KR890000514A - 트립신형 프로테아제의 펩타이드 붕산 억제제 - Google Patents

트립신형 프로테아제의 펩타이드 붕산 억제제 Download PDF

Info

Publication number
KR890000514A
KR890000514A KR1019880006671A KR880006671A KR890000514A KR 890000514 A KR890000514 A KR 890000514A KR 1019880006671 A KR1019880006671 A KR 1019880006671A KR 880006671 A KR880006671 A KR 880006671A KR 890000514 A KR890000514 A KR 890000514A
Authority
KR
South Korea
Prior art keywords
mammal
compound
effective amount
inhibiting
physiologically acceptable
Prior art date
Application number
KR1019880006671A
Other languages
English (en)
Other versions
KR910003619B1 (ko
Inventor
애드리안 케트너 찰스
비카파 쉔비 아쇼쿠마르
Original Assignee
제임스 제이.플린
이.아이.듀퐁 드 네모아 앤드 캄파니
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 제이.플린, 이.아이.듀퐁 드 네모아 앤드 캄파니 filed Critical 제임스 제이.플린
Publication of KR890000514A publication Critical patent/KR890000514A/ko
Application granted granted Critical
Publication of KR910003619B1 publication Critical patent/KR910003619B1/ko

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
    • C07K5/10—Tetrapeptides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • 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
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F5/00—Compounds containing elements of Groups 3 or 13 of the Periodic Table
    • C07F5/02—Boron compounds
    • C07F5/025—Boronic and borinic acid compounds

Landscapes

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

Abstract

내용 없음

Description

트립신형 프로테아제의 펩타이드 붕산 억제제
본 내용은 요부공개 건이므로 전문내용을 수록하지 않았음
제 1 도는 본 발명의 두가지 억제제, H-(D)-Phe-Pro-보로 Arg-C10H16및 Boc-(D)Phe-Phe-보로 Arg-C10H16의 억제제 농도에 대한 상대적 응괴 시간을 플롯(plot)한 것이다.

Claims (45)

