KR950032285A - 히루딘 유도체 및 이의 제조방법 - Google Patents

히루딘 유도체 및 이의 제조방법 Download PDF

Info

Publication number
KR950032285A
KR950032285A KR1019950002200A KR19950002200A KR950032285A KR 950032285 A KR950032285 A KR 950032285A KR 1019950002200 A KR1019950002200 A KR 1019950002200A KR 19950002200 A KR19950002200 A KR 19950002200A KR 950032285 A KR950032285 A KR 950032285A
Authority
KR
South Korea
Prior art keywords
phenyl
hydrogen atom
amino acid
compound
alkyl
Prior art date
Application number
KR1019950002200A
Other languages
English (en)
Other versions
KR100351389B1 (ko
Inventor
오베르마이어 라이너
루드비히 위르겐
트리피에 도미니크
로포트 막스
Original Assignee
짜우너, 루츠
훽스트 아크티엔게젤샤프트
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 짜우너, 루츠, 훽스트 아크티엔게젤샤프트 filed Critical 짜우너, 루츠
Publication of KR950032285A publication Critical patent/KR950032285A/ko
Application granted granted Critical
Publication of KR100351389B1 publication Critical patent/KR100351389B1/ko

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K14/00—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
    • C07K14/81—Protease inhibitors
    • C07K14/815—Protease inhibitors from leeches, e.g. hirudin, eglin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/56—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
    • A61K47/59—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
    • A61K47/60—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Genetics & Genomics (AREA)
  • Molecular Biology (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Engineering & Computer Science (AREA)
  • Biophysics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Biochemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Gastroenterology & Hepatology (AREA)
  • Epidemiology (AREA)
  • Diabetes (AREA)
  • Hematology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Abstract

히루딘 유도체는 분자의 일부를, 아미노 유도체를 사용하여 선택적 효소적 치환시켜 제조할 수 있다. 히루딘 유도체는 항응혈 효과를 갖는 약제를 제조하는데 적합하다.

Description

히루딘 유도체 및 이의 제조방법
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음

Claims (9)

