KR970706242A - 우레아 유도체 및 ACAT-억제제로서 그의 용도(Urea derivatives and their use as ACAT-inhibitors) - Google Patents

우레아 유도체 및 ACAT-억제제로서 그의 용도(Urea derivatives and their use as ACAT-inhibitors)

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Publication number
KR970706242A
KR970706242A KR1019970702138A KR19970702138A KR970706242A KR 970706242 A KR970706242 A KR 970706242A KR 1019970702138 A KR1019970702138 A KR 1019970702138A KR 19970702138 A KR19970702138 A KR 19970702138A KR 970706242 A KR970706242 A KR 970706242A
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South Korea
Prior art keywords
alkyl
pyridyl
phenyl
group
lower alkyl
Prior art date
Application number
KR1019970702138A
Other languages
English (en)
Inventor
다케시 테라사와
아키라 다나카
도시유키 치바
히사시 다카수기
Original Assignee
후지야마 아키라
후지사와 야꾸힝 고교 가부시키가이샤
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
Priority claimed from GB9419970A external-priority patent/GB9419970D0/en
Priority claimed from GBGB9506720.3A external-priority patent/GB9506720D0/en
Priority claimed from GBGB9514021.6A external-priority patent/GB9514021D0/en
Application filed by 후지야마 아키라, 후지사와 야꾸힝 고교 가부시키가이샤 filed Critical 후지야마 아키라
Publication of KR970706242A publication Critical patent/KR970706242A/ko

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    • C07D207/32—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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Abstract

본 발명은 약제로서 유용한 다음 일반식(Ⅰ)의 우레아 유도체 및 그의 약제학적으로 허용되는 염에 관한 것이다.
상기 식에서, R1은 일반식의 그룹(여기에서, R4는 적합한 치환체(들)을 가질 수 있는 아릴등이고, Y는 결합, 저급 알킬렌, -0-등이다)이고, R2는 저급 알킬, 저급 알콕시(저급)알킬 등이며, R3는 적합한 치환체(들)을 가질 수 있는 아릴 등이고, n은 0 또는 1이다.

Description

우레아 유도체 및 ACAT-억제제로서 그의 용도 (Urea derivatives and their use as ACAT-inhibitors)
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (13)

  1. 일반식(Ⅰ)의 화합물 및 약제학적으로 허용되는 그의 염
    상기 식에서, R1은 일반식의 그룹 [여기에서, R4는 적합한 치환체(들)을 가질 수 있는 아릴 또는 적합한 치환체(들)을 가질 수 있는 헤테로사이클릭 그룹이고, Y는 결합, 저급 알킬렌, -S-, -O-,=CH-, -CONH-,(여기에서, R7은 저급 알킬이다), -NHSO2-, -SO2NH-, -SO2NHCO- 또는 -CONHSO2-이다, 또는 각각 적합한 치환체(들)을 가질 수 있는 티아졸릴, 이미다졸릴, 피라졸릴, 피리딜, 티에닐, 푸릴, 이속사졸릴 또는 크로마닐이며; R2는 저급 알킬, 저급 알콕시(저급)알킬, 사이클로알킬, 적합한 치환체(들)을 가질 수 있는 아르(저급)알킬, 헤테로사이클릭 그룹, 또는 헤테로사이클릭(저급)알킬이고; R3는 적합한 치환체(들)을 가질 수 있는 아릴 또는 적합한 치환체(들)을 가질 수 있는 헤테로사이클릭 그룹이며; n은 0 또는 1 이다.
