KR920006298A - 피브리노겐 수용체 길항제 - Google Patents

피브리노겐 수용체 길항제 Download PDF

Info

Publication number
KR920006298A
KR920006298A KR1019910016837A KR910016837A KR920006298A KR 920006298 A KR920006298 A KR 920006298A KR 1019910016837 A KR1019910016837 A KR 1019910016837A KR 910016837 A KR910016837 A KR 910016837A KR 920006298 A KR920006298 A KR 920006298A
Authority
KR
South Korea
Prior art keywords
propionic acid
phenyl
mammal
compound
alkyl
Prior art date
Application number
KR1019910016837A
Other languages
English (en)
Inventor
에스. 이그버트슨 멜리사
디. 하트만 죠지
할젠코 와실
엘. 라스웰 윌리암
Original Assignee
제임스 에프. 노턴
머크 앤드 캄파니, 인코포레이티드
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 제임스 에프. 노턴, 머크 앤드 캄파니, 인코포레이티드 filed Critical 제임스 에프. 노턴
Publication of KR920006298A publication Critical patent/KR920006298A/ko

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C235/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms
    • C07C235/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton
    • C07C235/04—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated
    • C07C235/12—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by oxygen atoms having carbon atoms of carboxamide groups bound to acyclic carbon atoms and singly-bound oxygen atoms bound to the same carbon skeleton the carbon skeleton being acyclic and saturated having the nitrogen atom of at least one of the carboxamide groups bound to an acyclic carbon atom of a hydrocarbon radical substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
    • C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
    • C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
    • C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
    • C07D295/088—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings to an acyclic saturated chain
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P7/00—Drugs for disorders of the blood or the extracellular fluid
    • A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C317/00—Sulfones; Sulfoxides
    • C07C317/26—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C317/28—Sulfones; Sulfoxides having sulfone or sulfoxide groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton with sulfone or sulfoxide groups bound to acyclic carbon atoms of the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C325/00—Thioaldehydes; Thioketones; Thioquinones; Oxides thereof
    • C07C325/02—Thioketones; Oxides thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C07C327/20—Esters of monothiocarboxylic acids
    • C07C327/22—Esters of monothiocarboxylic acids having carbon atoms of esterified thiocarboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C327/00—Thiocarboxylic acids
    • C07C327/38—Amides of thiocarboxylic acids
    • C07C327/48—Amides of thiocarboxylic acids having carbon atoms of thiocarboxamide groups bound to carbon atoms of six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
    • C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D211/06—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
    • C07D211/08—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms
    • C07D211/18—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D211/20—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms
    • C07D211/22—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hydrocarbon or substituted hydrocarbon radicals directly attached to ring carbon atoms with substituted hydrocarbon radicals attached to ring carbon atoms with hydrocarbon radicals, substituted by singly bound oxygen or sulphur atoms by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
    • C07F9/3882—Arylalkanephosphonic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
    • C07F9/576—Six-membered rings
    • C07F9/60—Quinoline or hydrogenated quinoline ring systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/645—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having two nitrogen atoms as the only ring hetero atoms
    • C07F9/6509—Six-membered rings
    • C07F9/650952—Six-membered rings having the nitrogen atoms in the positions 1 and 4
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65583—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system each of the hetero rings containing nitrogen as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6558—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system
    • C07F9/65586—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing at least two different or differently substituted hetero rings neither condensed among themselves nor condensed with a common carbocyclic ring or ring system at least one of the hetero rings does not contain nitrogen as ring hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/06—Systems containing only non-condensed rings with a five-membered ring
    • C07C2601/08—Systems containing only non-condensed rings with a five-membered ring the ring being saturated
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2601/00—Systems containing only non-condensed rings
    • C07C2601/12—Systems containing only non-condensed rings with a six-membered ring
    • C07C2601/14—The ring being saturated

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Veterinary Medicine (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Peptides Or Proteins (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Hydrogenated Pyridines (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Heterocyclic Compounds Containing Sulfur Atoms (AREA)
  • Quinoline Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

내용 없음

Description

피브리노겐 수용체 길항제
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (36)

