SK285588B6 - Prekurzory inhibítorov trombínu, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ichpoužitie - Google Patents

Prekurzory inhibítorov trombínu, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ichpoužitie Download PDF

Info

Publication number: SK285588B6
Authority: SK; Slovakia
Prior art keywords: pab; cgl; aze; alkyl; formula
Prior art date: 1995-12-21

Application number

SK821-98A

Other languages

English (en)

Slovak (sk)

Other versions

SK82198A3 (en

Inventor

Karl Thomas Antonsson

David Gustafsson

Kurt-J�Rgen Hoffmann

Jan-Erik NYSTR�M

Henrik S�RENSEN

Mikael Sell�N

Original Assignee

Astrazeneca Ab

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.)

1995-12-21

Filing date

1996-12-17

Publication date

2007-04-05

1995-12-21 Priority claimed from GB9526273A external-priority patent/GB9526273D0/en

1996-02-15 Priority claimed from SE9600556A external-priority patent/SE9600556D0/xx

1996-12-17 Application filed by Astrazeneca Ab filed Critical Astrazeneca Ab

1998-12-02 Publication of SK82198A3 publication Critical patent/SK82198A3/sk

2007-04-05 Publication of SK285588B6 publication Critical patent/SK285588B6/sk

Links

238000000034 method Methods 0.000 title claims abstract description 64
238000002360 preparation method Methods 0.000 title claims abstract description 20
230000008569 process Effects 0.000 title claims abstract description 8
239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 5
229940122388 Thrombin inhibitor Drugs 0.000 title description 24
239000003868 thrombin inhibitor Substances 0.000 title description 24
239000000651 prodrug Substances 0.000 title description 7
229940002612 prodrug Drugs 0.000 title description 7
150000001875 compounds Chemical class 0.000 claims abstract description 289
125000000217 alkyl group Chemical group 0.000 claims abstract description 111
229910052736 halogen Chemical group 0.000 claims abstract description 37
150000002367 halogens Chemical group 0.000 claims abstract description 35
108090000190 Thrombin Proteins 0.000 claims abstract description 29
125000005037 alkyl phenyl group Chemical group 0.000 claims abstract description 29
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 28
229960004072 thrombin Drugs 0.000 claims abstract description 28
-1 R8 represents H Chemical group 0.000 claims abstract description 19
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 19
150000003839 salts Chemical class 0.000 claims abstract description 16
125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims abstract description 14
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 14
125000004423 acyloxy group Chemical group 0.000 claims abstract description 12
125000002947 alkylene group Chemical group 0.000 claims abstract description 12
208000007536 Thrombosis Diseases 0.000 claims abstract description 10
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 9
238000011282 treatment Methods 0.000 claims abstract description 9
239000003146 anticoagulant agent Substances 0.000 claims abstract description 8
125000000719 pyrrolidinyl group Chemical group 0.000 claims abstract description 8
229940127219 anticoagulant drug Drugs 0.000 claims abstract description 7
230000005764 inhibitory process Effects 0.000 claims abstract description 6
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 4
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 4
125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 4
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125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 3
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims abstract description 3
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 claims abstract description 3
125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract 7
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 2
150000001409 amidines Chemical group 0.000 claims description 32
125000003545 alkoxy group Chemical group 0.000 claims description 28
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 28
125000004122 cyclic group Chemical group 0.000 claims description 22
229910052799 carbon Inorganic materials 0.000 claims description 14
229910052739 hydrogen Inorganic materials 0.000 claims description 13
239000000460 chlorine Substances 0.000 claims description 11
239000002253 acid Chemical class 0.000 claims description 9
125000000753 cycloalkyl group Chemical group 0.000 claims description 9
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210000004369 blood Anatomy 0.000 claims description 8
239000008280 blood Substances 0.000 claims description 8
125000001424 substituent group Chemical group 0.000 claims description 8
238000004519 manufacturing process Methods 0.000 claims description 7
GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 6
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150000002148 esters Chemical group 0.000 claims description 3
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150000004703 alkoxides Chemical class 0.000 claims description 2
239000003795 chemical substances by application Substances 0.000 claims description 2
239000003085 diluting agent Substances 0.000 claims description 2
238000005809 transesterification reaction Methods 0.000 claims description 2
239000004480 active ingredient Substances 0.000 claims 4
125000005843 halogen group Chemical group 0.000 claims 4
125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 abstract description 2
125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract 1
125000004400 (C1-C12) alkyl group Chemical group 0.000 abstract 1
125000004209 (C1-C8) alkyl group Chemical group 0.000 abstract 1
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239000002585 base Substances 0.000 description 11
PQJJJMRNHATNKG-UHFFFAOYSA-N ethyl bromoacetate Chemical compound CCOC(=O)CBr PQJJJMRNHATNKG-UHFFFAOYSA-N 0.000 description 11
239000000047 product Substances 0.000 description 11
239000003112 inhibitor Substances 0.000 description 10
239000012074 organic phase Substances 0.000 description 10
238000007911 parenteral administration Methods 0.000 description 10
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238000006243 chemical reaction Methods 0.000 description 9
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238000012360 testing method Methods 0.000 description 9
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
230000035602 clotting Effects 0.000 description 8
230000000694 effects Effects 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
125000006239 protecting group Chemical group 0.000 description 8
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JHVLLYQQQYIWKX-UHFFFAOYSA-N benzyl 2-bromoacetate Chemical compound BrCC(=O)OCC1=CC=CC=C1 JHVLLYQQQYIWKX-UHFFFAOYSA-N 0.000 description 7
230000001225 therapeutic effect Effects 0.000 description 7
LSTRKXWIZZZYAS-UHFFFAOYSA-N 2-bromoacetyl bromide Chemical compound BrCC(Br)=O LSTRKXWIZZZYAS-UHFFFAOYSA-N 0.000 description 6
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230000015572 biosynthetic process Effects 0.000 description 5
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238000004128 high performance liquid chromatography Methods 0.000 description 5
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SYZRZLUNWVNNNV-UHFFFAOYSA-N 2-bromoacetyl chloride Chemical compound ClC(=O)CBr SYZRZLUNWVNNNV-UHFFFAOYSA-N 0.000 description 4
KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 4
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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
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- 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
- 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
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/02—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link
- C07K5/022—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2
- C07K5/0222—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -X-C(=O)-(C)n-N-C-C(=O)-Y-; X and Y being heteroatoms; n being 1 or 2 with the first amino acid being heterocyclic, e.g. Pro, Trp
- 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
- C07K5/06—Dipeptides
- C07K5/06008—Dipeptides with the first amino acid being neutral
- C07K5/06078—Dipeptides with the first amino acid being neutral and aromatic or cycloaliphatic
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
General Health & Medical Sciences (AREA)
Medicinal Chemistry (AREA)
Molecular Biology (AREA)
Engineering & Computer Science (AREA)
Proteomics, Peptides & Aminoacids (AREA)
Genetics & Genomics (AREA)
Biochemistry (AREA)
Biophysics (AREA)
Bioinformatics & Cheminformatics (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Pharmacology & Pharmacy (AREA)
Hematology (AREA)
Diabetes (AREA)
Cardiology (AREA)
Vascular Medicine (AREA)
Heart & Thoracic Surgery (AREA)
Urology & Nephrology (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)

