KR20050075386A - 유효한 항고혈당증 및 항고지질증 활성을 갖는 ppar광범위 어고니스트로서 치환 아릴알카노 산 유도체 - Google Patents
유효한 항고혈당증 및 항고지질증 활성을 갖는 ppar광범위 어고니스트로서 치환 아릴알카노 산 유도체 Download PDFInfo
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- KR20050075386A KR20050075386A KR1020057008310A KR20057008310A KR20050075386A KR 20050075386 A KR20050075386 A KR 20050075386A KR 1020057008310 A KR1020057008310 A KR 1020057008310A KR 20057008310 A KR20057008310 A KR 20057008310A KR 20050075386 A KR20050075386 A KR 20050075386A
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- ring
- alkyl
- aryl
- amino
- heteroaryl
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Abstract
Description
동물군 | 복용량(mg/kg) | 트리글리세라이드(mg/dl) | 콜레스테롤(mg/dl) |
정상 | - | 149±39.8* | 73.1±7.8** |
대조군 | - | 233.9±101.6 | 109.4±26.7 |
CS038 | 4 | 150.3±52.1* | 98.4±29.4 |
CS038 | 30 | 143.2±61.8* | 86.6±37.7 |
Ros | 4 | 273.3±87.4 | 112.7±25.5 |
동물군 | 복용량(mg/kg) | 체중(g) | 복부지방무게(g) | |||
0일 | 6일 | 9일 | 15일 | |||
Con | - | 576.5±138.0 | 569.4±142.1 | 568.5±145.3 | 562.7±136.5 | 60.4±21.0 |
CS038 | 4 | 591.5±130.0 | 580.8±130.2 | 575.2±130.6 | 569.4±122.9 | 55.8±16.8 |
CS038 | 30 | 580.5±134.9 | 586.1±143.2 | 586.5±144.2 | 578.3±176.8 | 56.6±21.1 |
Ros | 4 | 594.9±169.3 | 604.5±181.4 | 601.6±183.9 | 596.4±176.8 | 63.1±31.4 |
Claims (28)
- 다음 구조식 I의 화합물(I)여기서, X 및 N을 포함하는 고리에 융합된 고리 A 및 고리 B는 각각 독립적으로 5-6 원소의 환식 고리로, 임의적으로 산소, 황 또는 질소 원자에서 선택된 하나 또는 그 이상의 헤테로원자를 포함할 수 있고, 그리고 임의적으로 하나 또는 그 이상의 할로겐, 하이드록시, 니트로, 시아노, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노로 치환될 수 있고; 고리 A 및 고리 B는 포화되거나 또는 하나 또는 그 이상의 이중 결합을 포함하거나 또는 방향족일 수 있고;X는 원자가 결합, CH2CH2, CH=CH, O, S, 또는 NR6 이고 여기서 R6은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴임;R1 은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, OH, 할로겐, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노이고;R2는 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴이고;R3은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴이고;R4 및 R5는 독립적으로 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, OH, 할로겐, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노이고; R4 및 R5는 하나 또는 그 이상의 할로겐, 하이드록시, 니트로, 시아노, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알실, 하이드록시알킬, 티오알킬, 헤테로사이크릴, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노로 임의적으로 로 치환된 5 또는 6원소의 고리를 형성할 수 있고;Alkl은 Cl-6알킬렌이고;Alk2는 Cl-2알킬렌이고;Arl은 아릴렌, 헤테로 아릴렌, 또는 하나 또는 그 이상의 할로겐, Cl-6알킬, 아미노, 하이드록시, Cl-6알콕실 또는 아릴로 임의적으로 치환된 이가의 헤테로사이클 기이고,Ar2는 비치환, 하나 또는 그 이상의 할로겐, Cl-6알킬, 아미노, 하이드록시, C1-6알콕실 또는 아릴로 치환된 아릴 기; 헤테로 아릴, 또는 하나 또는 그 이상의 할로겐, C1-6알킬, 아미노, 하이드록시, Cl-6알콕실 또는 아릴로 임의적으로 치환된 헤테로사이클 기이다.