  2. 제1항에 있어서, R1은 일반식의 그룹 [여기에서, R4는 할로겐, 저급 알킬, 디(저급)알킬아미노, 보호된 아미노, 시아노, 모노(또는 디 또는 트리)-아르(저급)알킬을 가질 수 있는 헤테로사이클릭 그룹, 하이드록시, 보호된 하이드록시 및 모노(또는 디 또는 트리) 할로(저급)알킬로 구성된 그룹중에서 선택된 1 내지 3개의 치환체(들)을 가질 수 있는 페닐;또는 각각 저급 알킬, 모노(또는 디 또는 트리) 아르(저급)알킬 및 옥소로 구성된 그룹중에서 선택된 1 내지 3개의 치환체(들)를 가질 수 있는 티에닐, 피라졸릴, 이미다졸릴, 트리아졸릴, 피리딜, 피롤릴, 테트라졸릴, 옥사졸릴, 티아졸릴, 옥사디아졸릴, 피페라지닐, 티아졸리디닐 또는 메틸렌디옥시페닐이고; Y는 결합, 저급 알킬렌, -S-, -O-,=CH-, -CONH-,(여기에서, R7은 저급 알킬이다), -NHSO2-, -SO2NH-, -SO2NHCO- 또는 -CONHSO2-이다], 또는 각각 저급 알킬, 하이드록시, 보호된 하이드록시, 페닐, 할로페닐, 페닐티오 및 피롤릴로 구성된 그룹중에서 선택된 1 내지 5개의 치환체(들)을 가질 수 있는 티아졸릴, 이미다졸릴, 피라졸릴, 피리딜, 티에닐, 푸릴, 이속사졸릴 또는 크로마닐이고; R2는 저급 알킬; 저급 알콕시(저급)알킬; 사이클로(C3-C7)알킬; 할로겐, 저급 알콕시 및 디(저급알킬) 아미노로 구성된 그룹중에서 선택된 1 내지 3개의 치환체(들)를 가질 수 있는 페닐(저급)알킬; 테트라하이드로피라닐; 또는 푸릴(저급)알킬이며; R3는 저급 알킬 및 할로겐으로 구성된 그룹중에서 선택된 1 내지 3개의 치환체(들)을 가질 수 있는 페닐; 각각 저급 알킬, 저급 알칼티오, 할로겐, 저급 알콕시, 저급 알킬설피닐 및 저급 알킬설포닐로 구성된 그룹중에서 선택된 1 내지 3개의 치환체(들)를 가질 수 있는 피리딜 또는 피리미디닐인 화합물.
  3. 제2항에 있어서, R1은 일반식의 그룹 [여기에서, R4는 할로겐, 저급 알킬, 디(저급)알킬아미노, 아실아미노, 시아노, 모노(또는 디 또는 트리)아르(저급)알킬을 가질 수 있는 테트라졸릴, 하이드록시, 저급 알콕시(저급)알콕시 및 모노(또는 디 또는 트리)할로(저급)알킬로 구성된 그룹중에서 선택된 1 내지 3개의 치환체(들)를 가질 수 있는 페닐; 또는 각각 저급 알킬, 페닐(저급)알킬), 트리페닐(저급)알킬 및 옥소로 구성된 그룹중에서 선택된 1 또는 2개의 치환체(들)를 가질 수 있는 티에닐, 피라졸릴, 이미다졸릴, 트리아졸릴, 피리딜, 피롤릴, 테트라졸릴, 옥사졸릴, 티아졸릴, 옥사디아졸릴, 피페라지닐, 티아졸리디닐 또는 메틸렌 디옥시페닐이고; Y는 결합, 저급 알킬렌, -S-, -O-,=CH-, -CONH-,(여기에서, R7은 저급 알킬이다), -NHSO2-, -SO2NH-, -SO2NHCO- 또는 -CONHSO2- 이다], 또는 각각 저급 알킬, 하이드록시, 아실옥시, 페닐, 할로페닐, 페닐티오 및 피롤릴로 구성된 그룹중에서 선택된 1 내지 5개의 치환체(들)를 가질 수 있는 티아졸릴, 이미다졸릴, 피라졸릴, 피리딜, 티에닐, 푸릴, 이속사졸릴 또는 크로마닐이고; R2는 저급 알킬; 저급 알콕시(저급)알킬; 사이클로(C3-C7) 알킬; 할로겐, 저급 알콕시 및 디(저급알킬) 아미노로 구성된 그룹중에서 선택된 1 내지 2개의 치환체(들)을 가질 수 있는 페닐(저급)알킬 ; 테트라하이드로피라닐 또는 푸릴(저급)알킬이며; R3는 저급 알킬 및 할로겐으로 구성된 그룹중에서 선택된 2 또는 3개의 치환체(들)를 가질 수 있는 페닐; 각각 저급 알킬, 저급 알킬티오, 할로겐, 저급 알콕시, 저급 알킬설피닐 및 저급 알킬설포닐로 구성된 그룹중에서 선택된 2 또는 3개의 치환체(들)을 가질 수 있는 피리딜 또는 피리미디닐인 화합물.