  1. 하기 일반식(Ⅰ)의 화합물 및 이의 약제학적으로 허용가능한 염.
    상기 식에서 R1은, 1,2,3 또는 4개의 헤테로원자를 함유하는 4내지 8원의 헤테로사이클릭 환헤테로사이클릭 환은(여기에서 헤테로 원자는 N, O 또는 S이며, 헤테로 사이클릭 환은 어떤 원자에서든 H, R6또는 R7에 의해 임의로 치환된다.
    NR6R7[여기에서, R6및 R7은 독립적으로 수소, C1-10알콕시카보닐 또는 비치환 또는 치환된 C1-10알킬 및 사이클로알킬이며, 여기에서, 치환체는, C1-10알콕시, C1-10알콕시알킬, C1-10알콕시알킬옥시,C1-10알콕시카보닐, C1-10알킬카보닐, C0-5알킬아미노카보닐, C1-10아르알킬카보닐, C4-10아르알킬티오카보닐 티오카보닐, C1-10알콕시티오카보닐, 아릴, 1,2,3 또는 4개의 헤테로원자를 함유하는 5내지 6원 포화 헤테로사이클릭 환(여기에서, 상기 헤테로원자는 N, 0 및 S중에서 선택된다), C1-4알카노일아미노, C1-6알콕시카보닐-C0-6알킬아미노, C1-10알킬설포닐아미노, C4-10아르알킬설포닐아미노, C4-10아르알킬, C1-10알크아릴, C1-10알킬티오, C4-10아르알킬티오, C1-10알킬설피닐, C4-10아르알킬설피닐, C1-10알킬설포닐, C4-10아르알킬설포닐, 아미노설포닐, C1-10알킬아미노설포닐, C4-10아르알킬설포닐 아미노, 옥소, 티오, 비치환 또는 일-또는 이치환된 1-에테닐, 2-에테닐, 2-에테닐 또는 3-프로페닐(여기에서, 치환체는 수소, C1-10알킬, 및 C7-10아르알킬 중에서 선택된다.카복시, 하이드록시, 아미노, C1-6알킬아미노, C1-6디알킬아미노,할로겐(여기에서 할로겐은 C1, F, Br, 또는 I이다). 니트로 또는 시아노이며, 또한 N은 상기에서 R6및 R7에 대해 정의한 바와 같은 치환체에 의해 추가로 치환되어 4급 암모늄 이온을 형성할수 있다]이고; R2및 R3는 독립적으로 수소, 아릴 또는 비치환 또는 치환된 C1-10알킬 또는 사이클로알킬, [여기에서, 치환체는 C1-10알콕시알킬, 아릴, 1,2,3 또는 4개의 헤테로원자를 함유하는 내지 8원의 헤테로사이클릭 환(여기에서, 상기 헤테로원자는, N, O 및 S중에서 선택된다.)
    C4-10아르알킬, C1-10알크아릴, 카복시, C1-10알킬카보닐, C1-10알킬티오카보닐, C4-10아르알킬카보닐, C4-10아르알킬티오카보닐, C1-5알콜시카보닐, C4-10아르알콕시카보닐, C1-5알콕시, C4-10아르알콕시, C1-5알킬아미노, C1-12디알킬아미노, C1-5알킬아미노, C4-12아르알카노일아미노, C4-10아르알킬아미노이다]이고;R4는 수소, 아릴, C1-10알킬 또는 사이클로알킬, C4-10아르알킬, 아릴카보닐, 아미노카보닐, C1-10알킬카보닐, C1-6알킬아미노카보닐, C1-10알킬티오카보닐, C1-6디알킬아미노, 카보닐, C1-10알콕시티오카보닐, 아릴 C1-6알킬아미노카보닐, C1-10알콕시카보닐, C4-10아르알킬카보닐, C4-10아르알콕시카보닐, C1-10카복시알킬이고, 또한 치환체 R4는 ,R6에 대해 정의 한 그룹으로 부터 선택된 하나 이상의 치환체 또는 아미드 결합에 의해 연결된 L-또는 D-아미노산에 의해 치환될수 있으며; R5는 1,2,3 또는 4개의 헤테로원자를 함유하는 4내지 8원의 포화 또는 불포화 헤테로사이클릭 환(여기에서, 헤테로원자는 N, O 또는 S이다), 또는[여기에서, R8은 하이드록시, C1-10알킬옥시, C1-10알크아릴옥시, C4-10아르알킬옥시, C4-10아르알킬카보닐옥시, C1-10알콕시알킬옥시, C1-10알콕시알킬카보닐옥시, C1-10알콕시카보닐옥시알킬, C1-10알킬카보닐옥시알킬옥시 및 아미드 결함에 의해 연결된 L-또는 O-아미노산(여기에서, 이미노산의 카복실산 잔기는 유리산 이거나 C1-5알킬에 의해 에스테르화된다)이다],또는(여기에서 R9및 R10은 수소, C1-10알킬 및 C4-10아르알킬 중에서 선택된다)이고; X 및 Y는 독립적으로 NR6, O, SO, SO2,옥소, 아릴, 티오노, 비치환 또는 치환된 C1-15알킬 또는 사이클로알킬[여기에서, 치환체는 독립적으로 R6및 R7이다),SO2-, SO2-NR6-, 또는 1,2,3 또는 4개의 헤테로원자를 함유하는 4내지 8원의 헤테로사이클릭 환(여기서, 헤테로원자는, N, O 및 S이고, 환은 독립적으로 어떤 원자에서 R6로 치환된다)]이며; Z는 임의의 치환체이며, 존재할 경우, X 및 Y에 대해 정의한 그룹중에서 독립적으로 선택되고 ; m은 0내지 10의 정수이고; n은 0내지 10의 정수이며; p는 0내지 3의 정수이다.
  2. 하기 일반식(Ⅱ)의 화합물 및 이의 약제학적으로 허용가능한 염,
    상기 식에서 R1은, 1,2,3 또는 4개의 헤테로원자를 함유하는 4내지 8원의 헤테로사이클릭 환(여기에서 헤테로 원자는 N, O 또는 S이며, 헤테로 사이클릭 환은 수소, C1-10알킬에 의해 임의로 치환된)또는 NR6R7[여기에서 R6및 R7은 독립적으로, 수소, C1-10알콕시카보닐 또는 비치환 또는 치환된 C1-10알킬 (여기에서, 치환체는 C1-10알콕시 C1-10알콕시카보닐 아릴, C4-10아르알킬, C1-10알크아릴 카복시, 하이드록시 또는 아미노이다)].
    (여기에서, N은 추가로 치환되어 4급 암모늄 이온을 형성할수 있다)이고; R2및 R3는 독립적으로, 수소, C1-10알콕시카보닐, C1-10알콕시카보닐, C4-10아르알킬카보닐 또는 C4-10아르알콕시카보닐이고, 또한 치환체 R4는 제1항에서 R6로서 정의된 그룹으로부터의 하나 이상의 치환체로 치환될수 있으며, R11은 수소 또는 C1-10알킬이고, X 및 Y는 독립적으로, O, S, SO, SO2, 아릴, -CH=CH-, 옥소, -C-NR6, 또는NR6SO2, -SO2NR6-, 비치환 또는 치환된 C1-15직쇄 또는 측쇄 알킬(여기에서, 치환체는 카복시, 하이드록시, C1-10알콕시, 또는 N, O또는 S로부터 선택된, 1, 2 또는 3개의 헤테로원자를 함유하는 4- 내지 6-원 헤테로 사이클릭 환이다)이며; Z는 임의의 치환체이며, 존재할 경우, O, SO2, NR6CO, CONR6,이며; m은 0내지 6의 정수이고 ; n은 0내지 6의 정수이며; p는 0내지 3의 정수이다.