- 제 1항에 있어서,여기서, 고리 A는 6원소의 방향족 고리이고;고리 B는 6원소의 방향족 고리이고;X는 원자가 결합, CH2CH2, CH=CH, O 또는 S이고;Rl은 H 또는 알킬이고;R2는 H 또는 알킬이고;R3은 H 또는 알킬이고;R4 및 R5는 독립적으로 H 또는 알킬이고;Alkl은 C2-3알킬렌이고;Alk2는 Cl-2알킬렌이고;Arl은 아릴렌 기이고;Ar2는 치환된 아릴 기인 화합물.
- 제 1항에 있어서,여기서, 고리 A는 6 원소의 방향족 고리이고;고리 B는 6 원소의 방향족 고리이고;X는 원자가 결합, CH2CH2, CH=CH, O 또는 S이고;Rl는 H 또는 알킬이고;R2는 H 또는 알킬이고;R3는 H 또는 알킬이고;R4 및 R5는 6 원소의 방향족 고리를 형성하고;Alk1은 C2-3알킬렌이고;Alk2는 C1-2알킬렌이고 ;Arl는 6 원소의 방향족 고리이고;Ar2는 치환된 아릴 기인 화합물.
- 제 1항에 있어서,여기서, 고리 A는 벤젠 고리이고;고리 B는 벤젠 고리이고;X는 원자가 결합, CH2CH2, CH=CH, O 또는 S이고;Rl는 H이고;R2는 H이고;R3는 H이고;R4는 메틸이고; R5는 H이고;Alk1는 CH2CH2이고;Alk2는 CH2이고;Arl는 벤젠 고리이고;Ar2는 비치환 또는, 하나 또는 그 이상의 불소로 치환된 벤젠 고리인 화합물.
- 제 1항에 있어서,여기서, 고리 A는 벤젠 고리이고;고리 B는 벤젠 고리이고;X는 원자가 결합, CH2CH2, CH=CH, O 또는 S이고;R1은 H이고;R2는 H이고;R3는 H이고;R4 및 R5는 벤젠 고리를 형성하고;Alkl는 CH2CH2이고;Alk2는 CH2이고;Arl는 벤젠 고리이고;Ar2는 비치환 또는, 하나 또는 그 이상의 불소로 치환된 벤젠 고리인 화합물.
- 제 1항에 있어서,여기서, 고리 A는 벤젠 고리이고;고리 B는 벤젠 고리이고;X는 원자가 결합, CH2CH2, CH=CH, O 또는 S이고;R1는 H이고;R2는 H이고;R3는 H이고;R4는 메틸이고;R5는 H이고;Alkl는 CH2CH2이고;Alk2는 CH2이고;Arl는 벤젠 고리이고;Ar2는 비치환 또는, 하나 또는 그 이상의 할로겐으로 치환된 피리딘 고리인 화합물.
- 제 1항에 있어서,여기서, 고리 A는 벤젠 고리이고;고리 B는 벤젠 고리이고;X는 원자가 결합, CH2CH2, CH=CH, O 또는 S이고;R1는 H이고;R2는 H이고;R3는 H이고;R4 및 R5는 벤젠 고리를 형성하고;Alkl는 CH2CH2이고;Alk2는 CH2이고;Arl는 벤젠 고리이고;Ar2는 비치환 또는, 하나 또는 그 이상의 불소로 치환된 피리딘 고리인 화합물.