  1. 하기 일반식(Ⅰ)의 화합물 또는 이의 생리학적으로 허용되는 염.
    상기식에서, Y1또는 Y2는 독립적으로 -OH 또는 F이거나, 또는 함께는, 1 내지 약 20개의 탄소원자 및 임의로는, N,S 또는 O일수 있는 헤테로원자 하나를 함유하는 쇄 또는 환내의 적어도 두개의 연결원자에 의해 분리된 적어도 두개의 하이드록시 그룹을 갖는 디하이드록시 화합물로부터 유도된 부분을 형성하고 ; R2는 -(CH2)2-X, -CH(CH3)-(CH2)2-X, -CH2-CH(CH3), -CH2-X, -(CH2)2-CH(CH3)-X, 및-(CH2)2-CH(CH3)CH2-X[여기에서, X는 -NH2, -NH-C(NH)-NH2또는 -S-C(NH)-NH2이고, Z는 3 내지 5이다]로 구성된 그룹으로부터 선택되는 치환된 알킬이고 ; n,o,p 및 q는 독립적으로 1 또는 0이고 ; A1, A2및 A3는 독립적으로, Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, 및 Val으로 구성된 그룹으로부터 선택되는 L- 또는 D-배위인 아미노산이며 ; R1은 1 내지 약 20개의 아미노산을 함유하는 펩타이드, 1 내지 약 20개의 탄소원자를 함유하는 아실 또는 설포닐그룹, H 또는 N-말단보호 그룹이다.
  2. 제 1 항에 있어서, A1이 Lys, Phe, Pro, Ala, Leu, Gly, Glu, Val, Thr, Ile, Met, Tyr, Trp, Arg, Asp, Asn 및 Gln로 구성된 그룹으로부터 선택되는 L- 또는 D-배위의 아미노산인 화합물.
  3. 제 2 항에 있어서, A1이 Lys, Phe, Pro, Ala, Leu, Gly, Glu, Val 및 Thr로 구성된 그룹으로부터 선택되는 L- 또는 D-배위의 아미노산인 화합물.
  4. 제 1 항에 있어서, A2가 D-배위의 아미노산인 화합물.
  5. 제 4 항에 있어서, A2가 Phe인 화합물.
  6. 제 1 항에 있어서, A2가 Phe, Ala, Leu, Pro, Glu 및 Gly로 구성된 그룹으로부터 선택되는 L- 또는 D-배위의 아미노산인 화합물.
  7. 제 1 항에 있어서, R2가 일반식 -(CH2)z-X로 구성된 그룹으로부터 선택되는 치환된 알킬인 화합물.
  8. 제 7 항에 있어서, Z가 3 내지 4인 화합물.
  9. 제 7 항에 있어서, R2가 3-구아니디노-프로필, 3-아미노-프로필 및 4-아미노-부틸로 구성된 그룹으로부터 선택되는 화합물.
  10. 제 9 항에 있어서, R2가 3-구아니디노-프로필인 화합물.
  11. 제 1 항에 있어서, Ac-(D)Phe-Pro- 보로 Arg-OH인 화합물.
  12. 제 1 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 트립신형 세린 프로테아제를 억제하기 위한 조성물.
  13. 제 2 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 트립신형 세린 프로테아제를 억제하기 위한 조성물.
  14. 제11항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 트립신형 세린 프로테아제를 억제하기 위한 조성물.
  15. 제 1 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 트롬빈을 억제하기 위한 조성물.
  16. 제 2 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 트롬빈을 억제하기 위한 조성물.
  17. 제11항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 트롬빈을 억제하기 위한 조성물.
  18. 제 1 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 혈장 칼리크레인을 억제하기 위한 조성물.
  19. 제 2 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 혈장 칼리크레인을 억제하기 위한 조성물.
  20. 제 1 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 플라즈민을 억제하기 위한 조성물.
  21. 제 2 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 플라즈민을 억제하기 위한 조성물.
  22. 제 1 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 혈액응고를 치료하기 위한 조성물.
  23. 제 2 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 혈액응고를 치료하기 위한 조성물.
  24. 제11항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 혈액응고를 치료하기 위한 조성물.
  25. 제 1 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 염증을 치료하기 위한 조성물.
  26. 제 2 항의 화합물의 유효량 및 생리학적으로 허용되는 담체 또는 희석제를 함유함을 특징으로 하는, 포유류에서 염증을 치료하기 위한 조성물.
  27. 제 1 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 트립신형 세린 프로테아제를 억제하는 방법.
  28. 제 2 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 트립신형 세린 프로테아제를 억제하는 방법.
  29. 제11항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 트립신형 세린 프로테아제를 억제하는 방법.
  30. 제 1 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 트롬빈을 억제하는 방법.
  31. 제 2 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 트롬빈을 억제하는 방법.
  32. 제11항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 트롬빈을 억제하는 방법.
  33. 제 1 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 혈장 칼리크레인을 억제하는 방법.
  34. 제 2 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 혈장 칼리크레인을 억제하는 방법.
  35. 제 1 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 플라즈민을 억제하는 방법.
  36. 제 2 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 플라즈민을 억제하는 방법.
  37. 제 1 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 혈액응고를 치료하는 방법.
  38. 제 2 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 혈액응고를 치료하는 방법.
  39. 제11항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 혈액응고를 치료하는 방법.
  40. 제 1 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 염증을 치료하는 방법.
  41. 제 2 항의 화합물의 유효량을 포유류에 투여함을 특징으로 하여, 포유류에서 염증을 치료하는 방법.
  42. 하기 일반식(Ⅱ)의 화합물.
    상기식에서, Y3는 1 내지 약 20개의 탄소원자를 함유하는 쇄 또는 환내의 적어도 두개의 연결원자에 의해 분리된 적어도 두개의 하이드록시그룹을 갖는 디하이드록시 화합물로부터 유도된 부분이고 ; R3는 -(CH2)Z-W1, -CH(CH3)-(CH2)2-W1, -CH2-CH(CH3)-CH2-W1, -(CH2)2-CH(CH3)-W1및 -(CH2)2-CH(CH3)2-W1으로 구성된 그룹으로부터 선택되는 치환된 알킬이고 ; W 및 W1는 독립적으로 Cl 또는 Br이고 ; Z는 3 내지 5이다.
  43. 제42항에 있어서, R3가 -(CH2)Z-W1이고, Z가 3 내지 4인 화합물.
  44. 하기 일반식(Ⅲ)의 화합물.
    상기식에서, Y3는 1 내지 약 20개의 탄소원자를 함유하는 쇄 또는 환내의 적어도 두개의 연결원자에 의해 분리된 적어도 두개의 하이드록시그룹을 갖는 디하이드록시 화합물로부터 유도된 부분이고 ; R4는 -(CH2)Z-W2, -CH(CH3)-(CH2)2-W2, -CH2-CH(CH3)-CH2-W2, -(CH2)2-CH(CH3)-W2및 -(CH2)2-CH(CH3)2-W2로 구성된 그룹으로부터 선택되는 치환된 알킬이고 ; W2는 독립적으로 Cl, Br 또는 N3이고 ; Z는 3 내지 5이고 ; A1, A2및 A3는 독립적으로, Ala, Arg, Asn, Asp, Cys, Gln, Glu, Gly, His, Ile, Leu, Lys, Met, Phe, Pro, Ser, Thr, Trp, Tyr, 및 Val으로 구성된 그룹으로부터 선택되는 L- 또는 D-배위인 아미노산이며 ; R1은 1 내지 약 20개의 아미노산을 함유하는 펩타이드, 1 내지 약 20개의 탄소원자를 함유하는 아실 또는 설포닐그룹, H 또는 N-말단보호 그룹이고, n, o, p 및 q는 독립적으로 1 또는 0이다.
  45. 제44항에 있어서, R4가 -(CH2)Z-W2이고 Z가 3 내지 4인 화합물.
    ※ 참고사항 : 최초출원 내용에 의하여 공개하는 것임.
KR1019880006671A 1987-06-05 1988-06-03 트립신형 프로테아제의 펩타이드 붕산 억제제 KR910003619B1 (ko)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
US5967087A 1987-06-05 1987-06-05
US059,670 1987-06-05
US07/178,368 US5187157A (en) 1987-06-05 1988-04-06 Peptide boronic acid inhibitors of trypsin-like proteases
US178,368 1988-04-06

Publications (2)

Publication Number Publication Date
KR890000514A true KR890000514A (ko) 1989-03-15
KR910003619B1 KR910003619B1 (ko) 1991-06-07

Family

ID=26739035

Family Applications (1)