  4. 제3항에 있어서, R1은 일반식의 그룹 [여기에서, R4는 할로겐, 저급 알킬페닐; 디(저급)알킬아미노페닐; 저급알킬포닐아미노페닐; 시아노페닐; 테트라졸릴페닐; (트리페닐(저급)알킬테트라졸릴)페닐; 트리할로(저급)알킬페닐; 두개의 저급 알킬 및 하이드록시를 갖는 페닐; 두개의 저급 알킬 및 저급 알콕시(저급)알콕시를 갖는 페닐; 티에닐; 저급 알킬 또는 트리페닐(저급)알킬을 가질 수 있는 피라졸릴; 이미다졸릴; 저급 알킬 및 페닐(저급)알킬로 구성된 그룹중에서 선택된 1 또는 2개의 치환체(들)를 가질 수 있는 트리아졸릴; 피리딜; 피롤릴; 저급 알킬 또는 트리페닐(저급)알킬을 가질 수 있는 테트라졸릴; 옥사졸릴; 저급 알킬티아졸릴; 저급 알킬옥사디아졸릴; 저급 알킬피페라지닐; 디옥소티아졸리디닐 또는 메틸렌디옥시페닐이고; Y는 결합, 저급 알킬렌, -S-, -O-,=CH-, -CONH-,(여기에서, R7은 저급 알킬이다), -NHSO2-, -SO2NH-, -SO2NHCO- 또는 -CONHSO2-이다]; 할로페닐티아졸릴; 페닐이미다졸릴; 페닐피라졸릴; 페닐피리딜; 페닐티오피리딜; 피롤릴피리딜; 페닐티에닐; 페닐푸릴; 페닐이속사졸릴; 또는 4개의 저급 알킬 및 하이드록시를 갖는 크로마닐이고; R2는 저급 알킬; 저급 알콕시(저급)알킬); 사이클로(C3-C7) 알킬, 페닐(저급)알킬; 할로페닐(저급)알킬; 저급 알콕시페닐(저급)알킬, 디(저급 알킬) 아미노페닐(저급)알킬, 테트라하이드로피라닐 또는 푸릴(저급)알킬이며; R3는 두개의 저급 알킬티오 및 저급 알킬을 갖는 피리딜; 할로겐, 저급 알킬 및 저급 알킬티오를 갖는 피리딜; 트리(저급 알킬) 피리딜; 두개의 저급 알콕시 및 저급알킬을 갖는 피리딜; 저급 알콕시, 저급 알칼티오 및 저급 알킬을 갖는 피리딜; 두개의 저급 알킬설피닐 및 저급 알킬을 갖는 피리딜; 두개의 저급 알킬설포닐 및 저급 알킬을 갖는 피리딜; 저급 알킬티오, 저급 알콕시 및 저급 알킬을 갖는 피리딜; 저급 알칼설피닐, 저급 알칼설포닐 및 저급 알킬을 갖는 피리딜; 저급 알킬티오, 저급 알킬설포닐 및 저급 알킬을 갖는 피리딜; 두개의 할로겐 및 저급 알킬을 갖는 피리딜; 디(저급)알콕시 피리미디닐; 또는 두개의 저급 알킬티오 및 저급 알킬을 갖는 피리미디닐인 화합물.
  5. 제4항에 있어서, R1은 일반식의 그룹 [여기에서, R4는 페닐 또는 할로페닐이고, Y는 -0-이다)이고, R2는 사이클로(C3-C7) 알킬 또는 페닐(저급)알킬이며; R3는 두개의 저급 알킬티오 및 저급 알킬을 갖는 페닐; 트리(저급 알킬) 피리딜; 두개의 할로겐 및 저급 알킬을 갖는 피리딜; 할로겐, 저급 알킬 및 저급 알칼티오를 갖는 피리딜; 저급 알킬티오, 저급 알콕시 및 저급 알킬을 갖는 피리딜; 저급 알킬티오, 저급 알킬 설포닐 및 저급 알킬을 갖는 피리딜; 두개의 저급 알킬설포닐 및 저급 알킬을 갖는 피리딜; 또는 두개의 저급 알킬티오 및 저급 알킬을 갖는 피리미디닐이고; n은 1인 화합물.
  6. 제5항에 있어서, R1은 일반식의 그룹 [여기에서, R4는 할로페닐이고, Y는 -0-이다)이고, R2는 사이클로(C3-C7) 알킬이며, R3는 트리(저급 알킬)피리딜; 또는 두개의 저급 알킬설포닐 및 저급 알킬을 갖는 피리딜인 화합물.