- a) 화합물 1과 D-디케톤 2 사이에 축합반응을 시작하여 비닐형 아미드 유사화합물 3을 얻는 단계;b) 3의 O-알킬화반응을 수행하여 화합물 4를 얻는 단계;c) 4의 N-알킬화반응을 수행하여 치환된 아릴알카노 산 유도체 6을 얻는 단계;를 포함하는다음 구조식 I의 화합물;(I)여기서, X 및 N을 포함하는 고리에 융합된 고리 A 및 고리 B는 각각 독립적으로 5-6 원소의 환식 고리로, 임의적으로 산소, 황 또는 질소 원자에서 선택된 하나 또는 그 이상의 헤테로원자를 포함할 수 있고, 그리고 임의적으로 하나 또는 그 이상의 할로겐, 하이드록시, 니트로, 시아노, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노로 치환될 수 있고; 고리 A 및 고리 B는 포화되거나 또는 하나 또는 그 이상의 이중 결합을 포함하거나 또는 방향족일 수 있고;X는 원자가 결합, CH2CH2, CH=CH, O, S, 또는 NR6 이고 여기서 R6은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴임;R1 은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, OH, 할로겐, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노이고;R2는 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴이고;R3은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴이고;R4 및 R5는 독립적으로 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, OH, 할로겐, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노이고; R4 및 R5는 하나 또는 그 이상의 할로겐, 하이드록시, 니트로, 시아노, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알실, 하이드록시알킬, 티오알킬, 헤테로사이크릴, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노로 임의적으로 로 치환된 5 또는 6원소의 고리를 형성할 수 있고;Alkl은 Cl-6알킬렌이고;Alk2는 Cl-2알킬렌이고;Arl은 아릴렌, 헤테로 아릴렌, 또는 하나 또는 그 이상의 할로겐, Cl-6알킬, 아미노, 하이드록시, Cl-6알콕실 또는 아릴로 임의적으로 치환된 이가의 헤테로사이클 기이고,Ar2는 비치환, 하나 또는 그 이상의 할로겐, Cl-6알킬, 아미노, 하이드록시, C1-6알콕실 또는 아릴로 치환된 아릴 기; 헤테로 아릴렌, 또는 비치환되거나 하나 또는 그 이상의 할로겐, C1-6알킬, 아미노, 하이드록시, Cl-6알콕실 또는 아릴로 임의적으로 치환된 이가의 헤테로사이클 기임,이들의 입체 이성체(stereoisomer), 거울상 이성질체(enantiomer), 경상이성체(diastereomer), 수화물 또는 약학적으로 허용될 수 있는 염의 제조 방법.
- 제 8항에 있어서, (a) 축합반응은 에탄올 내에서 환류온도에서 수행되고; (b) O-알킬화반응은 3을 KOH 및 디브로모알칸으로 에탄올에서 처리함에 의해 이루어지고; (c) N-알킬화반응은 테트라부틸 암모니움 브로마이드의 존재하에 화합물 4를 NaOH 및 화합물 5로 처리함에 의해 달성되는 방법.
- 제 1항에 있어서, 상기 화합물는 RXR/PPAR알파, RXR/PPAR감마, 및 RXR/PPAR델타 헤테로다이머를 활성화하는 PPAR 광범위 어고니스트인 화합물.
- 제 10항에 있어서, 상기 화합물는 RXR/PPAR알파, RXR/PPAR감마, 및 RXR/PPAR델타 헤테로다이머를 다른 정도로 활성화하는 부분적 PPAR 광범위 어고니스트인 화합물.
- 적어도 하나의 약학적으로 허용될 수 있는 담체 또는 희석제를 갖는 청구항 1에 따른 화합물 또는 이의 약학적으로 허용될 수 있는 염을 유효량으로 포함하는 핵 수용체 활성화용 약학적 조성물.
- 제 11항에 있어서, 핵 수용체는 레티노이드 X 리셉터(Retinoid X Receptors; RXR) 및 퍼옥시좀 증식자-활성화 리셉터(Peroxisome Proliferator-Activated Receptors; PPAR)를 포함하는 약학적 조성물.
- 약 0.05 내지 약 200 mg의 화합물을 포함하는 단위 복용량 형식의 청구항 12의 약학적 조성물.
- 약 0.1 내지 약 100 mg의 화합물을 포함하는 단위 복용량 형식의 청구항 14의 약학적 조성물.