Application Number Title Priority Date Filing Date
KR1019880006671A KR910003619B1 (ko) 1987-06-05 1988-06-03 트립신형 프로테아제의 펩타이드 붕산 억제제

Country Status (16)

Country Link
US (1) US5187157A (ko)
EP (1) EP0293881B1 (ko)
JP (1) JPH0730090B2 (ko)
KR (1) KR910003619B1 (ko)
AU (1) AU623592B2 (ko)
CA (1) CA1328332C (ko)
DE (1) DE3878991T2 (ko)
DK (1) DK304488A (ko)
ES (1) ES2046237T3 (ko)
FI (1) FI97297C (ko)
HU (1) HU205141B (ko)
IE (1) IE64787B1 (ko)
IL (1) IL86613A (ko)
NO (1) NO882472L (ko)
NZ (1) NZ224903A (ko)
PT (1) PT87652B (ko)

Families Citing this family (173)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0315574A3 (de) * 1987-11-05 1990-08-22 Hoechst Aktiengesellschaft Renin-Inhibitoren
US5023236A (en) * 1988-04-07 1991-06-11 Corvas, Inc. Factor VII/VIIA active site inhibitors
US5574014A (en) * 1988-04-28 1996-11-12 Thrombosis Research Institute Inhibitors of trypsin-like enzymes
US6313096B1 (en) 1988-04-28 2001-11-06 Trigen Limited Inhibitors of trypsin-like enzymes
EP0341661A3 (en) * 1988-05-11 1991-05-02 The Du Pont Merck Pharmaceutical Company Peptide-drug compositions containing alpha-aminoboronic acid derivatives
DE3827340A1 (de) * 1988-08-12 1990-02-15 Hoechst Ag Verwendung von (alpha)-aminoboronsaeure-derivaten zur prophylaxe und behandlung von viruserkrankungen
US5580560A (en) * 1989-11-13 1996-12-03 Novo Nordisk A/S Modified factor VII/VIIa
US5252463A (en) * 1990-06-22 1993-10-12 The Du Pont Merck Pharmaceutical Company Clipsin, a chymotrypsin-like protease and method of using same
GB9017694D0 (en) * 1990-08-13 1990-09-26 Sandoz Ltd Improvements in or relating to organic chemistry
GB9024129D0 (en) * 1990-11-06 1990-12-19 Thrombosis Research Trust Inhibitors and substrates of thrombin
WO1992019707A1 (en) * 1991-04-30 1992-11-12 The Procter & Gamble Company Liquid detergents with an aryl boronic acid
US5635477A (en) * 1991-09-30 1997-06-03 The Dupont Merck Pharmaceutical Company Cyclic compounds useful as inhibitors of platelet glycoprotein IIB/IIIA
US6825169B1 (en) 1991-10-22 2004-11-30 Trustees Of Tufts College Inhibitors of dipeptidyl-aminopeptidase type IV
SE9103612D0 (sv) * 1991-12-04 1991-12-04 Astra Ab New peptide derivatives
WO1993011215A1 (en) * 1991-12-04 1993-06-10 The Procter & Gamble Company Liquid laundry detergents with citric acid, cellulase, and boric-diol complex to inhibit proteolytic enzyme
DK0583534T3 (da) * 1992-08-14 1997-06-16 Procter & Gamble Flydende detergenter, der indeholder et peptidaldehyd
US5442100A (en) * 1992-08-14 1995-08-15 The Procter & Gamble Company β-aminoalkyl and β-N-peptidylaminoalkyl boronic acids
ES2098484T3 (es) * 1992-08-14 1997-05-01 Procter & Gamble Detergentes liquidos que contienen un acido alfa-amino-boronico.
US5576283A (en) * 1992-08-14 1996-11-19 The Procter & Gamble Company Liquid detergents containing a peptide aldehyde
US5354491A (en) * 1992-08-14 1994-10-11 The Procter & Gamble Company Liquid detergent compositions containing protease and certain β-aminoalkylboronic acids and esters
US5582762A (en) * 1992-08-14 1996-12-10 The Procter & Gamble Company Liquid detergents containing a peptide trifluoromethyl ketone
EP0675899B1 (en) * 1992-12-15 1999-03-17 Corvas International, Inc. NOVEL INHIBITORS OF FACTOR Xa
IL108031A0 (en) * 1992-12-22 1994-04-12 Procter & Gamble Difluoro pentapeptide derivatives and pharmaceutical compositions containing them
FR2701951B1 (fr) * 1993-02-24 1995-06-09 Adir Nouveaux derives peptidiques de l'acide boronique, leur procede de preparation et les compositions pharmaceutiques qui les contiennent.
PL310940A1 (en) * 1993-03-03 1996-01-08 Sandoz Ltd Organic compounds
US5384410A (en) * 1993-03-24 1995-01-24 The Du Pont Merck Pharmaceutical Company Removal of boronic acid protecting groups by transesterification
US5563127A (en) * 1993-03-24 1996-10-08 The Dupont Merck Pharmaceutical Company Boronic acid and ester inhibitors of thrombin
AU6448794A (en) * 1993-03-24 1994-10-11 Du Pont Merck Pharmaceutical Company, The Boronic acid and ester inhibitors of thrombin
US5656600A (en) * 1993-03-25 1997-08-12 Corvas International, Inc. α-ketoamide derivatives as inhibitors of thrombosis