  7. 제4항에 있어서, R1은 일반식의 그룹 [여기에서, R4는 피라졸릴이고, Y는 결합이다)이고, R2는 페닐(저급)알킬, 저급 알콕시페닐(저급)알킬, 할로페닐(저급)알킬, 디(저급)알킬아미노페닐(저급)알킬 또는 사이클로(C3-C7)알킬이며; R3는 두개의 저급 알킬티오 및 저급 알킬을 갖는 피리딜; 할로겐, 저급 알킬 및 저급 알킬티오를 갖는 피리딜; 또는 두개의 저급 알킬티오 및 저급 알킬을 갖는 피리미디닐이고; n은 1인 화합물.
  8. 제7항에 있어서, R1은 일반식의 그룹 [여기에서, R4는 피라졸릴이고, Y는 결합이다)이고, R2는 페닐(저급)알킬이며; R3는 두개의 저급 알킬티오 및 저급 알킬을 갖는 피리딜인 화합물.
  9. (1)일반식(Ⅱ)의 화합물 또는 그의 염을 일반식(Ⅲ)의 화합물 또는 그의 염과 반응시켜 일반식(Ⅰ)의 화합물 또는 그의 염을 수득하거나, (2) 일반식(Ⅱ)의 화합물 또는 그의 염 및 일반식(Ⅳ)의 화합물 또는 그의 염에 대해 우레이도 그룹을 형성시켜 일반식(Ⅰ)의 화합물 또는 그의 염을 수득하거나, (3) 일반식(1a)의 화합물 또는 그의 염을 산화 반응시켜 일반식(Ⅰ)의 화합물 또는 그의 염을 수득함을 특징으로 하여, 일반식(Ⅰ)의 화합물 또는 그의 염을 제조하는 방법.
    상기 식에서, R1은 일반식의 그룹 [여기에서, R4는 적합한 치환체(들)을 가질 수 있는 아릴 또는 적합한 치환체(들)을 가질 수 있는 헤테로사이클릭 그룹이고, Y는 결합, 저급 알킬렌, -S-, -O-,=CH-, -CONH-,(여기에서, R7은 저급 알킬이다), -NHSO2-, -SO2NH-, -SO2NHCO- 또는 -CONHSO2-이다), 또는 각각 적합한 치환체(들)을 가질 수 있는 티아졸릴, 이미디졸릴, 파라졸릴, 피리딜, 티에닐, 푸릴, 이속사졸릴 또는 크로마닐이며; R2는 저급 알킬, 저급 알콕시(저급)알킬, 사이클로알킬, 적합한 치환체(들)을 가질 수 있는 아르(저급)알킬, 헤테로사이클릭 그룹, 또는 헤테로사이클릭(저급)알킬이고; R3는 적합한 치환체(들)을 가질 수 있는 아릴 또는 적합한 치환체(들)을 가질 수 있는 헤테로사이클릭 그룹이며; n은 0 또는 1이고; Ra 3는 두개의 저급 알킬티오 및 저급 알킬을 갖는 피리딜이며; Rb 3는 두개의 저급 알킬설포닐 및 저급 알킬을 갖는 피리딜; 두개의 저급 알칼설피닐 및 저급 알킬을 갖는 피리딜; 또는 저급 알킬설포닐, 저급 알킬설피닐 및 저급 알킬을 갖는 피리딜이다.
  10. 약제학적으로 허용되는 실질적으로 무독성인 담체 또는 부형제와의 혼합물로, 활성 성분으로서 제1항의 화합물을 함유하는 약제학적 조성물.
  11. 의약으로서 사용하기 위한 제1항의 화합물.
  12. 유효량의 제1항의 화합물을 인간 또는 동물에게 투여함을 특징으로하여, 고콜레스테롤혈증, 고지혈증, 동맥경화증 또는 이들에 의해 유발된 질환을 치료 및/또는 예방하는 방법.