SK821-98A 1995-12-21 1996-12-17 Prekurzory inhibítorov trombínu, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ichpoužitie SK285588B6 (sk)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
GB9526273A GB9526273D0 (en)	1995-12-21	1995-12-21	New prodrugs
SE9600556A SE9600556D0 (sv)	1996-02-15	1996-02-15	New prodrugs
PCT/SE1996/001680 WO1997023499A1 (fr)	1995-12-21	1996-12-17	Promedicaments d'inhibiteurs de thrombine

Publications (2)

Publication Number	Publication Date
SK82198A3 SK82198A3 (en)	1998-12-02
SK285588B6 true SK285588B6 (sk)	2007-04-05

Family

ID=26308368

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK821-98A SK285588B6 (sk)	1995-12-21	1996-12-17	Prekurzory inhibítorov trombínu, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ichpoužitie

Country Status (29)

Country	Link
US (4)	US5965692A (fr)
EP (3)	EP0869966B1 (fr)
JP (1)	JP2000504313A (fr)
KR (1)	KR100458545B1 (fr)
AR (1)	AR005245A1 (fr)
AT (2)	ATE204292T1 (fr)
BR (1)	BR9612148A (fr)
CA (1)	CA2238737A1 (fr)
DE (3)	DE69634492T2 (fr)
DK (2)	DK0995755T3 (fr)
EE (1)	EE04022B1 (fr)
ES (2)	ES2163916T3 (fr)
HU (1)	HUP9900115A3 (fr)
IL (1)	IL124857A0 (fr)
IS (1)	IS1836B (fr)
LU (1)	LU91172I2 (fr)
MX (1)	MX9804623A (fr)
MY (1)	MY121222A (fr)
NL (1)	NL300179I2 (fr)
NO (1)	NO982809L (fr)
NZ (2)	NZ324902A (fr)
PL (1)	PL187468B1 (fr)
PT (1)	PT995755E (fr)
RU (1)	RU2176644C2 (fr)
SI (2)	SI0869966T1 (fr)
SK (1)	SK285588B6 (fr)
TR (1)	TR199801151T2 (fr)
TW (2)	TWI238827B (fr)
WO (1)	WO1997023499A1 (fr)