- 경구, 비강, 피하, 폐 또는 비경구 경로에 의한 투여에 적절한 청구항 12의 약학적 조성물.
- 다음 구조식 I의 화합물을 그 요구되는 대상에 유효성분으로 투여하는 것을 포함하는 적어도 하나의 핵 수용체에 매개된 증상을 치료 또는 예방하는 방법.(I)여기서, X 및 N을 포함하는 고리에 융합된 고리 A 및 고리 B는 각각 독립적으로 5-6 원소의 환식 고리로, 임의적으로 산소, 황 또는 질소 원자에서 선택된 하나 또는 그 이상의 헤테로원자를 포함할 수 있고, 그리고 임의적으로 하나 또는 그 이상의 할로겐, 하이드록시, 니트로, 시아노, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노로 치환될 수 있고; 고리 A 및 고리 B는 포화되거나 또는 하나 또는 그 이상의 이중 결합을 포함하거나 또는 방향족일 수 있고;X는 원자가 결합, CH2CH2, CH=CH, O, S, 또는 NR6 이고 여기서 R6은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴임;R1 은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, OH, 할로겐, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노이고;R2는 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴이고;R3은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴이고;R4 및 R5는 독립적으로 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, OH, 할로겐, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노이고; R4 및 R5는 하나 또는 그 이상의 할로겐, 하이드록시, 니트로, 시아노, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알실, 하이드록시알킬, 티오알킬, 헤테로사이크릴, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노로 임의적으로 로 치환된 5 또는 6원소의 고리를 형성할 수 있고;Alkl은 Cl-6알킬렌이고;Alk2는 Cl-2알킬렌이고;Arl은 아릴렌, 헤테로 아릴렌, 또는 하나 또는 그 이상의 할로겐, Cl-6알킬, 아미노, 하이드록시, Cl-6알콕실 또는 아릴로 임의적으로 치환된 이가의 헤테로사이클 기이고,Ar2는 비치환, 하나 또는 그 이상의 할로겐, Cl-6알킬, 아미노, 하이드록시, C1-6알콕실 또는 아릴로 치환된 아릴 기; 헤테로 아릴, 또는 하나 또는 그 이상의 할로겐, C1-6알킬, 아미노, 하이드록시, Cl-6알콕실 또는 아릴로 임의적으로 치환된 헤테로사이클 기이다.
- 제 17항에 있어서, 핵 수용체는 레티노이드 X 리셉터(Retinoid X Receptors; RXR) 및 퍼옥시좀 증식자-활성화 리셉터(Peroxisome Proliferator-Activated Receptors; PPAR)를 포함하는 방법.
- 다음 구조식 I의 화합물을 그 요구되는 대상에 유효성분으로 투여하는 것을 포함하는 적어도 하나의 핵 수용체의 감소된 활성에 매개된 증상을 치료 또는 예방하는 방법.(I)여기서, X 및 N을 포함하는 고리에 융합된 고리 A 및 고리 B는 각각 독립적으로 5-6 원소의 환식 고리로, 임의적으로 산소, 황 또는 질소 원자에서 선택된 하나 또는 그 이상의 헤테로원자를 포함할 수 있고, 그리고 임의적으로 하나 또는 그 이상의 할로겐, 하이드록시, 니트로, 시아노, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노로 치환될 수 있고; 고리 A 및 고리 B는 포화되거나 또는 하나 또는 그 이상의 이중 결합을 포함하거나 또는 방향족일 수 있고;X는 원자가 