  3. 하기 일반식(Ⅱ)의 화합물 및 이의 약제학적으로 허용가능한 염.
    상기 식에서 R1은, 1 또는 2개의 헤테로원자를 함유하는 5내지 6원의 헤테로사이클릭 환환(여기에서 헤테로 원자는 N, O 또는 S이며, 헤테로 사이클릭 환은 수소, C1-5알킬에 의해 임의로 치환된)또는 NR6R7[여기에서 R6및 R7은 독립적으로, 수소, C1-10알콕시카보닐 또는 비치환 또는 치환된 C1-10알킬 여기에서, 상기 치환체는 C1-10알콕시카보닐, 아릴, C4-10아르알킬이다)이다].
    (여기에서, N은 추가로 치환되어 4급 암모늄 이온을 형성할수 있다)이고; R2및 R3는 수소, R4는 아릴카보닐, C1-10알킬카보닐, 아르알킬카보닐, 아르알킬카보닐, C1-10알킬카보닐, C4-10아르알킬카보닐, 또는 C4-10아르알콕시카보닐이며, 또한 치환체 R4는 제1항에서 R6에 대해 정의한 그룹으로부터의 하나 이상의 치환체로 치환될수 있으며; R11는 수소 또는 C1-10알킬이고; X 및 Y는 독립적으로, NR6SO2, -SO2NR6-, 비치환 또는 치환된 C1-15직쇄 또는 측쇄 알킬(여기에서, 치환체는 하이드록시거나, N, O또는 S로부터 선택된, 1 또는 2개의 헤테로원자를 함유하는 4- 내지 6-원 헤테로 사이클릭 환이다)이며; 직쇄 또는 측쇄 알킬이고, m은 0내지 6의 정수이고 ; n은 0내지 6의 정수이며; p는 0내지 3의 정수이다.
  4. 하기 일반식(Ⅲ)는 화합물 및 이의 약제학적으로 허용가능한 염.
    상기 식에서 R1은, 1 또는 2개의 헤테로원자를 함유하는 6원의 헤테로사이클릭 환(여기에서 헤테로 원자는 N이고, 헤테로 사이클릭 환은 C1-5알킬에 의해 임의로 치환된)또는 NR6R7[여기에서 R6및 R7은 독립적으로, 수소 또는 C1-10알킬이다)이고, R4는 아릴카보닐, C1-10알킬카보닐,C4-10아르알킬카보닐,C1-10알콕시카보닐,C4-10아르알킬카보닐,C4-10아르알콕시카보닐이고, 또한, 치환체 R4는 제1항에서 R6로서 정의한 그룹으로부터의 하나 이상의 치환체로 치환될수 있으며, X 및 Y는 독립적으로, O,SO2, 아릴,-CH=CH- 또는 C1-10직쇄 또는 측쇄 알킬이고, Z는 임의의 치환체이며, 존재할 경우, O, 또는 C1-5직쇄 또는 측쇄 알킬이며, m은 0내지 6의 정수이고; n은 1이고;p는 0이다.
  5. 제1항에 있어서,2-S-(6-N-벤질옥시카보닐아미노)-3-[4-(3-클로로프로필옥시페닐]프로피온산; 2-S-(N-벤질옥시카보닐아미노)-3-[4-(N,N,2,2-테트라메틸-1,3-프로판디아미노)프로필옥시페닐]프로피온산; 2-S-(N-벤질옥시카보닐아미노)-3-[4-(3-N-피톨리디닐프로필옥시)페닐]프로피온산;2-S-(N-벤질옥시카보닐아미노)-4-[3-(N-메틸-N-벤질아미노프로필옥시페닐)프로피온산; 2-S-(N-벤질옥시카보닐아미노)-3-[4-(4-피페라지닐)부틸옥시페닐]프로피온산; 2-S-(N-벤질옥시카보닐아미노)3-[4-(1,1,4,4-테트라메틸부틸아미노)필로필옥시페닐]프로피온산; 2-S-(N-벤질옥시카보닐아미노)-3-[4-(4-메틸피페라진-1-일)필로필옥시페닐]프로피온산; 2-S-(N-벤질옥시카보닐아미노)-3-[4-(5-브로모펜틸옥시)-페닐]프로피온산;2-S-(N-벤질옥시카보닐아미노)-3-[4-(4-피페라진-1-일)펜틸옥시페닐]프로피온산;2-S-(N-밴질옥시카보닐아미노)-3-[4-(6-아미노헥실옥시-페닐]프로피온산 하이드로클로라이드;2-S-(N-밴질옥시카보닐아미노)-3-[4-(7-아미노헥실옥시-페닐]프로피온산 하이드로클로라이드; 2-S-(N-벤질옥시카보닐아미노)-3-[4-(8-아미노옥틸옥시-페닐)프로피온산;2-S-(N-벤질옥시카보닐아미노)-3-[4-(5-아미노헥실옥시-페닐]프로피온산 하이드로클로라이드; 2-S-(N-벤질옥시카보닐아미노)-3-[4-(4-피페리디닐-부틸옥시)페닐]프로피온산 ; 2-S-(페닐카보닐아미노-3-[4-(6-아미노헬실옥시)페닐]-프로피온산 하이드로클로클로라이드; 2-S-(페닐아세틸아미노)-3-[4-6-아미노헥실옥시)페닐]프로피온산; 2-S-(2-카복시-3-페닐프로리오닐아미노)-3-[4-(6-아미노헥실옥시)페닐]프로피온산; 2-S-(헥사노닐아미노)-3-[4-(6-아미노헥실옥시)페닐]프로피온산 하이드로클로라이드;2-S-(나프타노일아미노)-3-[4-(6-아미노헥실옥시)페닐]프로피온산; 2-S-(부타노일아미노)-3-[4-(6-아미노헥실옥시)페닐]프로피온산; 2-S-(헵타노일아미노)-3-[4-(6-아미노헥실옥시)페닐]프로피온산 하이드로 클로라이드; 2-(S)-(5-페닐펜타노일아미노)-3-[6-t-부틸옥시카보닐아미노헥실옥시)페닐]프로피온산; 2-S-(5-페닐펜타노일아미노)-3-[4-(6-아미노헥실옥시)페닐]프로피온산 하이드로클로라이드; 2-S-(3-카복시프로파노일)아미노-3-[4-(6-아미노헥실옥시)페닐]프로피온산 하이드로클로라이드; 2-S-(아세틸아미노)-3-[4-(6-아미노헥실옥시)페닐]프로피온산 하이드로클로라이드; 2-S-(N-벤질옥시카보닐아미노)-3[4-(4-피페리디닐)-부트-2-에닐옥시페닐]프로피온산; 2-S-(N-t-벤질옥시카보닐아미노)-3-[4-(4-하이드록시부트-1-이닐)페닐]프로피온산; 2-S-(N-t-부틸옥시카보닐아미노)-3-[4-(4-하이드록시부틸)페닐]프로피온산; 2-S-(N-t-부틸옥시카보닐아미노)-3-[4-(4-t-부틸아미노부틸)페닐]프로피온산; 2-S-(펜타노일아미노)-3-[4-(4-피페리딘-4-일부틸옥시)-페닐]프로피온산 하이드로클로라이드; 2-S-(헥사노일아미노)-3-[4-(4-피페리딘-4-일부틸옥시)-페닐]프로피온산 ; 2-S-(5-아미노펜타노일)아미노-3-[4-(6-아미노헥실옥시)-페닐]프로피온산 하이드로클로라이드; 메틸 2-S-(4-카보메톡시부타노일)아미노-3-[4-(N-t-부틸옥시-카보닐아미오헥실옥시)페닐]프로피온산; 2-S-(4-카복시부타노일아미노)-3-[4-(6-아미노헥실옥시)-페닐]프로피온산; 및 2-S-(3-카복시프로파노일)아미노)-3-[4-(6-아미노헥실옥시)페닐]프로피온산 하이드로클로라이드 중에서 선택된 화합물.