  1. 하기 일반식(I) 또는 (II)의 화합물.
    A0-A1-A2-(히루딘 3-36)-(Y), (히루딘 37-65) (I)
    A0-A1-A2-(히루딘 3-63)-(Y) (II)
    상기식에서, A1은 아미노산 잔기이고, A2은 아미노산 잔기이며, A0은 아미노산 잔기 또는 수소원자이고, Y는 일반식 H2N-R-X (IIIa) 또는 A-R1-X(IIIb)의 아민 유도체이며, A는 a)아미노산 잔기 또는 b)2 내지 10개의 아미노산 잔기를 갖는 펩티드이고, R은 a)직쇄 또는 측쇄(C1-C10)알킬, b)1)페닐, 2)페닐, 2)인돌릴, 3)이미다졸릴 또는 4)하이드록실에 의해 1회 이상 치환된 페닐에 의해 서로 독립적으로 1회 이상 치환된 직쇄 또는 측쇄(C1-C10)알킬, c)페닐 또는 d)나프틸이며, R1은 a)수소원자, b)공유결합, c)글루코즈, 프럭토즈, 만노즈, 갈락토즈, 리보즈, 리볼로즈 또는 크실로즈와 같은 당, d)2 내지 10개의 당을 함유하는 폴리사카라이드즈 또는 e)-[O-(CH2)m]n-(여기서, m은 정수 2,3,4 또는 5이고 n은 정수 1 내지 100이다)이고, X는 a)수소원자, b)-RO2, c)-SR2, d)-NHR2, e)-COOR2또는 f)A[여기서, R2는 1)수소원자, 2)직쇄 또는 측쇄(C1-C10)알킬, 3)3.1 페닐, 3.2 인돌릴, 3.3 이미다졸릴 또는 3.4 하이드록실에 의해 1회 이상 치환된 페닐에 의해 1회 이상 치환된 직쇄 또는 측쇄(C1-C10)알킬, 4)페닐 또는 5)나프틸이다]이다.
  2. 제1항에 있어서, A가 2 내지 5개의 아미노산 잔기를 갖는 펩티드이고, R이 1)페닐, 2)인돌릴, 3)이미다졸릴 또는 4)4-하이드록시페닐에 의해 치환된 에틸이며, R1이 -[O-(CH2)m]n-(여기서, m은 숫자 2이고 n은 정수 20 내지 50이다)이고, X가 a)수소원자, b)-OR2, c)-NHR2, d)-COOR2[여기서, R2는 1)수소 원자, 2)(C1-C5)알킬 또는 3)페닐이다]인 일반식(I) 또는 (II)의 화합물.
  3. 제1항 또는 제2항에 있어서, A가 그룹 Thr 또는 Arg으로부터의 2 내지 5개의 아미노산 잔기를 갖는 펩티드이고, R1이 a)수소원자 또는 b)공유결합, c)글루코즈 또는 d)분자량이 100 내지 내지 3,000g/mal인 폴리에틸렌 글리콜이며, X가 a)수소원자 또는 b)-OR2(여기서, R2는 3급 부틸이다)인 일반식(I) 또는 (II)의 화합물.
  4. 제1항 내지 제3항 중 어느 한 항에 있어서, R1이 분자량 1,500g/mol의 폴리에틸렌 잔기인 일반식(I)또는 (II)의 화합물.
  5. 일반식(IIIa) 또는 (IIIb)의 아민 유도체를 프로테아제의 존재하에 히루딘과 반응시켜 제1항 내지 제4항에 청구된 화합물을 제조하는 방법.
  6. 제5항에 있어서, 키모트립신, 트립신, 또는 리실엔도펩티다제와 같은 트립신-유사 효소중에서 선택된 프로테아제를 사용하는 방법.
  7. 제1항 내지 제4항에 청구된 화합물을 함유하는 약제.
  8. 제1항 내지 제4항중에 청구된 일반식(I) 또는 (II)의 화합물의 향응혈 효과를 갖는 약제를 제조하기 위한 용도.
  9. 제7항에 청구된 약제의 특히 이온침투요법에 의한 경피 투여용 용도.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019950002200A 1994-02-10 1995-02-08 히루딘유도체및이의제조방법 KR100351389B1 (ko)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DEP4404168.3 1994-02-10
DE4404168A DE4404168A1 (de) 1994-02-10 1994-02-10 Hirudinderivate und Verfahren zu deren Herstellung

Publications (2)

Publication Number Publication Date
KR950032285A true KR950032285A (ko) 1995-12-20
KR100351389B1 KR100351389B1 (ko) 2002-12-16

Family

ID=6509914

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1019950002200A KR100351389B1 (ko) 1994-02-10 1995-02-08 히루딘유도체및이의제조방법

Country Status (7)

Country Link
US (1) US5674838A (ko)
EP (1) EP0667355A1 (ko)
JP (1) JPH07252299A (ko)
KR (1) KR100351389B1 (ko)
AU (1) AU697362B2 (ko)
CA (1) CA2142173A1 (ko)
DE (1) DE4404168A1 (ko)

Families Citing this family (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
IT1285405B1 (it) * 1995-06-06 1998-06-03 Alza Corp Modificazione di farmaci polipeptidici per accrescere il flusso per elettrotrasporto.
US5747453A (en) * 1995-06-06 1998-05-05 Alza Corporation Method for increasing the electrotransport flux of polypeptides
WO2006000081A1 (en) * 2004-06-23 2006-01-05 National Research Council Of Canada Polypeptide ligands containing linkers
DE602005023429D1 (de) 2004-10-19 2010-10-21 Lonza Ag Verfahren zur festphasen-peptidsynthese