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SE0103369D0 (sv) *	2001-10-09	2001-10-09	Astrazeneca Ab	Pharmaceutical formulation
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SE0201659D0 (sv)	2002-05-31	2002-05-31	Astrazeneca Ab	Modified release pharmaceutical formulation
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1996
- 1996-12-09 TW TW091115525A patent/TWI238827B/zh active
- 1996-12-09 TW TW085115209A patent/TW541316B/zh active
- 1996-12-09 AR ARP960105567A patent/AR005245A1/es active IP Right Grant
- 1996-12-17 US US08/776,231 patent/US5965692A/en not_active Expired - Lifetime
- 1996-12-17 BR BR9612148A patent/BR9612148A/pt active Search and Examination
- 1996-12-17 WO PCT/SE1996/001680 patent/WO1997023499A1/fr not_active Ceased
- 1996-12-17 ES ES99120315T patent/ES2163916T3/es not_active Expired - Lifetime
- 1996-12-17 NZ NZ324902A patent/NZ324902A/en not_active IP Right Cessation
- 1996-12-17 DK DK99120315T patent/DK0995755T3/da active
- 1996-12-17 KR KR10-1998-0704728A patent/KR100458545B1/ko not_active Expired - Fee Related
- 1996-12-17 CA CA002238737A patent/CA2238737A1/fr not_active Abandoned
- 1996-12-17 EP EP96943446A patent/EP0869966B1/fr not_active Expired - Lifetime
- 1996-12-17 JP JP9523571A patent/JP2000504313A/ja active Pending
- 1996-12-17 SI SI9630712T patent/SI0869966T1/xx unknown
- 1996-12-17 DE DE69634492T patent/DE69634492T2/de not_active Expired - Lifetime
- 1996-12-17 PT PT99120315T patent/PT995755E/pt unknown
- 1996-12-17 ES ES96943446T patent/ES2128283T3/es not_active Expired - Lifetime
- 1996-12-17 SI SI9630364T patent/SI0995755T1/xx unknown
- 1996-12-17 AT AT99120315T patent/ATE204292T1/de active
- 1996-12-17 DE DE122004000046C patent/DE122004000046I2/de active Active
- 1996-12-17 PL PL96327569A patent/PL187468B1/pl not_active IP Right Cessation
- 1996-12-17 IL IL12485796A patent/IL124857A0/xx unknown
- 1996-12-17 TR TR1998/01151T patent/TR199801151T2/xx unknown
- 1996-12-17 EE EE9800187A patent/EE04022B1/xx not_active IP Right Cessation
- 1996-12-17 DE DE69614579T patent/DE69614579T2/de not_active Expired - Lifetime
- 1996-12-17 DK DK96943446T patent/DK0869966T3/da active
- 1996-12-17 EP EP05000116A patent/EP1533318A1/fr not_active Withdrawn
- 1996-12-17 SK SK821-98A patent/SK285588B6/sk not_active IP Right Cessation
- 1996-12-17 HU HU9900115A patent/HUP9900115A3/hu unknown
- 1996-12-17 AT AT96943446T patent/ATE291031T1/de active
- 1996-12-17 NZ NZ504245A patent/NZ504245A/en not_active IP Right Cessation
- 1996-12-17 RU RU98111148/04A patent/RU2176644C2/ru not_active IP Right Cessation
- 1996-12-17 EP EP99120315A patent/EP0995755B1/fr not_active Expired - Lifetime
- 1996-12-19 MY MYPI96005362A patent/MY121222A/en unknown
1998
- 1998-05-26 IS IS4756A patent/IS1836B/is unknown
- 1998-06-09 MX MX9804623A patent/MX9804623A/es not_active IP Right Cessation
- 1998-06-18 NO NO982809A patent/NO982809L/no not_active Application Discontinuation
1999
- 1999-07-15 US US09/353,644 patent/US6262028B1/en not_active Expired - Fee Related
2002
- 2002-02-14 US US10/074,008 patent/US20020142968A1/en not_active Abandoned
2004
- 2004-02-12 US US10/776,245 patent/US7354905B2/en not_active Expired - Fee Related
2005
- 2005-03-03 NL NL300179C patent/NL300179I2/nl unknown
- 2005-05-11 LU LU91172C patent/LU91172I2/fr unknown