  6. 포유동물에게 제1항에 다른 화합물을 약리학적 유효량으로 투여하는 단계를 포함함을 특징으로 하여, 포유동물에서 피브리노겐이 이의 수용체 부위에서 작용함을 차단하는 방법.
  7. 포유동물에게 제1항에 다른 화합물을 약리학적 유효량으로 투여하는 단계를 포함함을 특징으로 하여, 이를 필요로 하는 포유동물에서 혈전 및 색전형성을 예방하는 방법.
  8. 포유동물에게 제1항에 다른 화합물을 약리학적 유효량으로 투여하는 단계를 포함함을 특징으로 하여, 이를 필요로 하는 포유동물에서 혈전 및 색전형성을 치료하는 방법.
  9. 포유동물에게 제1항에 다른 화합물을 약리학적 유효량으로 투여하는 단계를 포함함을 특징으로 하여, 이를 필요로 하는 포유동물에서 혈소판의 응집을 억제시키는 방법.
  10. 제7항에 있어서, 상기 화합물을 항응고제와 공동 투여하는 방법.
  11. 제8항에 있어서, 상기 화합물을 항응고제와 공동 투여하는 방법.
  12. 제9항에 있어서, 상기 화합물을 항응고제와 공동 투여하는 방법.
  13. 제7항에 있어서, 상기 화합물을 혈전붕괴제와 공동 투여하는 방법.
  14. 제8항에 있어서, 상기 화합물을 혈전붕괴제와 공동 투여하는 방법.
  15. 제9항에 있어서, 상기 화합물을 혈전붕괴제와 공동 투여하는 방법.
  16. 제7항에 있어서, 상기 화합물을 혈소판 항응집제와 공동 투여하는 방법.
  17. 제8항에 있어서, 상기 화합물을 혈소판 항응집제와 공동 투여하는 방법
  18. 제9항에 있어서, 상기 화합물을 혈소판 항응집제와 공동 투여하는 방법
  19. 제7항에 다른 화합물 및 약제학적으로 허용가능한 담체를 함유함을 특징으로 하는 약제학적 조성물.
  20. 제1항에 따른 화합물, 약제학적으로 허용가능한 담체 및 혈전붕괴제, 혈소판 항응집제 및 항응고제로 구성된 그룹으로부터 선택된 화합물을 함유함을 특징으로 하는 약제학적 조성물.
  21. 제20항에 있어서, 상기 약제학적으로 허용가능한 담체가 서방형 약제학적 제형으로 구성된 조성물.
  22. 제1항에 따른 화합물 및 약제학적으로 허용가능한 담체를 함유함을 특징으로 하는, 포유동물에서 혈소판에 피브리노겐이 결합되는 것을 억제하기 위한 조성물.
  23. 제1항에 따른 화합물 및 약제학적으로 허용가능한 담체를 함유함을 특징으로 하는, 포유동물에서 혈소판 응집 억제용 조성물.
  24. 혈전붕괴제와 혼합된 제1항에 따른 화합물 및 약제학적으로 허용가능한 담체를 특징으로 하는 포유동물에서의 혈소판응집 억제용 조성물.
  25. 항응고제와 혼합된 제1항에 따른 화합물 및 약제학적으로 허용가능한 담체를 특징으로 하는 포유동물에서의 혈전 또는 색전 형성 예방용 조성물.
  26. 제1항에 따른 화합물 및 약제학적으로 허용가능한 담체를 함유함을 특징으로 하는 포유동물에서의 혈전 또는 색전 형성 예방용 조성물.
  27. 혈전붕괴제와 혼합된 제1항에 따른 화합물 및 약제학적으로 허용가능한 담체를 함유함을 특징으로 하는 포유동물에서의 혈전 또는 색전 형성 치료용 조성물.
  28. 항응고제와 혼합된 제1항에 따른 화합물 및 약제학적으로 허용가능한 담체를 함유함을 특징으로 하는 포유동물에서의 혈전 또는 색전 형성 치료용 조성물.
  29. 제1항에 따른 화합물 및 약제학적으로 허용가능한 담체를 함유함을 특징으로 하는 포유동물에서의 혈전 또는 색전 형성 치료용 조성물.
  30. 혈전붕괴제와 혼합된 제1항에 따른 화합물 및 약제학적으로 허용가능한 담체를 함유함을 특징으로 하는 포유동물에서의 혈전 또는 색전 형성 치료용 조성물.
  31. 항응고제와 혼합된 제1항에 따른 화합물 및 약제학적으로 허용가능한 담체를 함유함을 특징으로 하는 포유동물에서의 혈전 또는 색전 형성 치료용 조성물.
  32. 항혈소판제와 혼합된 제1항에 따른 화합물 및 약제학적으로 허용가능한 담체를 함유함을 특징으로 하는, 포유동물에서의 혈전 또는 색전 형성 치료용 조성물.
  33. 제20항에 따른 조성물을 포유동물에게 투여함을 특징으로 하여, 포유동물의 혈소판응집을 억제시키는 방법.
  34. 제21항에 따른 조성물을 포유동물에게 투여함을 특징으로 하여, 포유동물의 혈전, 색전형성을 예방하거나 치료하는 방법.
  35. 포유동물에서 피브리노겐이 혈소판과 결합하는 것을 억제시키고, 혈소판 응집을 억제시키며, 혈전 또는 색전 형성을 치료하거나 예방하는데 사용하기 위한 제1항에 따른 화합물.
  36. 포유동물에서 피브리노겐이 혈소판과 결합하는 것을 억제시키고, 혈소판 응집을 억제시키며, 혈전 또는 색전 형성을 치료하거나 예방하는데 사용하기 위한 제5항에 따른 화합물.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019910016837A 1990-09-27 1991-09-26 피브리노겐 수용체 길항제 KR920006298A (ko)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US58929990A 1990-09-27 1990-09-27
US07/589,299 1990-09-27
US75064591A 1991-08-30 1991-08-30
US07/750,645 1991-08-30