US5658885A (en) * 1993-04-27 1997-08-19 The Dupont Merck Pharmaceutical Company Amidino and guanidino substituted boronic acid inhibitors of trypsin-like enzymes
US5780631A (en) * 1993-06-03 1998-07-14 Astra Aktiebolag Starting materials in the synthesis of thrombin and kininogenase inhibitors
US6984627B1 (en) 1993-06-03 2006-01-10 Astrazeneca Ab Peptide derivatives
SE9301916D0 (sv) * 1993-06-03 1993-06-03 Ab Astra New peptides derivatives
IL111175A0 (en) * 1993-10-07 1994-12-29 Du Pont Merck Pharma Electrophilic peptide analogs as inhibitors of trypsin-like serine proteases and pharmaceutical compositions containing them
AU7922794A (en) * 1993-10-07 1995-05-01 Du Pont Merck Pharmaceutical Company, The Boropeptide inhibitors of thrombin which contain a substituted pyrrolidine ring
IL111176A0 (en) * 1993-10-07 1994-12-29 Du Pont Merck Pharma Dipeptide boronic acid inhibitors of trypsin-like enzymes and pharmaceutical compositions containing them
US6060462A (en) * 1993-10-20 2000-05-09 Dupont Pharmaceuticals Company Electrophilic peptide analogs as inhibitors of trypsin-like enzymes
US5446056A (en) * 1993-11-24 1995-08-29 The Du Pont Merck Pharmaceutical Company Isoxazoline compounds useful as fibrinogen receptor antagonists
GB9401483D0 (en) * 1994-01-26 1994-03-23 Sandoz Ltd Organic compounds
US5436229A (en) * 1994-03-04 1995-07-25 Eli Lilly And Company Bisulfite adducts of arginine aldehydes
CA2143533A1 (en) * 1994-03-04 1995-09-05 Kenneth D. Kurz Antithrombotic agents
US5439888A (en) * 1994-03-04 1995-08-08 Eli Lilly And Company Antithrombotic agents
US5705487A (en) * 1994-03-04 1998-01-06 Eli Lilly And Company Antithrombotic agents
US5602101A (en) * 1994-03-04 1997-02-11 Eli Lilly And Company Antithrombotic agents
US5484772A (en) * 1994-03-04 1996-01-16 Eli Lilly And Company Antithrombotic agents
US5726159A (en) * 1994-03-04 1998-03-10 Eli Lilly And Company Antithrombotic agents
US5885967A (en) * 1994-03-04 1999-03-23 Eli Lilly And Company Antithrombotic agents
US5707966A (en) * 1994-03-04 1998-01-13 Eli Lilly And Company Antithrombotic agents
ZA951618B (en) * 1994-03-04 1996-08-27 Lilly Co Eli Antithrombotic agents
US5488037A (en) * 1994-03-04 1996-01-30 Eli Lilly And Company Antithrombotic agents
US5693617A (en) * 1994-03-15 1997-12-02 Proscript, Inc. Inhibitors of the 26s proteolytic complex and the 20s proteasome contained therein
FR2718451B1 (fr) * 1994-04-12 1996-05-10 Synthelabo Dérivés de peptides boroniques, leur préparation et leur application en thérapeutique.
FR2718448B3 (fr) * 1994-04-12 1996-02-09 Synthelabo Dérivés d'acides aminoboroniques, leur préparation et leur utilisation comme intermédiaires de synthèse.
DE4421052A1 (de) 1994-06-17 1995-12-21 Basf Ag Neue Thrombininhibitoren, ihre Herstellung und Verwendung
FR2721611B1 (fr) * 1994-06-22 1996-09-27 Adir Nouveaux dérivés peptidiques de l'acide boronique, leur procédé de préparation et les compositions pharmaceutiques qui les contiennent .
US6083903A (en) * 1994-10-28 2000-07-04 Leukosite, Inc. Boronic ester and acid compounds, synthesis and uses
SE9404196D0 (sv) * 1994-12-02 1994-12-02 Astra Ab New antithrombotic formulation
SK104697A3 (en) * 1995-02-17 1998-11-04 Basf Ag Novel dipeptide amidines as thrombin inhibitors
US5914319A (en) * 1995-02-27 1999-06-22 Eli Lilly And Company Antithrombotic agents
US5710130A (en) * 1995-02-27 1998-01-20 Eli Lilly And Company Antithrombotic agents
US5639739A (en) * 1995-03-24 1997-06-17 The Dupont Merck Pharmaceutical Company Imidazole containing aminoboronic acids
US5731439A (en) * 1995-03-24 1998-03-24 The Dupont Merck Pharmaceutical Company Piperidine containing aminobornic acids
SA96170106A (ar) 1995-07-06 2005-12-03 أسترا أكتيبولاج مشتقات حامض أميني جديدة
KR100490807B1 (ko) * 1995-11-28 2005-10-14 세파론, 인코포레이티드 시스테인및세린프로테아제의d-아미노산함유억제제
AR005245A1 (es) * 1995-12-21 1999-04-28 Astrazeneca Ab Prodrogas de inhibidores de trombina, una formulación farmaceutica que las comprende, el uso de dichas prodrogas para la manufactura de un medicamento y un procedimiento para su preparacion
US5760028A (en) * 1995-12-22 1998-06-02 The Dupont Merck Pharmaceutical Company Integrin receptor antagonists