결합, CH2CH2, CH=CH, O, S, 또는 NR6 이고 여기서 R6은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴임;R1 은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, OH, 할로겐, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노이고;R2는 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴이고;R3은 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 헤테로사이크릴, 아릴, 또는 헤테로아릴이고;R4 및 R5는 독립적으로 H, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알킬, 하이드록시알킬, 티오알킬, 헤테로사이크릴, OH, 할로겐, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노이고; R4 및 R5는 하나 또는 그 이상의 할로겐, 하이드록시, 니트로, 시아노, 알킬, 알케닐, 알케니닐, 아르알킬, 헤테로아릴알킬, 아미노알킬, 알콕시알킬, 아릴옥시알킬, 아르알콕시알실, 하이드록시알킬, 티오알킬, 헤테로사이크릴, 알콕시, 아릴, 아릴옥시, 아르알콕시, 헤테로아릴, 헤테로아릴옥시, 헤테로아르알콕시, 아실, 아실옥시, 아미노, 알킬아미노, 아릴아미노, 또는 아르알킬아미노로 임의적으로 로 치환된 5 또는 6원소의 고리를 형성할 수 있고;Alkl은 Cl-6알킬렌이고;Alk2는 Cl-2알킬렌이고;Arl은 아릴렌, 헤테로 아릴렌, 또는 하나 또는 그 이상의 할로겐, Cl-6알킬, 아미노, 하이드록시, Cl-6알콕실 또는 아릴로 임의적으로 치환된 이가의 헤테로사이클 기이고,Ar2는 비치환, 하나 또는 그 이상의 할로겐, Cl-6알킬, 아미노, 하이드록시, C1-6알콕실 또는 아릴로 치환된 아릴 기; 헤테로 아릴, 또는 하나 또는 그 이상의 할로겐, C1-6알킬, 아미노, 하이드록시, Cl-6알콕실 또는 아릴로 임의적으로 치환된 헤테로사이클 기이다.
- 제 19항에 있어서, 상기 증상은 타잎 1 당뇨병, 타잎 2 당뇨병, 저지질증, 심드롬 X, 심혈관질환, 아테롬성 동맥경화증, 고콜레스테롤증 및 비만으로 구성된 군에서 선택된 방법.
- 제 20항에 있어서, 화합물의 유효량은 일일당 약 0.05 내지 약 200mg/kg의 범위인 방법.
- 제 21항에 있어서, 화합물의 유효량은 일일당 약 0.1 내지 약 100mg/kg의 범위인 방법.
- 제 22항에 있어서, 화합물의 유효량은 일일당 약 0.1 내지 약 50mg/kg의 범위인 방법.
- 제 19항에 있어서, 동일한 복용형태로 경구로, 별도의 경구 복용형태로 또는 주사로 복용될 수 있는 저지질증제, 지질저하제제, 지질조절제, 항당뇨제제, 항비만제제, 항고혈압제제, 및 혈소판 응집저해제로 구성된 군에서 선택된 적어도 하나의 제제와 조합한 유효량의 화합물을 그 요구되는 대상에 투여하는 것을 포함하는 증상을 치료 또는 예방하는 방법.
- 제 24항에 있어서, 저지질증제 또는 지질저하제제 또는 지질조절제는 적어도 하나의 MTP 저해제(inhibitor), HMG CoA 리덕타제 저해제(reductase inhibitor), 스쿠알렌 합성제 저해제(squalene synthetase inhibitor), 피브린산 유도체(fibric acid derivative), ACAT 저해제, 리폭시게나제(lipoxygenase) 저해제, 콜레스테롤 흡수 저해제, 회장(ileal) Na+/담즙산 코트랜스포터(cotransporter) 저해제, LDL 리셉터 활성의 엎레귤레이터(upregulator), 담즙산 스퀘스트런트(bile acid sequestrant), 및 니코틴산(nicotinic acid) 또는 이들의 유도체로 구성된 군에서 선택된 것인 증상을 치료 또는 예방하는 방법.