Family Cites Families (23)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4179337A (en) * 1973-07-20 1979-12-18 Davis Frank F Non-immunogenic polypeptides
DE3101382A1 (de) * 1981-01-17 1982-09-02 Hoechst Ag, 6000 Frankfurt "verfahren zur herstellung von humanisulin oder dessen derivaten aus schweineinsulin oder dessen derivaten"
DE3342139A1 (de) * 1983-11-22 1985-05-30 Ciba-Geigy Ag, Basel Desulfatohirudine, verfahren zu ihrer herstellung und pharmazeutische mittel
CA1341417C (fr) * 1984-03-27 2003-01-21 Paul Tolstoshev Vecteurs d'expression de l'hirudine, cellules transformees et procede de preparation de l'hirudine
DE3438296A1 (de) * 1984-04-18 1985-11-07 Hoechst Ag, 6230 Frankfurt Neue polypeptide mit blutgerinnungshemmender wirkung, verfahren zu deren herstellung bzw. gewinnung, deren verwendung und diese enthaltende mittel
ATE64956T1 (de) * 1984-06-14 1991-07-15 Ciba Geigy Ag Verfahren zur herstellung von thrombininhibitoren.
DE3429430A1 (de) * 1984-08-10 1986-02-20 Hoechst Ag, 6230 Frankfurt Gentechnologisches verfahren zur herstellung von hirudin und mittel zur durchfuehrung dieses verfahrens
DE3445517C2 (de) * 1984-12-13 1993-11-18 Ciba Geigy Für ein Hirudin-ähnliches Protein codierende DNA-Sequenz und Verfahren zur Herstellung eines Hirudin-ähnlichen Proteins
DE3506992A1 (de) * 1985-02-27 1986-08-28 Plantorgan Werk Heinrich G.E. Christensen, KG, 2903 Bad Zwischenahn Modifizierte hirudine, verfahren zu deren herstellung und pharmazeutische mittel, die diese wirkstoffe enthalten
EP0324712B1 (de) * 1985-04-11 1993-04-07 Hoechst Aktiengesellschaft Hirudin-Derivat
DE3738541A1 (de) * 1987-11-13 1989-05-24 Hoechst Ag Verfahren zur isolierung und reinigung von hirudin
DE3689525D1 (de) * 1985-07-17 1994-02-24 Hoechst Ag Neue Polypeptide mit blutgerinnungshemmender Wirkung, Verfahren zu deren Herstellung bzw. Gewinnung, deren Verwendung und diese enthaltende Mittel.
DE3541856A1 (de) * 1985-11-27 1987-06-04 Hoechst Ag Eukaryotische fusionsproteine, ihre herstellung und verwendung sowie mittel zur durchfuehrung des verfahrens
US4847325A (en) * 1988-01-20 1989-07-11 Cetus Corporation Conjugation of polymer to colony stimulating factor-1
AU604925B2 (en) * 1988-02-23 1991-01-03 Schering Aktiengesellschaft A hirudin derivative
FR2628429B1 (fr) * 1988-03-08 1990-12-28 Transgene Sa Variants de l'hirudine, leurs utilisations et les procedes pour les obtenir
AU614121B2 (en) * 1988-05-04 1991-08-22 Novartis Ag Improvements in the production of polypeptides
DE3819079A1 (de) * 1988-06-04 1989-12-07 Hoechst Ag Hirudin-derivate mit verzoegerter wirkung
EP0502962B1 (de) * 1989-12-01 1996-03-13 BASF Aktiengesellschaft Hirudin-Muteine und deren Polyalkylenglykolkonjugate
US5118790A (en) * 1990-07-24 1992-06-02 Sri International Analogs of hirudin
US5458568A (en) * 1991-05-24 1995-10-17 Cortrak Medical, Inc. Porous balloon for selective dilatation and drug delivery
IT1250689B (it) * 1991-07-22 1995-04-21 Marco Gerna Analoghi dell'irudina e procedimento per la loro preparazione
FR2687681B1 (fr) * 1992-02-20 1995-10-13 Transgene Sa Conjugues polyethyleneglycol-hirudine, leur procede de preparation et leur emploi pour le traitement des thromboses.