  13. 인간 또는 동물에게서 고콜레스테롤혈증, 고지혈증, 동맥경화증 또는 이들에 의해 유발된 질환을 치료 및/또는 예방하기 위한 약제를 제조하기 위한 제1항의 화합물의 용도.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019970702138A 1994-10-04 1995-09-29 우레아 유도체 및 ACAT-억제제로서 그의 용도(Urea derivatives and their use as ACAT-inhibitors) KR970706242A (ko)

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GB9419970A GB9419970D0 (en) 1994-10-04 1994-10-04 Urea derivatives
GB9419970.0 1994-10-04
GBGB9506720.3A GB9506720D0 (en) 1995-03-31 1995-03-31 Urea derivatives
GB9506720.3 1995-03-31
GB9514021.6 1995-07-10
GBGB9514021.6A GB9514021D0 (en) 1995-07-10 1995-07-10 Urea derivatives
PCT/JP1995/001982 WO1996010559A1 (en) 1994-10-04 1995-09-29 Urea derivatives and their use as acat-inhibitors

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Families Citing this family (86)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU712467B2 (en) * 1995-09-18 1999-11-04 Sankyo Company Limited New urea derivatives having ACAT inhibitory activity, their preparation and their therapeutic and prophylactic use
DE19742951A1 (de) 1997-09-29 1999-04-15 Hoechst Schering Agrevo Gmbh Acylsulfamoylbenzoesäureamide, diese enthaltende nutzpflanzenschützende Mittel und Verfahren zu ihrer Herstellung
AU751139B2 (en) 1997-10-13 2002-08-08 Astellas Pharma Inc. Amide derivative
KR100571588B1 (ko) * 1997-12-22 2006-04-17 바이엘 코포레이션 치환 헤테로시클릭 우레아를 이용한 ｒａｆ 키나제의 억제
US6452008B2 (en) 1998-02-25 2002-09-17 Sumitomo Pharmaceuticals Company, Limited Pyridone derivatives and process for preparing the same
AU2547399A (en) * 1998-02-25 1999-09-15 Sumitomo Pharmaceuticals Company, Limited Pyridone derivatives and process for producing the same
US6617351B1 (en) 1998-07-31 2003-09-09 Eli Lilly And Company Amide, carbamate, and urea derivatives
PE20000942A1 (es) * 1998-07-31 2000-09-28 Lilly Co Eli Derivados de amida, carbamato y urea
US8124630B2 (en) 1999-01-13 2012-02-28 Bayer Healthcare Llc ω-carboxyaryl substituted diphenyl ureas as raf kinase inhibitors
EP1158985B1 (en) 1999-01-13 2011-12-28 Bayer HealthCare LLC OMEGA-CARBOXY ARYL SUBSTITUTED DIPHENYL UREAS AS p38 KINASE INHIBITORS
CA2360740A1 (en) 1999-03-02 2000-09-08 Boehringer Ingelheim Pharmaceuticals, Inc. Compounds useful as reversible inhibitors of cathepsin s
US6503949B1 (en) 1999-05-17 2003-01-07 Noro Nordisk A/S Glucagon antagonists/inverse agonists
US6420364B1 (en) 1999-09-13 2002-07-16 Boehringer Ingelheim Pharmaceuticals, Inc. Compound useful as reversible inhibitors of cysteine proteases
US6849660B1 (en) 2000-08-01 2005-02-01 Isis Pharmaceuticals, Inc. Antimicrobial biaryl compounds
JO2654B1 (en) 2000-09-04 2012-06-17 شركة جانسين فارماسوتيكا ان. في Multiple aryl caroxa amides are useful as lipid - lowering agents
JO2409B1 (en) 2000-11-21 2007-06-17 شركة جانسين فارماسوتيكا ان. في Second-phenyl carboxy amides are useful as lipid-lowering agents
ATE386716T1 (de) * 2000-12-26 2008-03-15 Pola Pharma Inc Biphenylderivate
JO2390B1 (en) 2001-04-06 2007-06-17 شركة جانسين فارماسوتيكا ان. في Diphenylcarboxamides act as lipid-lowering agents
EP1466904A4 (en) 2001-12-28 2005-12-14 Takeda Pharmaceutical BIARYL CONNECTION AND ITS USE
ATE529406T1 (de) 2002-02-11 2011-11-15 Bayer Healthcare Llc Aryl-harnstoffe als kinase inhibitoren
SI1478358T1 (sl) 2002-02-11 2013-09-30 Bayer Healthcare Llc Sorafenib tozilat za zdravljenje bolezni, značilnih po abnormalni angiogenezi
PE20040167A1 (es) * 2002-03-28 2004-05-26 Novartis Ag Amidas del acido sulfamico
UA79300C2 (en) 2002-08-12 2007-06-11 Janssen Pharmaceutica Nv N-aryl piperidine substituted biphenylcarboxamides as inhibitors of apolipoprotein b secretion
ES2277142T3 (es) 2002-08-30 2007-07-01 Japan Tobacco Inc. Compuesto de dibencilamina y su uso medicinal.
