обмена, панкреатита, аутоиммунных заболеваний, гиперурикемии, лейкоза, функциональных нарушений родственных ретиноидам рецепторов, дисфункции печени, анемии, злокачественных опухолей, воспалений, базедовой болезни, заболеваний сердца, болезни Альцгеймера, нарушений питания, гипертензии или заболеваний почек, включающее соединение или его фармакологически приемлемую соль по любому из пп.1-3.
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