US5942544A (en) * 1996-02-22 1999-08-24 Dupont Pharmaceuticals Company α-branched anilines, toluenes, and analogs thereof as factor Xa inhibitors
FR2745288B1 (fr) * 1996-02-27 1998-04-17 Adir Nouveaux derives de l'acide boronique, leur procede de preparation et les compositions pharmaceutiques qui les contiennent
SE9602263D0 (sv) 1996-06-07 1996-06-07 Astra Ab New amino acid derivatives
US5965532A (en) * 1996-06-28 1999-10-12 Trustees Of Tufts College Multivalent compounds for crosslinking receptors and uses thereof
SE9602646D0 (sv) 1996-07-04 1996-07-04 Astra Ab Pharmaceutically-useful compounds
US6004955A (en) * 1996-08-15 1999-12-21 Dupont Pharmaceuticals Company Cyclic carbamates and isoxazolidines as IIb/IIIa antagonists
EP0929640A1 (en) * 1996-09-24 1999-07-21 The Procter & Gamble Company Liquid detergents containing proteolytic enzyme and protease inhibitors
JP2000506932A (ja) 1996-09-24 2000-06-06 ザ、プロクター、エンド、ギャンブル、カンパニー タンパク質分解酵素およびプロテアーゼインヒビターを含有した液体洗濯洗剤組成物
US6165966A (en) * 1996-09-24 2000-12-26 The Procter & Gamble Company Liquid detergents containing proteolytic enzyme and protease inhibitors
US5968782A (en) * 1996-12-04 1999-10-19 Brigham And Womens's Hospital, Inc. Mast cell protease that cleaves fibrinogen
WO1998033812A1 (en) * 1997-02-05 1998-08-06 Brigham And Women's Hospital, Inc. Mast cell protease peptide inhibitors
US6040145A (en) * 1997-05-07 2000-03-21 Tufts University Potentiation of the immune response
US6100234A (en) 1997-05-07 2000-08-08 Tufts University Treatment of HIV
AR013084A1 (es) 1997-06-19 2000-12-13 Astrazeneca Ab Derivados de amidino utiles como inhibidores de la trombina, composicion farmaceutica, utilizacion de dichos compuestos para la preparacion demedicamentos y proceso para la preparacion de los compuestos mencionados
ES2239806T3 (es) 1997-06-19 2005-10-01 Bristol-Myers Squibb Pharma Company Inhibidores del factor xa con un grupo de especificidad neutro p1.
KR100458403B1 (ko) * 1997-09-29 2004-11-26 포인트 써러퓨틱스, 인크. 생체외 조혈세포의 자극방법
ZA988735B (en) * 1997-10-06 2000-03-23 Du Pont Pharm Co An efficient method for the conversion of nitriles to amidines.
US6204384B1 (en) 1997-11-26 2001-03-20 Corvas International, Inc. Substituted 3-amino-2-hydroxyphenylacetamide derivatives as enzyme inhibitors (II)
US6011047A (en) * 1997-11-26 2000-01-04 Corvas International Inc. Substituted 3-amino-2-hydroxyphenylacetamide derivatives as enzyme inhibitors
SE9704543D0 (sv) 1997-12-05 1997-12-05 Astra Ab New compounds
EP1051431A1 (de) 1998-01-26 2000-11-15 Basf Aktiengesellschaft Thrombininhibitoren
AU3213799A (en) 1998-04-01 1999-10-18 Du Pont Pharmaceuticals Company Integrin antagonists
EP1075266A1 (en) * 1998-05-04 2001-02-14 Point Therapeutics, Inc. Hematopoietic stimulation
PT1084129E (pt) 1998-06-05 2003-06-30 Point Therapeutics Inc Compostos de boroprolina ciclica
US6979697B1 (en) * 1998-08-21 2005-12-27 Point Therapeutics, Inc. Regulation of substrate activity
SE9804313D0 (sv) 1998-12-14 1998-12-14 Astra Ab New compounds
AU3127900A (en) 1998-12-23 2000-07-31 Du Pont Pharmaceuticals Company Thrombin or factor xa inhibitors
CA2355792A1 (en) 1999-01-13 2000-07-20 Astrazeneca Ab New amidinobenzylamine derivatives and their use as thrombin inhibitors
AR023510A1 (es) 1999-04-21 2002-09-04 Astrazeneca Ab Un equipo de partes, formulacion farmaceutica y uso de un inhibidor de trombina.
US6890904B1 (en) * 1999-05-25 2005-05-10 Point Therapeutics, Inc. Anti-tumor agents
US6649593B1 (en) * 1999-10-13 2003-11-18 Tularik Inc. Modulators of SREBP processing
SE0001803D0 (sv) 2000-05-16 2000-05-16 Astrazeneca Ab New compounds i
US6433186B1 (en) 2000-08-16 2002-08-13 Astrazeneca Ab Amidino derivatives and their use as thormbin inhibitors
US7129233B2 (en) 2000-12-01 2006-10-31 Astrazeneca Ab Mandelic acid derivatives and their use as thrombin inhibitors
AR035216A1 (es) 2000-12-01 2004-05-05 Astrazeneca Ab Derivados de acido mandelico ,derivados farmaceuticamente aceptables, uso de estos derivados para la fabricacion de medicamentos, metodos de tratamiento ,procesos para la preparacion de estos derivados, y compuestos intermediarios