JP4745666B2 (ja) * 2002-12-12 2011-08-10 興和株式会社 ヒドロキシアルキル環状ジアミン化合物
MXPA05007513A (es) 2003-01-14 2005-09-21 Cytokinetics Inc Compuestos, composiciones y metodos.
EP1491527A1 (en) * 2003-06-25 2004-12-29 Bayer CropScience GmbH Process for preparing acylsulfamoylbenzamides
KR101157272B1 (ko) 2003-07-22 2012-06-15 아레나 파마슈티칼스, 인크. 5?ｈｔ2ａ 세로토닌 수용체의 조절자로서 이와 관련된질환의 예방 및 치료에 유용한 디아릴 및 아릴헤테로아릴우레아 유도체
CL2004001834A1 (es) 2003-07-23 2005-06-03 Bayer Pharmaceuticals Corp Compuesto 4-{4-[3-(4-cloro-3-trifluorometilfenil)-ureido]-3-fluorofenoxi}-piridin-2-metilamida, inhibidor de la raf, vegfr, p38 y pdgfr quinasas, sus sales; composiicon farmaceutica; combinacion farmaceutica; y su uso para tratar trastornos hiperprol
CN100482649C (zh) 2003-09-17 2009-04-29 诺瓦提斯公司 有机化合物
US7829552B2 (en) 2003-11-19 2010-11-09 Metabasis Therapeutics, Inc. Phosphorus-containing thyromimetics
CN1926114B (zh) 2004-03-23 2011-08-24 艾尼纳制药公司 用于制备经取代n-芳基-n′-′3-(1h-吡唑-5-基)苯基脲及其中间体的方法
WO2005115990A1 (ja) 2004-05-26 2005-12-08 Eisai R & D Management Co., Ltd. シンナミド化合物
BRPI0512193B8 (pt) 2004-06-17 2021-05-25 Cytokinetics Inc composto ou sal farmaceuticamente aceitável, composição farmacêutica, e, uso do composto ou sal
US7176222B2 (en) 2004-07-27 2007-02-13 Cytokinetics, Inc. Syntheses of ureas
CN100577657C (zh) 2004-10-26 2010-01-06 卫材R&D管理有限公司 肉桂酰胺化合物的无定形物
KR101021828B1 (ko) 2004-10-27 2011-03-17 다이이찌 산쿄 가부시키가이샤 2 이상의 치환기를 갖는 벤젠 화합물
PE20061130A1 (es) 2004-11-19 2007-01-05 Arena Pharm Inc Derivados de 3-fenil-pirazol como moduladores del receptor de serotonina 5-ht2a
US7538223B2 (en) 2005-08-04 2009-05-26 Cytokinetics, Inc. Compounds, compositions and methods
US7741317B2 (en) 2005-10-21 2010-06-22 Bristol-Myers Squibb Company LXR modulators
JP2009512715A (ja) 2005-10-21 2009-03-26 ノバルティス アクチエンゲゼルシャフト レニン阻害剤と抗異脂肪血症剤および／または抗肥満症剤の組み合わせ
US7888376B2 (en) 2005-11-23 2011-02-15 Bristol-Myers Squibb Company Heterocyclic CETP inhibitors
TWI370130B (en) 2005-11-24 2012-08-11 Eisai R&D Man Co Ltd Two cyclic cinnamide compound
CA2629745A1 (en) 2005-11-24 2007-05-31 Eisai R & D Management Co., Ltd. Morpholine type cinnamide compound
US7825120B2 (en) 2005-12-15 2010-11-02 Cytokinetics, Inc. Certain substituted ((piperazin-1-ylmethyl)benzyl)ureas
TW200808321A (en) 2005-12-15 2008-02-16 Cytokinetics Inc Certain chemical entities, compositions and methods
WO2007078815A2 (en) 2005-12-16 2007-07-12 Cytokinetics, Inc. Certain chemical entities, compositions, and methods
EP1962852B1 (en) 2005-12-19 2017-01-25 Cytokinetics, Inc. Compounds, compositions and methods
TWI378091B (en) 2006-03-09 2012-12-01 Eisai R&D Man Co Ltd Multi-cyclic cinnamide derivatives
WO2007136680A2 (en) 2006-05-18 2007-11-29 Arena Pharmaceuticals, Inc. 3-pyraz0lyl-benzamide-4-ethers, secondary amines and derivatives thereof as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto
EP2018371B1 (en) 2006-05-18 2015-03-04 Arena Pharmaceuticals, Inc. Primary amines and derivatives thereof as modulators of the 5-ht2a serotonin receptor useful for the treatment of disorders related thereto
MY154962A (en) 2006-05-18 2015-08-28 Arena Pharm Inc Crystalline forms and processes for the preparation of phenyl-pyrazoles useful as modulators of the 5-ht2a seratonin receptor
CN101448793A (zh) * 2006-05-19 2009-06-03 卫材R&D管理有限公司 脲型肉桂酰胺衍生物
CN100390150C (zh) * 2006-06-05 2008-05-28 吴汝林 盐酸咪唑苯脲的制备方法
AR062095A1 (es) 2006-07-28 2008-10-15 Eisai R&D Man Co Ltd Profarmaco de compuesto cinamida
TWI415845B (zh) 2006-10-03 2013-11-21 Arena Pharm Inc 用於治療與５-ｈｔ2ａ血清素受體相關聯病症之作為５-ｈｔ2ａ血清素受體之調節劑的吡唑衍生物
JP5498168B2 (ja) 2006-12-01 2014-05-21 ブリストル−マイヤーズ スクイブ カンパニー アテローム性動脈硬化および循環器疾患の治療のためのｃｅｔｐ阻害剤としてのｎ−（（３−ベンジル）−２，２−（ビス−フェニル）−プロパン−１−アミン誘導体
TW200840566A (en) * 2006-12-22 2008-10-16 Esteve Labor Dr Heterocyclyl-substituted-ethylamino-phenyl derivatives, their preparation and use as medicaments
TW200848054A (en) 2007-02-28 2008-12-16 Eisai R&D Man Co Ltd Two cyclic oxomorpholine derivatives
US9567327B2 (en) 2007-08-15 2017-02-14 Arena Pharmaceuticals, Inc. Imidazo[1,2-a]pyridine derivatives as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto
US7935815B2 (en) 2007-08-31 2011-05-03 Eisai R&D Management Co., Ltd. Imidazoyl pyridine compounds and salts thereof
KR20100055456A (ko) 2007-08-31 2010-05-26 에자이 알앤드디 매니지먼트 가부시키가이샤 다환식 화합물
US20110021538A1 (en) 2008-04-02 2011-01-27 Arena Pharmaceuticals, Inc. Processes for the preparation of pyrazole derivatives useful as modulators of the 5-ht2a serotonin receptor
EP3025727A1 (en) 2008-10-02 2016-06-01 The J. David Gladstone Institutes Methods of treating liver disease
CN104784173B (zh) 2008-10-28 2019-07-26 艾尼纳制药公司 用于治疗5-ht2a5-羟色胺受体相关障碍的5-ht2a5-羟色胺受体调节剂组合物
US9126946B2 (en) 2008-10-28 2015-09-08 Arena Pharmaceuticals, Inc. Processes useful for the preparation of 1-[3-(4-bromo-2-methyl-2H-pyrazol-3-yl)-4-methoxy-phenyl]-3-(2,4-difluoro-phenyl)urea and crystalline forms related thereto
WO2010093601A1 (en) 2009-02-10 2010-08-19 Metabasis Therapeutics, Inc. Novel sulfonic acid-containing thyromimetics, and methods for their use
FR2946346B1 (fr) 2009-06-05 2011-05-20 Galderma Res & Dev Nouveaux derives dioxo-imidazolidine, inhibiteurs de l'enzyme soat-1, compositions pharmaceutiques et cosmetiques les contenant.
FR2946340B1 (fr) 2009-06-05 2011-06-24 Galderma Res & Dev Nouveaux n-phenyl acetamie, inhibiteurs de l'enzyme soat-1, compositions pharmaceutiques et cosmetiques les contenant.
FR2946345B1 (fr) 2009-06-05 2011-05-20 Galderma Res & Dev Nouveaux derives dioxo-imidazolidine, inhibiteurs de l'enzyme soat-1, compositions pharmaceutiques et cosmetiques les contenant.
FR2946342B1 (fr) 2009-06-05 2011-06-24 Galderma Res & Dev Nouveaux derives de dioxo-imidazolidine, inhibiteurs de l'enzyme soat-1, compositions pharmaceutiques et cosmetiques les contenant.