Publications (1)

Publication Number Publication Date
KR920006298A true KR920006298A (ko) 1992-04-27

Family

ID=27080499

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1019910016837A KR920006298A (ko) 1990-09-27 1991-09-26 피브리노겐 수용체 길항제

Country Status (16)

Country Link
US (1) US5294616A (ko)
EP (1) EP0478328B1 (ko)
JP (1) JPH0819066B2 (ko)
KR (1) KR920006298A (ko)
AT (1) ATE132850T1 (ko)
AU (1) AU653360B2 (ko)
CA (1) CA2052069A1 (ko)
DE (1) DE69116285T2 (ko)
DK (1) DK0478328T3 (ko)
ES (1) ES2083534T3 (ko)
FI (1) FI914535A (ko)
GR (1) GR3018635T3 (ko)
IE (1) IE68955B1 (ko)
IL (1) IL99537A (ko)
NO (1) NO177703C (ko)
PT (1) PT99097B (ko)

Families Citing this family (107)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB8919504D0 (en) * 1989-08-29 1989-10-11 Leo Pharm Prod Ltd Chemical compounds
KR930703024A (ko) * 1991-02-08 1993-11-29 리챠드 티. 딘 영상용 테크네튬-99m표지폴리펩티드
US6019958A (en) * 1991-02-08 2000-02-01 Diatide, Inc. Technetium-99m labeled peptides for imaging inflammation
US5736122A (en) * 1991-02-08 1998-04-07 Diatide, Inc. Technetium-99m labeled peptides for thrombus imaging
US6107459A (en) * 1991-02-08 2000-08-22 Diatide, Inc. Technetium-99m labeled peptides for diagnostic imaging
US5645815A (en) 1991-02-08 1997-07-08 Diatide, Inc. Radiolabled compounds for thrombus imaging
US5830856A (en) * 1991-02-08 1998-11-03 Diatide, Inc. Radiolabeled compounds for thrombus imaging
US5561220A (en) * 1991-02-08 1996-10-01 Diatech, Inc. Technetium-99m labeled peptides for imaging inflammation
HUT68769A (en) * 1991-05-07 1995-07-28 Merck & Co Inc FIBRINOGéN RECEPTOR ANTAGONIST COMPOUNDS AND PHARMACEUTICAL COMPOSITIONS COMPRISING THEM AS EFFECTIVE SUBSTANCE
US5321034A (en) * 1991-05-07 1994-06-14 Merck & Co., Inc. Fibrinogen receptor antagonists
PT100631B (pt) * 1991-06-28 1999-06-30 Smithkline Beecham Corp Antagonistas biciclicos de fibrinogenio, seu uso e composicoes farmaceuticas que os contem
US5939412A (en) * 1992-06-26 1999-08-17 Smithkline Beecham Corporation Bicyclic fibrinogen antagonists
US5204350A (en) * 1991-08-09 1993-04-20 Merck & Co., Inc. Method of inhibiting osteoclast-mediated bone resorption by administration of n-heterocyclicalkyl-substituted phenyl derivatives
US5217994A (en) * 1991-08-09 1993-06-08 Merck & Co., Inc. Method of inhibiting osteoclast-mediated bone resorption by administration of aminoalkyl-substituted phenyl derivatives
US5635477A (en) * 1991-09-30 1997-06-03 The Dupont Merck Pharmaceutical Company Cyclic compounds useful as inhibitors of platelet glycoprotein IIB/IIIA
US5206373A (en) * 1992-02-28 1993-04-27 Merck & Co., Inc. Process for preparing fibrinogen receptor antagonists
US5968476A (en) * 1992-05-21 1999-10-19 Diatide, Inc. Technetium-99m labeled peptides for thrombus imaging
AU4540693A (en) * 1992-06-25 1994-01-24 G.D. Searle & Co. Phenyl amidine alkanoic acids and lactones useful as platelet aggregation inhibitors
CA2144762A1 (en) * 1992-10-14 1994-04-28 George D. Hartman Fibrinogen receptor antagonists
US5340798A (en) * 1992-10-14 1994-08-23 Merck & Co., Inc. Fibrinogen receptor antagonists
EP0664792B1 (en) * 1992-10-14 2000-01-05 Merck & Co. Inc. Fibrinogen receptor antagonists
US5358956A (en) * 1992-10-14 1994-10-25 Merck & Co., Inc. Fibrinogen receptor antagonists
US5648368A (en) * 1992-12-01 1997-07-15 Merck & Co., Inc. Fibrinogen receptor antagonists
DE4302485A1 (de) * 1993-01-29 1994-08-04 Merck Patent Gmbh Piperazinderivate
US5409939A (en) * 1993-02-12 1995-04-25 G. D. Searle & Co. Phenyl amidine thio derivatives useful as platelet aggregation inhibitors
US5652242A (en) * 1993-03-29 1997-07-29 Zeneca Limited Heterocyclic derivatives
CA2156070A1 (en) * 1993-03-29 1994-10-13 Michael Garth Wayne Heterocyclic derivatives as platelet aggregation inhibitors
US5750754A (en) * 1993-03-29 1998-05-12 Zeneca Limited Heterocyclic compounds
US5753659A (en) * 1993-03-29 1998-05-19 Zeneca Limited Heterocyclic compouds
ZW4194A1 (en) * 1993-03-29 1994-12-21 Zeneca Ltd Heterocyclic compounds
US5750088A (en) 1993-03-30 1998-05-12 The Dupont Merck Pharmaceutical Company Stable hydrazones linked to a peptide moiety as reagents for the preparation of radiopharmaceuticals
CA2363780C (en) * 1993-04-08 2003-01-07 Diatide, Inc. Radiolabeled compounds for thrombus imaging
US5334596A (en) * 1993-05-11 1994-08-02 Merck & Co., Inc. Fibrinogen receptor antagonists
US5612355A (en) * 1993-06-23 1997-03-18 G. D. Searle & Co. Phenyl amidine lactones useful as platelet aggregation inhibitors
GB9313285D0 (en) * 1993-06-28 1993-08-11 Zeneca Ltd Acid derivatives
US5463011A (en) * 1993-06-28 1995-10-31 Zeneca Limited Acid derivatives
GB9313268D0 (en) * 1993-06-28 1993-08-11 Zeneca Ltd Chemical compounds
US6448269B1 (en) 1993-07-22 2002-09-10 Eli Lilly And Company Glycoprotein IIb/IIIa antagonists
US6137002A (en) * 1993-07-22 2000-10-24 Eli Lilly And Company Glycoprotein IIb/IIIa antagonists
IL110172A (en) * 1993-07-22 2001-10-31 Lilly Co Eli Bicycle compounds and pharmaceuticals containing them
US5731324A (en) * 1993-07-22 1998-03-24 Eli Lilly And Company Glycoprotein IIb/IIIa antagonists
US5397791A (en) * 1993-08-09 1995-03-14 Merck & Co., Inc. Fibrinogen receptor antagonists
DK0730589T3 (da) * 1993-11-24 1999-02-01 Du Pont Pharm Co Isoxazolinforbindelser, der er nyttige som fibrinogenreceptorantagonister
US5849736A (en) * 1993-11-24 1998-12-15 The Dupont Merck Pharmaceutical Company Isoxazoline and isoxazole fibrinogen receptor antagonists
US5523302A (en) * 1993-11-24 1996-06-04 The Du Pont Merck Pharmaceutical Company Aromatic compounds containing basic and acidic termini useful as fibrinogen receptor antagonists
EP0730590B1 (en) * 1993-11-24 2001-01-17 Dupont Pharmaceuticals Company isoxazoline and isoxazole fibrinogen receptor antagonists
US5446056A (en) * 1993-11-24 1995-08-29 The Du Pont Merck Pharmaceutical Company Isoxazoline compounds useful as fibrinogen receptor antagonists
US5563158A (en) * 1993-12-28 1996-10-08 The Dupont Merck Pharmaceutical Company Aromatic compounds containing basic and acidic termini useful as fibrinogen receptor antagonists
MA23420A1 (fr) * 1994-01-07 1995-10-01 Smithkline Beecham Corp Antagonistes bicycliques de fibrinogene.
US5821241A (en) * 1994-02-22 1998-10-13 Merck & Co., Inc. Fibrinogen receptor antagonists