Also Published As

Publication number Publication date
DE4404168A1 (de) 1995-08-17
JPH07252299A (ja) 1995-10-03
KR100351389B1 (ko) 2002-12-16
AU697362B2 (en) 1998-10-01
AU1163795A (en) 1995-08-17
US5674838A (en) 1997-10-07
EP0667355A1 (de) 1995-08-16
CA2142173A1 (en) 1995-08-11

Similar Documents

Publication Publication Date Title
DE60303961D1 (de) Modifizierte saccharide, deren konjugate sowie deren herstellung
Nishimura et al. Synthetic glycoconjugates. 2. n-Pentenyl glycosides as convenient mediators for the syntheses of new types of glycoprotein models
Murata et al. Preparation of oligosaccharide units library and its utilization
IE59734B1 (en) New oligosaccharides, immunogens and vaccines, and methods for preparing such oligosaccharides, immunogens and vaccines
CA2212856A1 (en) Benzopyran-containing compounds and method for their use
DK0751144T3 (da) Nye antracyclin-pro-drugs, fremgangsmåde til fremstilling deraf samt antitumorsammensætninger og et komponentkit indeholdende disse pro-drugs
DE3579751D1 (de) Gluco-oligosaccharid-gemisch und verfahren zu seiner herstellung.
ATE50774T1 (de) Neue fructosyltsansferase und verfahren zur herstellung von fructosyl-disacchariden, sowie eine neue halosaccharose.
EP1453888B1 (en) Saccharide residue-functional organopolycarbosiloxanes and method for the preparation thereof
KR950032285A (ko) 히루딘 유도체 및 이의 제조방법
Fernandez-Santana et al. Glycosides of Monoallyl Diethylene Glycol. A New type of Spacer group for Synthetic Oligosaccharides
Schray et al. Inactivation of muscle triose phosphate isomerase by D-and L-glycidol phosphate
Eberling et al. Chemoselective removal of protecting groups from O-glycosyl amino acid and peptide (methoxyethoxy) ethyl esters using lipases and papain
MY103552A (en) Saccharide derivatives
Michalski et al. Behavior of the 2-acetamido-2-deoxy-α-D-glucopyranosyl residue during sequential hydrazinolysis, N-reacetylation, reduction, and methylation of glycoasparagines
WO1999055718A3 (en) Solution phase biopolymer synthesis
Fujita et al. 2A, 2B-, 2A, 2C-, And 2A, 2D-bis-O-(p-tolylsulfonyl)-. BETA.-cyclodextrins.
EP0451267A4 (en) Process for preparing ganglioside g m1?
Reid et al. Pepsin-catalyzed hydrolysis of sulfite esters. II. Resolution of alkyl phenyl sulfites
FR2346368A1 (fr) Nouveaux derives de sucres amines et medicament les contenant
Fekete et al. Preparation of synthetic oligosaccharide-conjugates of poly-β-(1→ 6)-N-acetyl glucosamine
Ariosa-Alvarez et al. Synthesis of the Vibrio Cholerae O1 Ogawa and Inaba Terminal Disaccharides With Dioxolane-Type Spacers and their Coupling to Proteins1
GR74471B (ko)
WO1997022368A3 (de) Kovalente lipid-phosphonocarbonsäure-konjugate und ihre anwendung wie antivirale arzneimittel
Garegg et al. Synthesis of oligosaccharides corresponding to structures found in capsular polysaccharides of Cryptococcus neoformans—II

Legal Events

Date Code Title Description
A201 Request for examination
E701 Decision to grant or registration of patent right
GRNT Written decision to grant
LAPS Lapse due to unpaid annual fee