US8980891B2 (en) 2009-12-18 2015-03-17 Arena Pharmaceuticals, Inc. Crystalline forms of certain 3-phenyl-pyrazole derivatives as modulators of the 5-HT2A serotonin receptor useful for the treatment of disorders related thereto
WO2011145022A1 (en) 2010-05-21 2011-11-24 Pfizer Inc. 2-phenyl benzoylamides
US20130156720A1 (en) 2010-08-27 2013-06-20 Ironwood Pharmaceuticals, Inc. Compositions and methods for treating or preventing metabolic syndrome and related diseases and disorders
US20130345392A1 (en) 2011-03-04 2013-12-26 Pfizer Inc Edn3-like peptides and uses thereof
US9181261B2 (en) * 2012-05-22 2015-11-10 Merck Sharp & Dohme Corp. TrkA kinase inhibitors, compositions and methods thereof
WO2013185284A1 (en) 2012-06-12 2013-12-19 Abbott Laboratories Pyridinone and pyridazinone derivatives
CN104602690A (zh) * 2012-08-29 2015-05-06 默克专利股份有限公司 用于治疗骨关节炎的ddr2抑制剂
EA201590696A1 (ru) * 2012-11-06 2015-08-31 Эли Лилли Энд Компани Новые бензилсульфонамидные соединения, подходящие в качестве ингибиторов mogat-2
MX2015011676A (es) * 2013-03-14 2016-04-25 Celtaxsys Inc Inhibidores de leucotrieno a4 hidrolasa.
JP2016516804A (ja) 2013-04-17 2016-06-09 ファイザー・インク 心血管疾患を治療するためのｎ−ピペリジン−３−イルベンズアミド誘導体
DK3054936T5 (da) 2013-10-10 2024-03-18 Eastern Virginia Medical School 4-((2-hydroxy-3-methoxybenzyl)amino) benzensulfonamid derivater som 12-lipoxygenase inhibitorer
WO2016055901A1 (en) 2014-10-08 2016-04-14 Pfizer Inc. Substituted amide compounds
EP4119141A1 (en) 2015-06-12 2023-01-18 Axovant Sciences GmbH Nelotanserin for the prophylaxis and treatment of rem sleep behavior disorder
JP2018520187A (ja) 2015-07-15 2018-07-26 アクソヴァント サイエンシーズ ゲゼルシャフト ミット ベシュレンクテル ハフツングAxovant Sciences GmbH 神経変性疾患と関連する幻覚の予防および処置のために有用な５−ｈｔ２ａセロトニン受容体のモジュレーターとしてのジアリールおよびアリールヘテロアリール尿素誘導体
JOP20210193A1 (ar) 2019-01-18 2023-01-30 Astrazeneca Ab مثبطات pcsk9 وطرق استخدامها

Family Cites Families (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE2132431A1 (de) * 1971-06-30 1973-01-11 Riedel De Haen Ag 4-phenyl-thiazolderivate enthaltende pharmazeutische praeparate
GB1598900A (en) * 1978-05-23 1981-09-23 Lilly Industries Ltd Heterocyclic amino derivatives
US4623662A (en) * 1985-05-23 1986-11-18 American Cyanamid Company Antiatherosclerotic ureas and thioureas
GB8827152D0 (en) * 1988-11-21 1988-12-29 Wellcome Found Anti-atherosclerotic diaryl compounds
AU632809B2 (en) * 1989-05-25 1993-01-14 Takeda Chemical Industries Ltd. Benzocycloalkane benzopyran and benzothiopyran urea derivatives and production thereof
FR2661676A1 (fr) * 1990-05-02 1991-11-08 Lipha Derives d'amino benzocycloalcanes, procedes de preparation et medicaments les contenant.
US5169844A (en) * 1991-12-20 1992-12-08 American Home Products Corporation 4-substituted piperidinecarboxylic acid esters: inhibition of cholesterol absorption
US6001860A (en) * 1992-05-28 1999-12-14 Pfizer Inc. N-aryl and N-heteroarylurea derivatives as inhibitors of acyl coenzyme A: Cholesterol acyl transferase (ACAT)
FR2692575B1 (fr) * 1992-06-23 1995-06-30 Sanofi Elf Nouveaux derives du pyrazole, procede pour leur preparation et compositions pharmaceutiques les contenant.
JP3116256B2 (ja) * 1993-01-14 2000-12-11 小野薬品工業株式会社 （チオ）ウレア誘導体

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IL115483A0 (en) 1996-01-19
CA2200981A1 (en) 1996-04-11
AU3577995A (en) 1996-04-26

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