- 제 24항에 있어서, 적어도 하나의 항당뇨제제는 인슐린 분비촉진제(an insulin secretagogue), 인슐린 민감제(insulin sensitizer), 비구아나이드(biguanide), 술포닐 우레아(sulfonyl urea), 글루코시다제 저해제, PPAR y 부분적 어고니스트 또는 안타고니스트, 티아조리딘디온(thiazolidinedione), P2 저해제, 디펩티딜 펩티다제(dipeptidyl peptidase) IV (DP4) 저해제, SGLT2 저해제, 메그리티나이드(meglitinide), 인슐린 및 글루카곤-형 펩티드-1 (GLP-1)로 구성된 군에서 선택된 것인 증상을 치료 또는 예방하는 방법.
- 제 24항에 있어서, 적어도 하나의 제제는 항비만제, 베타 3 아드레날린 어고니스트, 리파제 저해제, 세로토닌(및 도파민) 리업테이크 저해제, P2 저해제, 티로이드 리셉터 어고니스트, 및 식용감퇴제로 구성된 군에서 선택된 것인 증상을 치료 또는 예방하는 방법.
- 제 24항에 있어서, 적어도 하나의 항고혈압제제는 ACE 저해제, 안지오텐신 II 리셉터 안타고니스트, NEP/ACE 저해제, 칼슘 채널 블록커(calcium channel blocker), β-아드레날린 블록커 및 이뇨제로 구성된 군에서 선택된 것인 증상을 치료 또는 예방하는 방법.
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EP1852433B1 (en) * | 2004-10-29 | 2011-11-23 | Zeria Pharmaceutical Co., Ltd. | Carbazole derivative, solvate thereof, or pharmaceutically acceptable salt thereof |
US20090197947A1 (en) * | 2008-02-01 | 2009-08-06 | The Research Foundation Of State University Of New York | Medicaments and methods for lowering plasma lipid levels and screening drugs |
CN105801468B (zh) * | 2014-12-31 | 2018-08-17 | 深圳微芯生物科技股份有限公司 | 一种苯丙氨酸类化合物的盐及其无定形体 |
CN112479977B (zh) * | 2016-09-27 | 2022-07-19 | 深圳微芯生物科技股份有限公司 | 一种取代的苯基丙酸化合物对映异构体及其制备方法、组合物和应用 |
CN110467560A (zh) * | 2018-05-09 | 2019-11-19 | 深圳微芯生物科技股份有限公司 | 一种苯基氨基丙酸钠衍生物、其制备方法和应用 |
CN112516137A (zh) * | 2019-09-19 | 2021-03-19 | 深圳微芯生物科技股份有限公司 | 西格列羧及其衍生物用于伴有脂代谢异常的2型糖尿病治疗的用途 |
CN111437393B (zh) * | 2020-04-30 | 2021-03-02 | 深圳微芯生物科技股份有限公司 | 用于糖尿病及其并发症治疗的联合用药及其药物组合物 |
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GB9604242D0 (en) * | 1996-02-28 | 1996-05-01 | Glaxo Wellcome Inc | Chemical compounds |
KR100517644B1 (ko) * | 1997-10-27 | 2005-09-28 | 닥터 레디스 레보러터리즈 리미티드 | 신규의 삼원 화합물 및 그 약학적 용도, 그 제조방법 및이들을 포함하는 약제학적 조성물 |
US6440961B1 (en) * | 1997-10-27 | 2002-08-27 | Dr. Reddy's Research Foundation | Tricyclic compounds and their use in medicine: process for their preparation and pharmaceutical compositions containing them |
WO1999019313A1 (en) | 1997-10-27 | 1999-04-22 | Dr. Reddy's Research Foundation | Novel tricyclic compounds and their use in medicine; process for their preparation and pharmaceutical compositions containing them |
GB9817118D0 (en) | 1998-08-07 | 1998-10-07 | Glaxo Group Ltd | Pharmaceutical compounds |
EP1123297A1 (en) | 1998-10-21 | 2001-08-16 | Novo Nordisk A/S | New compounds, their preparation and use |
EP1123279A1 (en) | 1998-10-21 | 2001-08-16 | Novo Nordisk A/S | New compounds, their preparation and use |
JP2002527501A (ja) * | 1998-10-21 | 2002-08-27 | ノボ ノルディスク アクティーゼルスカブ | 新規化合物、その製造及び利用 |
WO2000063190A1 (en) | 1999-04-20 | 2000-10-26 | Novo Nordisk A/S | New compounds, their preparation and use |