US6586615B1 (en) 2001-01-10 2003-07-01 Bristol-Myers Squibb Company α-aminoboronic acids prepared by novel synthetic methods
DK1355910T3 (da) 2001-01-25 2011-06-27 Us Of America Represented By The Secretary Dept Of Health And Human Services Formulering af borsyreforbindelser
AR034517A1 (es) 2001-06-21 2004-02-25 Astrazeneca Ab Formulacion farmaceutica
US6777431B2 (en) 2001-07-13 2004-08-17 Corvas International, Inc. Non-convalent thrombin inhibitors
US20060014697A1 (en) * 2001-08-22 2006-01-19 Travis Mickle Pharmaceutical compositions for prevention of overdose or abuse
SE0201659D0 (sv) 2002-05-31 2002-05-31 Astrazeneca Ab Modified release pharmaceutical formulation
SE0201661D0 (sv) 2002-05-31 2002-05-31 Astrazeneca Ab New salts
EP1578434A2 (en) * 2002-07-09 2005-09-28 Point Therapeutics, Inc. Methods and compositions relating to isoleucine boroproline compounds
US20050282757A1 (en) * 2002-09-09 2005-12-22 Trigen Limited Peptide boronic acid compounds useful in anticoagulation
US20050176651A1 (en) * 2002-09-09 2005-08-11 Trigen Limited Peptide boronic acids useful in making salts thereof
US20060084592A1 (en) * 2002-09-09 2006-04-20 Trigen Limited Peptide boronic acid inhibitors
US20050119226A1 (en) * 2003-09-09 2005-06-02 Trigen Limited Methods for synthesizing organoboronic compounds and products thereof
US7112572B2 (en) * 2002-09-09 2006-09-26 Trigen Limited Multivalent metal salts of boronic acids
US7781424B2 (en) 2003-05-27 2010-08-24 Astrazeneca Ab Modified release pharmaceutical formulation
US7576206B2 (en) * 2003-08-14 2009-08-18 Cephalon, Inc. Proteasome inhibitors and methods of using the same
US7223745B2 (en) * 2003-08-14 2007-05-29 Cephalon, Inc. Proteasome inhibitors and methods of using the same
GB0405272D0 (en) * 2004-03-09 2004-04-21 Trigen Ltd Compounds
BRPI0509587A (pt) * 2004-03-30 2007-09-25 Millennium Pharm Inc processo em grande escala para preparar um composto de éster borÈnico, aminoborÈnico e composição que compreende um solvente de éter
US7795205B2 (en) 2004-04-12 2010-09-14 Canyon Pharmaceuticals, Inc. Methods for effecting regression of tumor mass and size in a metastasized pancreatic tumor
US20060063719A1 (en) * 2004-09-21 2006-03-23 Point Therapeutics, Inc. Methods for treating diabetes
US7468383B2 (en) * 2005-02-11 2008-12-23 Cephalon, Inc. Proteasome inhibitors and methods of using the same
TW200827336A (en) 2006-12-06 2008-07-01 Astrazeneca Ab New crystalline forms
SG10201508712QA (en) 2007-08-06 2015-11-27 Millenium Pharmaceuticals Inc Proteasome inhibitors
WO2009071601A1 (en) * 2007-12-03 2009-06-11 Obe Therapy Biotechnology Boropeptide inhibitors of enteropeptidase and their uses in treatment of obesity, overweight and/or diseases associated with an abnormal fat metabolism
US10793515B2 (en) 2008-03-19 2020-10-06 Aurimmed Pharma, Inc. Compounds advantageous in the treatment of central nervous system diseases and disorders
US9212155B2 (en) 2008-03-19 2015-12-15 Aurimmed Pharma, Inc. Compounds advantageous in the treatment of central nervous system diseases and disorders
KR101672884B1 (ko) 2008-03-19 2016-11-04 오림드 파마, 인코포레이티드 중추신경계 질환 및 질병 치료에 유효한 신규 화합물
GB0807828D0 (en) * 2008-04-29 2008-06-04 Vantia Ltd Aminopyridine derivatives
EP2733147A1 (en) 2008-06-17 2014-05-21 Millennium Pharmaceuticals, Inc. Boronate ester compounds and pharmaceutical compositions thereof
AR075090A1 (es) 2008-09-29 2011-03-09 Millennium Pharm Inc Derivados de acido 1-amino-2-ciclobutiletilboronico inhibidores de proteosoma,utiles como agentes anticancerigenos, y composiciones farmaceuticas que los comprenden.
EA201170527A1 (ru) * 2008-10-01 2011-10-31 Др. Редди'С Лабораторис Лтд. Фармацевтические композиции, включающие соединения бороновой кислоты
US20120149663A1 (en) 2009-08-18 2012-06-14 Georgetown University Boronic acid compositions and methods related to cancer
GB0918922D0 (en) 2009-10-28 2009-12-16 Vantia Ltd Aminopyridine derivatives
GB0918923D0 (en) 2009-10-28 2009-12-16 Vantia Ltd Aminothiazole derivatives
GB0918924D0 (en) 2009-10-28 2009-12-16 Vantia Ltd Azaindole derivatives