JPH10501222A (ja) * 1994-05-27 1998-02-03 メルク エンド カンパニー インコーポレーテッド 破骨細胞仲介骨吸収を抑制するための化合物
US6458784B1 (en) 1994-06-29 2002-10-01 Smithkline Beecham Corporation Vitronectin receptor antagonists
US5451578A (en) * 1994-08-12 1995-09-19 Merck & Co., Inc. Fibrinogen receptor antagonists
US5525617A (en) * 1994-08-24 1996-06-11 Merck & Co., Inc. Fibrinogen receptor antagonists
US5494921A (en) * 1994-09-16 1996-02-27 Merck & Co., Inc. Fibrinogen receptor antagonists
US5719144A (en) * 1995-02-22 1998-02-17 Merck & Co., Inc. Fibrinogen receptor antagonists
ZA963391B (en) * 1995-05-24 1997-10-29 Du Pont Merck Pharma Isoxazoline fibrinogen receptor antagonists.
US5977101A (en) * 1995-06-29 1999-11-02 Smithkline Beecham Corporation Benzimidazoles/Imidazoles Linked to a Fibrinogen Receptor Antagonist Template Having Vitronectin Receptor Antagonist Activity
US6100423A (en) * 1995-08-30 2000-08-08 G. D. Searle & Co. Amino benzenepropanoic acid compounds and derivatives thereof
CA2230209A1 (en) 1995-08-30 1997-03-06 G.D. Searle & Co. Meta-guanidine, urea, thiourea or azacyclic amino benzoic acid derivatives as integrin antagonists
WO1997014417A1 (en) * 1995-10-19 1997-04-24 Merck & Co., Inc. Fibrinogen receptor antagonists
US5789421A (en) * 1995-10-26 1998-08-04 Merck & Co., Inc. Fibrinogen receptor antagonist
DE19548709A1 (de) * 1995-12-23 1997-07-03 Merck Patent Gmbh Tyrosinderivate
US5952306A (en) * 1996-01-16 1999-09-14 Merck & Co., Inc. Integrin receptor antagonists
JP2000505471A (ja) * 1996-02-28 2000-05-09 メルク エンド カンパニー インコーポレーテッド フィブリノーゲン受容体拮抗物質
US5780480A (en) * 1996-02-28 1998-07-14 Merck & Co., Inc. Fibrinogen receptor antagonists
ATE219764T1 (de) * 1996-03-29 2002-07-15 Searle & Co Zimtsäurederivate und deren verwendung als integrin-antagonisten
PT891325E (pt) * 1996-03-29 2002-07-31 Searle & Co Derivados do acido fenilpropanoico para-substituido como antagonistas de integrina
DE69706407T2 (de) * 1996-03-29 2002-05-29 Searle & Co META-SUBSTITUIERTE PHENYLENDERIVATE UND IHRE VERWENDUNG ALS ALPHAvBETA3 INTERGRIN-ANTAGONISTEN ODER INHIBITOREN
DE69705300T2 (de) * 1996-03-29 2002-05-02 Searle & Co Cyclopropylalkansäurederivate
EP0889876B1 (en) 1996-03-29 2001-07-25 G.D. SEARLE & CO. Meta-substituted phenylene sulphonamide derivatives
US5889023A (en) * 1996-05-10 1999-03-30 Merck & Co., Inc. Fibrinogen receptor antagonist
JP2000515133A (ja) 1996-07-01 2000-11-14 イーライ・リリー・アンド・カンパニー 血糖降下性および脂質低下性の化合物
US6004955A (en) * 1996-08-15 1999-12-21 Dupont Pharmaceuticals Company Cyclic carbamates and isoxazolidines as IIb/IIIa antagonists
GB2318053A (en) * 1996-10-08 1998-04-15 Merck & Co Inc Angioplasty procedure using nonionic contrast media
US5981584A (en) * 1997-02-06 1999-11-09 Merck & Co., Inc. Fibrinogen receptor antagonist prodrugs
US6294549B1 (en) 1997-07-23 2001-09-25 Merck & Co., Inc. Method for eliciting an αvβ5 or dual αvβ3/αvβ5 antagonizing effect
PL339660A1 (en) 1997-10-02 2001-01-02 Sankyo Co Derivatives of amidocarboxylic acids
IL136267A0 (en) * 1997-11-26 2001-05-20 Du Pont Pharm Co 1,3,4-THIADIZOLES AND 1,3,4-OXADIAZOLES AS αVβ3 ANTAGONISTS
JPH11279040A (ja) 1998-03-27 1999-10-12 Kao Corp 皮膚外用剤
JP2003504301A (ja) 1998-04-01 2003-02-04 ブリストル−マイヤーズ スクイブ ファーマ カンパニー インテグリンアンタゴニスト
EP1091945A1 (en) 1998-06-29 2001-04-18 Du Pont Pharmaceuticals Company Cyclic carbamates and isoxazolidines as iib/iiia antagonists
US6204282B1 (en) 1998-11-30 2001-03-20 Schering Corporation Benzimidazole compounds that are vitronectin receptor antagonists
US6808698B1 (en) 1999-03-26 2004-10-26 Bristol-Myers Squibb Pharma Company Method for localization of blood clots
US6348504B1 (en) 1999-03-30 2002-02-19 Richard E. Olson Oxime ethers as IIb/IIa antagonists
US6375948B1 (en) * 1999-07-12 2002-04-23 Kao Corporation Treating method for suppressing hair growth
US6254852B1 (en) 1999-07-16 2001-07-03 Dupont Pharmaceuticals Company Porous inorganic targeted ultrasound contrast agents
US6685914B1 (en) 1999-09-13 2004-02-03 Bristol-Myers Squibb Pharma Company Macrocyclic chelants for metallopharmaceuticals
US6518244B2 (en) 2000-03-09 2003-02-11 Intimax Corporation Combinations of heparin cofactor II agonist and platelet IIb/IIIa antagonist, and uses thereof
GB0010955D0 (en) 2000-05-05 2000-06-28 Novartis Ag Organic compounds
PE20020665A1 (es) 2000-06-15 2002-08-14 Pharmacia Corp ACIDO CICLOALQUIL FENIL ALCANOICO COMO ANTAGONISTA DE INTEGRINAS OVß3
US6531494B1 (en) 2001-08-29 2003-03-11 Pharmacia Corporation Gem-substituted αvβ3 antagonists
AR039156A1 (es) 2002-03-28 2005-02-09 Novartis Ag Amidas del acido piperidinilamino sulfamico o piperazinil sulfamico y su uso para la manufactura de un medicamento en enfermedades mediadas por la accion de la sulfatasa esteroide
US7317104B2 (en) 2003-06-13 2008-01-08 Bristol-Myers Squibb Pharma Company Chelants and macrocyclic metal complex radiopharmaceuticals thereof
US7319149B2 (en) 2003-06-13 2008-01-15 Bristol-Myers Squibb Pharma Company Chelants and macrocyclic metal complex radiopharmaceuticals thereof
CA3005835C (en) * 2004-12-22 2023-01-31 Ambrx, Inc. Compositions containing, methods involving, and uses of non-natural amino acids and polypeptides
JP2009516730A (ja) * 2005-11-23 2009-04-23 アストラゼネカ アクチボラグ Ｌ−アラニン誘導体
EP2049490A1 (en) * 2006-06-09 2009-04-22 Astra Zeneca AB N-(benzoyl)-o- [2- (pyridin- 2 -ylamino) ethyl]-l-tyrosine derivatives and related compounds as a5b1 antagonists for the treatment of solid tumors
US20090062267A1 (en) * 2007-01-29 2009-03-05 Astrazeneca Ab L-ALANINE DERIVATIVES AS a5beta1 ANTAGONISTS
WO2008125811A1 (en) * 2007-04-11 2008-10-23 Astrazeneca Ab N-[HETEROARYLCARBONYL]-S-THIENYL-L-ALANINE DERIVATIVES AS α5β1 ANTAGONISTS
JP6630671B2 (ja) 2013-12-18 2020-01-15 グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ Ｎｒｆ２レギュレーター
CN103708392A (zh) * 2013-12-31 2014-04-09 中国重型机械研究院股份公司 一种可实现全自动控制的钢卷翻卷机
CN104693096A (zh) * 2015-02-13 2015-06-10 佛山市赛维斯医药科技有限公司 含双酰肼和萘基结构的化合物、制备方法及其用途
CN104693102A (zh) * 2015-02-13 2015-06-10 佛山市赛维斯医药科技有限公司 一种双酰肼类化合物、其制备方法及其用途
PL3307739T3 (pl) 2015-06-15 2021-05-31 Glaxosmithkline Intellectual Property Development Limited Regulatory nrf2
JP6786527B2 (ja) 2015-06-15 2020-11-18 グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ Ｎｒｆ２レギュレーター
US10364256B2 (en) 2015-10-06 2019-07-30 Glaxosmithkline Intellectual Property Development Limited Biaryl pyrazoles as NRF2 regulators