Also Published As

Publication number	Publication date
RU2176644C2 (ru)	2001-12-10
MX9804623A (es)	1998-10-31
EP0995755B1 (fr)	2001-08-16
TWI238827B (en)	2005-09-01
DE122004000046I1 (de)	2005-04-21
AR005245A1 (es)	1999-04-28
HUP9900115A3 (en)	1999-11-29
DK0995755T3 (da)	2001-11-12
EP1533318A1 (fr)	2005-05-25
SK82198A3 (en)	1998-12-02
HUP9900115A2 (hu)	1999-05-28
EP0869966B1 (fr)	2005-03-16
TR199801151T2 (xx)	1998-08-21
US20040162410A1 (en)	2004-08-19
US20020142968A1 (en)	2002-10-03
KR19990076624A (ko)	1999-10-15
NL300179I1 (nl)	2005-05-02
US5965692A (en)	1999-10-12
EE9800187A (et)	1998-12-15
IL124857A0 (en)	1999-01-26
ES2128283T1 (es)	1999-05-16
ATE291031T1 (de)	2005-04-15
LU91172I2 (fr)	2005-07-11
PL327569A1 (en)	1998-12-21
DE122004000046I2 (de)	2011-06-16
WO1997023499A1 (fr)	1997-07-03
NO982809L (no)	1998-08-20
KR100458545B1 (ko)	2005-01-15
PL187468B1 (pl)	2004-07-30
EP0995755A1 (fr)	2000-04-26
IS4756A (is)	1998-05-26
DE69614579D1 (de)	2001-09-20
EE04022B1 (et)	2003-04-15
HK1026214A1 (en)	2000-12-08
ES2163916T3 (es)	2002-02-01
IS1836B (is)	2002-11-25
SI0995755T1 (en)	2002-02-28
JP2000504313A (ja)	2000-04-11
TW541316B (en)	2003-07-11
HK1016610A1 (en)	1999-11-05
SI0869966T1 (en)	2005-08-31
AU1217897A (en)	1997-07-17
AU706350B2 (en)	1999-06-17
NZ504245A (en)	2004-11-26
DE69614579T2 (de)	2002-06-27
PT995755E (pt)	2002-02-28
NO982809D0 (no)	1998-06-18
MY121222A (en)	2006-01-28
CA2238737A1 (fr)	1997-07-03
NL300179I2 (nl)	2005-06-01
DK0869966T3 (da)	2005-06-20
DE69634492T2 (de)	2006-04-13
ES2128283T3 (es)	2005-09-01
US6262028B1 (en)	2001-07-17
ATE204292T1 (de)	2001-09-15
DE69634492D1 (de)	2005-04-21
NZ324902A (en)	2000-06-23
EP0869966A1 (fr)	1998-10-14
BR9612148A (pt)	1999-07-13
US7354905B2 (en)	2008-04-08

Legal Events

Date	Code	Title	Description
2012-09-03	MM4A	Patent lapsed due to non-payment of maintenance fees	Effective date: 20111217

Publication	Publication Date	Title
SK285588B6 (sk)	2007-04-05	Prekurzory inhibítorov trombínu, spôsob ich prípravy, farmaceutický prostriedok s ich obsahom a ichpoužitie
EP0910573B1 (fr)	2003-01-29	Nouveaux derives d'acides amines et leur utilisation en tant qu'inhibiteurs de la trombine
SK6992000A3 (en)	2001-02-12	Compounds useful as competitive inhibitors of trypsin-like serine proteases, method for the preparation thereof, pharmaceutical compositions containing same and their use
EP0518675A2 (fr)	1992-12-16	Inhibiteurs cycliques de la rénine
CA2070983A1 (fr)	1992-12-12	Inhibiteurs cycliques de la renine
JP3580535B2 (ja)	2004-10-27	トロンビン阻害剤のプロドラッグ
AU706350C (en)	2000-03-09	Prodrugs of thrombin inhibitors
HK1026214B (en)	2002-08-09	Prodrugs of thrombin inhibitors
HK1075257A (en)	2005-12-09	Prodrugs of thrombin inhibitors
HK1016610B (en)	2005-06-10	Prodrugs of thrombin inhibitors
SA96170499B1 (ar)	2006-03-15	عقاقير اولية لكبح الثرومبين Prodrugs of thrombine inhibitors
EP0431972A2 (fr)	1991-06-12	Lactones macrocycliques possédant des propriétés d'inhibition de la rénine