CA2785300A1 (en) 2009-12-22 2011-07-21 Cephalon, Inc. Proteasome inhibitors and processes for their preparation, purification and use
KR20130036228A (ko) 2010-03-31 2013-04-11 밀레니엄 파머슈티컬스 인코퍼레이티드 1-아미노-2-사이클로프로필에틸보론산의 유도체
WO2012047845A1 (en) 2010-10-05 2012-04-12 App Pharmaceuticals Bortezomib formulations stabilised with boric
GB2494851A (en) 2011-07-07 2013-03-27 Kalvista Pharmaceuticals Ltd Plasma kallikrein inhibitors
US10293048B2 (en) 2012-03-02 2019-05-21 Dr. Reddy's Laboratories Limited Pharmaceutical compositions comprising boronic acid compounds
GB201212081D0 (en) 2012-07-06 2012-08-22 Kalvista Pharmaceuticals Ltd New polymorph
GB201300304D0 (en) 2013-01-08 2013-02-20 Kalvista Pharmaceuticals Ltd Benzylamine derivatives
PH12015501492B1 (en) 2013-01-08 2015-09-28 Kalvista Pharmaceuticals Ltd Benzylamine derivatives
GB2510407A (en) 2013-02-04 2014-08-06 Kalvista Pharmaceuticals Ltd Aqueous suspensions of kallikrein inhibitors for parenteral administration
US10023611B2 (en) 2013-04-16 2018-07-17 Cipla Limited Process for the preparation of bortezomib mannitol ester
SG11201509303WA (en) 2013-05-23 2015-12-30 Kalvista Pharmaceuticals Ltd Heterocyclic derivates
US10478445B2 (en) 2013-07-03 2019-11-19 Georgetown University Boronic acid derivatives of resveratrol for activating deacetylase enzymes
GB2517908A (en) 2013-08-14 2015-03-11 Kalvista Pharmaceuticals Ltd Bicyclic inhibitors
RU2674028C2 (ru) 2013-08-14 2018-12-04 Калвиста Фармасьютикалз Лимитед Ингибиторы ферментов
TWI636047B (zh) 2013-08-14 2018-09-21 英商卡爾維斯塔製藥有限公司 雜環衍生物
WO2015117136A1 (en) 2014-02-03 2015-08-06 Ohio State Innovation Foundation Boronic acid esters and pharmaceutical formulations thereof
WO2015179443A1 (en) 2014-05-20 2015-11-26 Millennium Pharmaceuticals. Inc. Boron-containing proteasome inhibitors for use after primary cancer therapy
GB201421085D0 (en) 2014-11-27 2015-01-14 Kalvista Pharmaceuticals Ltd New enzyme inhibitors
GB201421088D0 (en) 2014-11-27 2015-01-14 Kalvista Pharmaceuticals Ltd New enzyme inhibitors
GB201421083D0 (en) 2014-11-27 2015-01-14 Kalvista Pharmaceuticals Ltd Enzyme inhibitors
MA41505A (fr) 2015-02-11 2017-12-19 Millennium Pharm Inc Nouvelle forme cristalline d'un inhibiteur de protéasome
US20180243217A1 (en) 2015-03-17 2018-08-30 Leon-Nanodrugs Gmbh Nanoparticles comprising a stabilized boronic acid compound
CN109311847B (zh) 2016-05-31 2021-07-06 卡尔维斯塔制药有限公司 作为血浆激肽释放酶抑制剂的吡唑衍生物
GB201609603D0 (en) 2016-06-01 2016-07-13 Kalvista Pharmaceuticals Ltd Polymorphs of N-[(6-cyano-2-fluoro-3-methoxyphenyl)Methyl]-3-(methoxymethyl)-1-({4-[(2-ox opyridin-1-YL)Methyl]phenyl}methyl)pyrazole-4-carboxamide
GB201609607D0 (en) 2016-06-01 2016-07-13 Kalvista Pharmaceuticals Ltd Polymorphs of N-(3-Fluoro-4-methoxypyridin-2-yl)methyl)-3-(methoxymethyl)-1-({4-((2-oxopy ridin-1-yl)methyl)phenyl}methyl)pyrazole-4-carboxamide and salts
GB201719881D0 (en) 2017-11-29 2018-01-10 Kalvista Pharmaceuticals Ltd Solid forms of plasma kallikrein inhibitor and salts thereof
US11234939B2 (en) 2017-11-29 2022-02-01 Kalvista Pharmaceuticals Limited Dosage forms comprising a plasma kallikrein inhibitor
GB201910116D0 (en) 2019-07-15 2019-08-28 Kalvista Pharmaceuticals Ltd Treatments of hereditary angioedema
GB201910125D0 (en) 2019-07-15 2019-08-28 Kalvista Pharmaceuticals Ltd Treatments of angioedema
EP4010333A1 (en) 2019-08-09 2022-06-15 Kalvista Pharmaceuticals Limited Plasma kallikrein inhibitors
GB201918994D0 (en) 2019-12-20 2020-02-05 Kalvista Pharmaceuticals Ltd Treatments of diabetic macular edema and impaired visual acuity
GB2591730A (en) 2019-12-09 2021-08-11 Kalvista Pharmaceuticals Ltd New polymorphs
WO2022079446A1 (en) 2020-10-15 2022-04-21 Kalvista Pharmaceuticals Limited Treatments of angioedema
WO2022084693A1 (en) 2020-10-23 2022-04-28 Kalvista Pharmaceuticals Limited Treatments of angioedema
EP4291186A1 (en) 2021-02-09 2023-12-20 Kalvista Pharmaceuticals Limited Treatments of hereditary angioedema
WO2023002219A1 (en) 2021-07-23 2023-01-26 Kalvista Pharmaceuticals Limited Treatments of hereditary angioedema
WO2023209381A1 (en) 2022-04-27 2023-11-02 Kalvista Pharmaceuticals Limited Formulations of a plasma kallikrein inhibitor