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1062206B (it) * 1974-02-01 1983-09-20 Rotta Research Lab S P A A S Derivati della tirosina attivi sulla muscolatura liscia
DE2549999A1 (de) * 1975-11-07 1977-05-12 Boehringer Mannheim Gmbh Piperidin-derivate und verfahren zu ihrer herstellung
US4064125A (en) * 1976-10-29 1977-12-20 E. R. Squibb And Sons, Inc. Substituted amides having antiinflammatory activity
EP0021592B1 (en) * 1979-05-23 1983-09-28 BEECHAM - WUELFING GmbH & Co. KG Phenylsulphonamide derivatives, a process for their preparation and their use as medicines
US4479942A (en) * 1981-08-10 1984-10-30 Fujisawa Pharmaceutical Co., Ltd. Tetrahydrofurnancarboxylic acid derivatives, processes for preparation thereof and pharmaceutical compositions thereof
KR880007441A (ko) * 1986-12-11 1988-08-27 알렌 제이.스피겔 스피로-치환된 글루타르아미드 이뇨제
US5084466A (en) * 1989-01-31 1992-01-28 Hoffmann-La Roche Inc. Novel carboxamide pyridine compounds which have useful pharmaceutical utility
CA2008116C (en) * 1989-02-23 2001-11-20 Thomas Weller Glycine derivatives
DE4009506A1 (de) * 1990-03-24 1991-09-26 Hoechst Ag Hydantoinderivate