JP2003520838A (ja) | 2000-01-28 | 2003-07-08 | ノボ ノルディスク アクティーゼルスカブ | 新規化合物、それらの製造および使用。 |
US6632322B1 (en) | 2000-06-30 | 2003-10-14 | Lam Research Corporation | Switched uniformity control |
NZ529033A (en) * | 2001-05-15 | 2005-06-24 | F | Carboxylic acid substituted oxazole derivatives for use as PPAR-alpha and -gamma activators in the treatment of diabetes |
WO2003011834A1 (en) | 2001-07-30 | 2003-02-13 | Novo Nordisk A/S | Novel vinyl n-(2-benzoylphenyl)-l-tyrosine derivatives and their use as antidiabetics etc |
US20030055076A1 (en) * | 2001-07-30 | 2003-03-20 | Lone Jeppesen | Novel compounds, their preparation and use |
-
2003
- 2003-11-18 US US10/715,622 patent/US7268157B2/en not_active Expired - Lifetime
- 2003-11-21 DK DK03772525.6T patent/DK1569904T3/da active
- 2003-11-21 AU AU2003280154A patent/AU2003280154B2/en not_active Expired
- 2003-11-21 ES ES03772525T patent/ES2382312T3/es not_active Expired - Lifetime
- 2003-11-21 KR KR1020057008310A patent/KR20050075386A/ko active Search and Examination
- 2003-11-21 WO PCT/IB2003/005371 patent/WO2004048333A1/en active Application Filing
- 2003-11-21 EP EP03772525A patent/EP1569904B1/en not_active Expired - Lifetime
- 2003-11-21 CA CA2504718A patent/CA2504718C/en not_active Expired - Lifetime
- 2003-11-21 SI SI200332127T patent/SI1569904T1/sl unknown
- 2003-11-21 AT AT03772525T patent/ATE540925T1/de active
- 2003-11-21 JP JP2005510266A patent/JP4750556B2/ja not_active Expired - Fee Related
- 2003-11-21 PT PT03772525T patent/PT1569904E/pt unknown
-
2006
- 2006-03-07 HK HK06102981.1A patent/HK1083021A1/xx not_active IP Right Cessation
-
2007
- 2007-08-01 US US11/882,417 patent/US20080051321A1/en not_active Abandoned
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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KR20190049883A (ko) * | 2016-09-27 | 2019-05-09 | 쉔젠 칩스크린 바이오사이언스 씨오., 엘티디. | 페닐알라닌 화합물의 제조 방법 |
Also Published As
Publication number | Publication date |
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EP1569904A1 (en) | 2005-09-07 |
ES2382312T3 (es) | 2012-06-07 |
CA2504718C (en) | 2012-01-31 |
EP1569904B1 (en) | 2012-01-11 |
WO2004048333A1 (en) | 2004-06-10 |
US7268157B2 (en) | 2007-09-11 |
HK1083021A1 (en) | 2006-06-23 |
US20040142921A1 (en) | 2004-07-22 |
US20080051321A1 (en) | 2008-02-28 |
DK1569904T3 (da) | 2012-04-30 |
AU2003280154A1 (en) | 2004-06-18 |
CA2504718A1 (en) | 2004-06-10 |
ATE540925T1 (de) | 2012-01-15 |
JP4750556B2 (ja) | 2011-08-17 |
EP1569904A4 (en) | 2008-04-16 |
PT1569904E (pt) | 2012-04-19 |
AU2003280154B2 (en) | 2009-04-02 |
SI1569904T1 (sl) | 2012-06-29 |
JP2006519171A (ja) | 2006-08-24 |
CY1112622T1 (el) | 2016-02-10 |
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