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4318904A (en) * 1980-04-25 1982-03-09 Research Corporation Peptide affinity labels for thrombin and other trypsin-like proteases
US4537773A (en) * 1983-12-05 1985-08-27 E. I. Du Pont De Nemours And Company α-Aminoboronic acid derivatives
US4499082A (en) * 1983-12-05 1985-02-12 E. I. Du Pont De Nemours And Company α-Aminoboronic acid peptides
JPS61112018A (ja) * 1984-11-06 1986-05-30 Mitsubishi Chem Ind Ltd 線溶増強剤
NZ223148A (en) * 1987-01-16 1989-10-27 Merrell Dow Pharma Peptide derivatives having peptidase inhibition activity

Also Published As

Publication number Publication date
IE881666L (en) 1988-12-05
KR910003619B1 (ko) 1991-06-07
PT87652B (pt) 1992-09-30
JPH0730090B2 (ja) 1995-04-05
NO882472D0 (no) 1988-06-03
HUT49629A (en) 1989-10-30
EP0293881B1 (en) 1993-03-10
IE64787B1 (en) 1995-09-06
EP0293881A2 (en) 1988-12-07
CA1328332C (en) 1994-04-05
NO882472L (no) 1988-12-06
DK304488D0 (da) 1988-06-03
FI882638A0 (fi) 1988-06-03
EP0293881A3 (en) 1990-05-30
JPS6463583A (en) 1989-03-09
US5187157A (en) 1993-02-16
PT87652A (pt) 1988-07-01
NZ224903A (en) 1990-02-26
FI97297C (fi) 1996-11-25
FI882638A (fi) 1988-12-06
DE3878991D1 (de) 1993-04-15
AU623592B2 (en) 1992-05-21
IL86613A0 (en) 1988-11-30
DE3878991T2 (de) 1993-07-15
FI97297B (fi) 1996-08-15
DK304488A (da) 1988-12-06
IL86613A (en) 1993-04-04
HU205141B (en) 1992-03-30
AU1733288A (en) 1988-12-08
ES2046237T3 (es) 1994-02-01

Similar Documents

Publication Publication Date Title
KR890000514A (ko) 트립신형 프로테아제의 펩타이드 붕산 억제제
Gregory et al. The primary structure of human urogastrone
Nestor Jr et al. Synthesis and biological activity of some very hydrophobic superagonist analogs of luteinizing hormone-releasing hormone
AU593820B2 (en) Novel polypeptides with a blood coagulation-inhibiting action, processes for their preparation and isolation, their use and agents containing them
US5607858A (en) Peptide amides, processes for the preparation thereof and agents containing these as fibrin/thrombin clotting inhibitors
CA1286847C (en) Peptide derivatives analogous to pepstatin, which inhibit renin and acid proteases
PT95661A (pt) Processo de preparacao de peptidos ciclicos e de composicoes farmaceuticas que os contem
TW343198B (en) Cyclopeptides useful as adhesion inhibitors, process for the preparation thereof, and pharmaceutical composition containing them
EA000088B1 (ru) Ингибиторы тромбина, основанные на аминокислотной последовательности гирудина
KR970015598A (ko) 환상 결합 억제제
KR850000415B1 (ko) 아실펩타이드의 제조방법
Lin et al. Trypsin inhibitor from the seeds of Acacia confusa
Krstenansky et al. Development of MDL 28,050, a small stable antithrombin agent based on a functional domain of the leech protein, hirudin
Folk 2 Carboxypeptidase B
Odani et al. Proteinase Inhibators from a Mimosoideae Legume
CA2227198A1 (en) Cysteine protease inhibitors for use in treatment of ige mediated allergic diseases
US4943562A (en) Tetra- and pentapeptides containing the lysyl-arginyl-aspartyl sequence and their applications as medicines, particularly anti-thrombotic medicines
Mebs et al. Hemolysins and proteinase inhibitors from sea anemones of the Gulf of Aqaba
Suzuki et al. Purification and characterization of an inhibitor of the cysteine protease from the hemolymph of Sarcophaga peregrina larvae.
HIRAO et al. Purification and characterization of cathepsin B from monkey skeletal muscle
KR880013977A (ko) 항응고제인 사이클릭 펩타이드
Moreau et al. Cysteine‐proteinase‐inhibiting function of T kininogen and of its proteolytic fragments
Chung et al. Structural and functional studies on C4b-binding protein, a regulatory component of the human complement system
CA2085465C (en) Thrombin inhibitors based on the amino acid sequence of hirudin
Hsieh et al. Angiotensin II analogs. 12. Role of the aromatic ring of position 8 phenylalanine in pressor activity

Legal Events

Date Code Title Description
A201 Request for examination
E902 Notification of reason for refusal
G160 Decision to publish patent application
E701 Decision to grant or registration of patent right
GRNT Written decision to grant
FPAY Annual fee payment

Payment date: 19960403

Year of fee payment: 6

LAPS Lapse due to unpaid annual fee