Also Published As

Publication number Publication date
EP0478328B1 (en) 1996-01-10
JPH05155828A (ja) 1993-06-22
ATE132850T1 (de) 1996-01-15
IL99537A (en) 1995-11-27
FI914535A0 (fi) 1991-09-26
US5294616A (en) 1994-03-15
FI914535A (fi) 1992-03-28
PT99097A (pt) 1992-08-31
NO177703B (no) 1995-07-31
EP0478328A1 (en) 1992-04-01
IE68955B1 (en) 1996-07-24
NO913787L (no) 1992-03-30
AU8478891A (en) 1992-04-02
DE69116285D1 (de) 1996-02-22
GR3018635T3 (en) 1996-04-30
DE69116285T2 (de) 1996-10-17
PT99097B (pt) 1999-02-26
IE913382A1 (en) 1992-04-08
AU653360B2 (en) 1994-09-29
DK0478328T3 (da) 1996-02-05
NO177703C (no) 1995-11-08
NO913787D0 (no) 1991-09-26
ES2083534T3 (es) 1996-04-16
JPH0819066B2 (ja) 1996-02-28
CA2052069A1 (en) 1992-03-28
IL99537A0 (en) 1992-08-18

Similar Documents

Publication Publication Date Title
KR920006298A (ko) 피브리노겐 수용체 길항제
US11793798B2 (en) Pharmaceutical formulations comprising a pyridylaminoacetic acid compound
KR950032037A (ko) 신규의 델타-아미노-감마-히드록시-오메가-아릴-알칸산 아미드
KR920006313A (ko) 설폰아미드 피브리노겐 수용체 길항제
KR930009993A (ko) 혈전증 치료제
RU99105567A (ru) Производные пропионовой кислоты и их использование
TNSN90003A1 (fr) Derives de 2-aminopyrimidinones utiles notamment comme antagonistes des neurotransmetteurs et procede pour leur preparation
WO2001090070A3 (en) Caspase inhibitors and uses thereof
SK10095A3 (en) Injection and injection kit containing omeprazole and its analogs
PL1683524T3 (pl) Stała dyspersja lub preparat farmaceutyczny stałej dyspersji pochodnej fenyloalaniny
KR960022449A (ko) 방향족 치환된 ω-아미노-알칸산 아미드 및 알칸산 디아미드
CA2475619A1 (en) Piperidine derivatives
MXPA06012655A (es) Preparaciones topicas que contienen ambroxol.
KR20170129170A (ko) 서방성 의약 조성물
RU96109467A (ru) Новые соединения, обладающие способностью ингибировать агрегацию тромбоцитов
US5066664A (en) 2-(hydroxy-2-alkylphenylamino)-oxazolines and thiazolines as anti-glaucoma and vasoconstrictive agents
KR100215533B1 (ko) 아르기닌 아미드 함유 의약 조성물
CA2237898A1 (en) Combination therapy for treating glaucoma
KR930002319A (ko) Aids 치료에 유용한 hiv 프로테아제의 억제제
US4705781A (en) Method of treating cerebral ischemia using 4-(phosphono substituted lower alkyl or lower alkenyl)piperazine-2-carboxylic acids and salts, esters and amides thereof
TWI794140B (zh) 含有吡啶基胺基乙酸化合物之預防及/或治療劑
US11666563B2 (en) Pharmaceutical preparation containing pyridyl aminoacetic acid compound
RU98106104A (ru) Производные пиримидина
KR880001593A (ko) 4-(아로일아미노)피페리딘부탄아미드 유도체
US7320982B2 (en) Use of 4-substituted tetrahydropyridines for the manufacture of medicaments acting upon TGF-β 1

Legal Events

Date Code Title Description
WITN Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid