EP0954526A2 - Serine protease inhibitors - Google Patents
Serine protease inhibitorsInfo
- Publication number
- EP0954526A2 EP0954526A2 EP97952232A EP97952232A EP0954526A2 EP 0954526 A2 EP0954526 A2 EP 0954526A2 EP 97952232 A EP97952232 A EP 97952232A EP 97952232 A EP97952232 A EP 97952232A EP 0954526 A2 EP0954526 A2 EP 0954526A2
- Authority
- EP
- European Patent Office
- Prior art keywords
- compound
- alkyl
- aryl
- carbonyl
- oxadiazolyl
- Prior art date
- Legal status (The legal status 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 status listed.)
- Withdrawn
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- C07K5/0202—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing at least one abnormal peptide link containing the structure -NH-X-X-C(=0)-, X being an optionally substituted carbon atom or a heteroatom, e.g. beta-amino acids
-
- 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
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06026—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atom, i.e. Gly or Ala
-
- 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
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06043—Leu-amino acid
-
- 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
- C07K5/06017—Dipeptides with the first amino acid being neutral and aliphatic
- C07K5/06034—Dipeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms
- C07K5/06052—Val-amino acid
-
- 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
-
- 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
- C07K5/06086—Dipeptides with the first amino acid being basic
-
- 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
- C07K5/06104—Dipeptides with the first amino acid being acidic
-
- 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
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
-
- 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
- C07K5/06139—Dipeptides with the first amino acid being heterocyclic
- C07K5/06156—Dipeptides with the first amino acid being heterocyclic and Trp-amino acid; Derivatives thereof
-
- 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
- C07K5/06191—Dipeptides containing heteroatoms different from O, S, or N
-
- 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
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0806—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 0 or 1 carbon atoms, i.e. Gly, Ala
-
- 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
- C07K5/12—Cyclic peptides with only normal peptide bonds in the ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Definitions
- the benzene ring is substituted with an alkyl, such as methyl; with a haloalkyl, such as trifluoromethyl; or with a dialkylamino, preferably dimethylamin ⁇ .
- R is a fused arylalkyl group such as methylenenaphthyl; or a fused aryl-cycloalkyl or alkyl fused aryl-cycloalkyl such as 3, 4-methylenedioxy benzyl.
- W is O or S; or C or N optionally substituted with H, alkyl or aryl.
- X is N and Y is O.
- X is O and Y is N.
- R 13 is an optionally substituted phenyl or benzyl; pyridyl, piperidinyl, alkyl or H or a fused ring system such as 3,4-methylenedioxybenzyl; R 14 is optionally substituted amino or an arylalkyloxycarboxamide such as benzyloxycarboxamide; and R 15 is H or halo.
- R 2 is isopropyl and R 3 is H.
- the present invention additionally provides compounds of the formula (Group V):
- X is N and Y is O. In another preferred embodiment, X is O and Y is N.
- the invention further provides compounds of the formula (Group VI):
- R is alkyl or alkenyl optionally substituted with 1-3 halo or hydroxyl; -alkyl- C(O)OCH 3 ; alkylamino, dialkylamino, alkyldialkylamino; or cycloalkyl, alkylcycloalkyl, alkenylcycloalkyl, (C 5 -C 12 )aryl, (C 5 -C 12 )arylalkyl, (C 5 - C 12 )arylalkenyl, fused (C 5 -C 12 )aryl-cycloalkyl or fused (C 5 -C 12 )aryl-cyclalkylalkyl optionally comprising 1-4 heteroatoms selected from N, O and S, and optionally substituted with halo, cyano, nitro, hydroxyl, haloalkyl, amino, aminoalkyl, dialkylamino, alkyl, alkenyl, alkylenedioxy, alkynyl, alk
- X and Y are independently O, S or N, wherein N is optionally substituted with alkyl or alkenyl optionally substituted with 1-3 halo atoms; (C 5 -C 6 )aryl, arylalkyl or arylalkenyl optionally comprising 1-3 heteroatoms selected from N, O and S, and optionally substituted with halo, cyano, nitro, hydroxyl, haloalkyl, amino, aminoalkyl, dialkylamino, alkyl, alkenyl, alkynyl, alkoxy, haloalkoxy, carboxyl, carboalkoxy, alkylcarboxamide, arylcarboxamide, alkylthio or haloalkylthio; and
- the protecting group [PGR,] is removed from alcohol (D) by reacting the aldehyde of formula (C) with hydrochloric acid in dioxane.
- the protecting group [PGr t ] may be any suitable group, preferably Boc.
- R ⁇ , R 12 and E together form a monocyclic or bicyclic ring comprising 5-10
- Figure 34 shows the activity of certain compounds of Group V.
- CE-2158 3-(S)-[(Benzyloxycarbonyl)amino-(5,6 phenyl- ⁇ -lactam]-N-[l-(3-[5-
- CE-2244 2-Oxo-5-methyl-l,4-(l-thiophenodiazepine)-N-[l-(2-[5-(3- methylbenzyl)-l,3,4-oxadiazolyl]carbonyl)-2-(S)-methylpropyl]acetamide
- CE-2245 2-Oxo-5-methyl- 1 ,4-(2-phenyl- 1 -thiophenodiazepine)-N-[ 1 -(2-[5-(3- methylbenzyl)-l,3,4-oxadiazolyl]carbonyl)-2-(S)-methylpropyl]acetamide
- CE-2246 4-(R)-(2-Isobutyl)-2,5-imidazolidinedione-N-[l-(2-[5-(3- methylbenzyl)-l,3,4-oxadiazolyl]carbonyl)-2-(S)-methylpropyl]acetamide
- CE-2247 4-( ⁇
- ONO-PO-717 2-Oxo-5-(4-chlorophenyl)-l,4-benzodiazepine-N-[l-(2-[5-tert- butyl-l,3 5 4-oxadiazolyl]carbonyl)-2-(S)-methylpropyl]acetamide
- ONO-PO-718 2-[5-Amino-6-oxo-2-(4-fluorophenyl)- 1 ,6-dihydro- 1 - pyrimidinyl]-N-[l-(2-[5-(tert-butyl)-l,3,4-oxadiazolyl]carbonyl)-2-(R)- methylpropyl] acetamide
- Example 10 (CE-2054)(Benzyloxycarbonyl)-I-valyl-N-[l-(3-[5-(3,5- ditrifluoromethylbenzyl)- 1 ,2,4-oxadiazolyl] carbonyl)-2-(S)-methylpropyl]-Z,- prolinamide. Prepared similar to Example 1 of WO 96/16080. FAB MS [M+H] m/z; Calcd: 726, Found: 726.
- Example 14 (CE-2062)(Benzyloxycarbonyl)-I-valyl-N-[l-(3-[5-(3-phenylbenzyl)- 1,2,4-oxadiazolyl] carbonyl)-2-( ⁇ S)-methylpropyl]-E-prolinamide. Prepared similar to Example 1 of WO 96/16080. FAB MS [M+H] m/z; Calcd: 666, Found: 666.
- Example 107 2-[5-Amino-6-oxo-2-(3-pyridyl)-l,6-dihydro-l- pyrirnidmyl]-N-[l-(2-[5-( ⁇ , ⁇ -dimethylbenzyl)-l,3,4-oxadiazolyl]carbonyl)-2-(S)- methylpropyl]acetamide was prepared in a similar manner to Example 91.
- Example 110 2-[5-Amino-6-oxo-2-phenyl-l,6-dihydro-l- pyrimidinyl]-N-[l-(2-[5-(l-methylcyclopropyl)-l,3,4-oxadiazolyl]carbonyl)-2-(S)- methylpropyl]acetamide was prepared in a similar manner to Example 91.
- Optical density (SPECTRA MAX 250, Molecular Devices) at 405 nm due to p-nitroaniline generated by the enzyme reaction was measured at 37°C in order to measure the reaction rate during the period that the production rate of p-nitroaniline remains linear.
- the rate, mO.D./min. was measured for 10 minutes at 30 second intervals immediately after the addition of the enzyme solution.
- IC 50 values were determined by log-logit method and converted to K ⁇ values by Dixson plot method. The values are presented in Table 1 below.
- the inhibitors were dissolved or suspended in polyethylene glycol (PEG), PEG-400 or PEG:H 2 O:EtOH at a concentration of 10 mg/ml.
- PEG polyethylene glycol
- PEG-400 PEG:H 2 O:EtOH
- Rats received 10 mg inhibitor/kg body weight in a volume of 1 ml/kg.
- the rats were killed with an overdose of urethane (2.5 g/kg; i.p.) and the blood collected in a heparinized tube via cardiac puncture. Red blood cells were separated from the plasma by centrifugation.
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Chemical & Material Sciences (AREA)
- Crystallography & Structural Chemistry (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Enzymes And Modification Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (21)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US771317 | 1985-08-30 | ||
US760916 | 1991-09-17 | ||
US761190 | 1991-09-18 | ||
US761313 | 1996-12-06 | ||
US08/761,190 US5807829A (en) | 1994-11-21 | 1996-12-06 | Serine protease inhibitor--tripeptoid analogs |
US08/771,317 US5801148A (en) | 1994-11-21 | 1996-12-06 | Serine protease inhibitors-proline analogs |
US762381 | 1996-12-06 | ||
US08/760,916 US5861380A (en) | 1994-11-21 | 1996-12-06 | Serine protease inhibitors-keto and di-keto containing ring systems |
US08/762,381 US5891852A (en) | 1994-11-21 | 1996-12-06 | Serine protease inhibitors-cycloheptane derivatives |
US08/761,313 US5869455A (en) | 1994-11-21 | 1996-12-06 | Serine protease inhibitors-N-substituted derivatives |
US98529897A | 1997-12-04 | 1997-12-04 | |
US984884 | 1997-12-04 | ||
US984881 | 1997-12-04 | ||
US985056 | 1997-12-04 | ||
US985298 | 1997-12-04 | ||
US08/984,881 US6015791A (en) | 1994-11-21 | 1997-12-04 | Serine protease inhibitors-cycloheptane derivatives |
US08/984,884 US6001811A (en) | 1994-11-21 | 1997-12-04 | Serine protease inhibitors--N-substituted derivatives |
US08/985,201 US6150334A (en) | 1994-11-21 | 1997-12-04 | Serine protease inhibitors-tripeptoid analogs |
US985201 | 1997-12-04 | ||
US08/985,056 US5998379A (en) | 1994-11-21 | 1997-12-04 | Serine protease inhibitors-proline analogs |
PCT/US1997/021636 WO1998024806A2 (en) | 1996-12-06 | 1997-12-05 | Substituted oxadiazole, thiadiazole and triazole serine protease inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
EP0954526A2 true EP0954526A2 (en) | 1999-11-10 |
Family
ID=27581319
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP97952232A Withdrawn EP0954526A2 (en) | 1996-12-06 | 1997-12-05 | Serine protease inhibitors |
Country Status (11)
Country | Link |
---|---|
EP (1) | EP0954526A2 (zh) |
JP (1) | JP3220169B2 (zh) |
CN (1) | CN1247542A (zh) |
AU (1) | AU734615B2 (zh) |
CA (1) | CA2272548A1 (zh) |
HU (1) | HUP0100669A3 (zh) |
NO (1) | NO992734L (zh) |
NZ (1) | NZ336046A (zh) |
RU (1) | RU2217436C2 (zh) |
TR (2) | TR200103270T2 (zh) |
WO (1) | WO1998024806A2 (zh) |
Families Citing this family (34)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6004933A (en) * | 1997-04-25 | 1999-12-21 | Cortech Inc. | Cysteine protease inhibitors |
US6656910B2 (en) * | 1997-12-04 | 2003-12-02 | Cortech, Inc. | Serine protease inhibitors |
EP1089752A4 (en) * | 1998-06-03 | 2002-01-02 | Cortech Inc | ALPHA-KETO OXADIAZOLE AS A SERINE PROTEASE INHIBITOR |
AU9031598A (en) * | 1998-08-17 | 2000-03-06 | Cortech, Inc. | Serine protease inhibitors comprising alpha-keto heterocycles |
FR2782997A1 (fr) * | 1998-09-08 | 2000-03-10 | Hoechst Marion Roussel Inc | Nouveaux derives de la benzodiazepinone, procede de preparation et intermediaires de ce procede, application a titre de medicaments et compositions pharmaceutiques les renfermant |
WO2000052034A2 (en) * | 1999-03-05 | 2000-09-08 | The Trustees Of University Technology Corporation | Inhibitors of serine protease activity, methods and compositions for treatment of viral infections |
WO2000051624A2 (en) * | 1999-03-05 | 2000-09-08 | The Trustees Of University Technology Corporation | Methods and compositions useful in inhibiting apoptosis |
WO2000051625A1 (en) * | 1999-03-05 | 2000-09-08 | The Trustees Of University Technology Corporation | Inhibitors of serine protease activity, methods and compositions for treatment of herpes viruses |
US6489308B1 (en) * | 1999-03-05 | 2002-12-03 | Trustees Of University Of Technology Corporation | Inhibitors of serine protease activity, methods and compositions for treatment of nitric-oxide-induced clinical conditions |
HUP0200476A3 (en) * | 1999-03-12 | 2004-03-29 | Ono Pharmaceutical Co | 1,3,4-oxadiazole derivatives and process for producing the same |
US6569876B1 (en) | 1999-06-17 | 2003-05-27 | John C. Cheronis | Method and structure for inhibiting activity of serine elastases |
US7122627B2 (en) | 1999-07-26 | 2006-10-17 | Bristol-Myers Squibb Company | Lactam inhibitors of Hepatitis C virus NS3 protease |
WO2001007407A1 (en) * | 1999-07-26 | 2001-02-01 | Bristol-Myers Squibb Pharma Company | Lactam inhibitors of hepatitis c virus ns3 protease |
AU7444600A (en) * | 1999-09-27 | 2001-04-30 | Ono Pharmaceutical Co. Ltd. | Pyrimidine derivatives, process for preparing the derivatives and drugs containing the same as the active ingredient |
US6797720B2 (en) | 1999-12-03 | 2004-09-28 | Ono Pharmaceutical Co., Ltd. | 1,3,4-oxadiazoline derivative and an agent comprising its derivative as active ingredient |
AU1556601A (en) * | 1999-12-03 | 2001-06-12 | Ono Pharmaceutical Co. Ltd. | 1,3,4-oxadiazolin-2-one derivatives and drugs containing these derivatives as the active ingredient |
KR20020072303A (ko) * | 2000-02-03 | 2002-09-14 | 오노 야꾸힝 고교 가부시키가이샤 | 1,3,4-옥사디아졸 유도체 및 그 제조 방법 |
WO2001057005A1 (fr) * | 2000-02-03 | 2001-08-09 | Ono Pharmaceutical Co., Ltd. | Derives de 1,3,4-oxadiazole et leur procede de production |
AU2001277736A1 (en) * | 2000-08-10 | 2002-02-25 | Ono Pharmaceutical Co. Ltd. | 2-(5-amino-6-oxo-2-phenyl-1,6-dihydro-1-pyrimidyl)-n-(1-(2-( -t-butyl-1,3,4-oxadiazolyl)carbonyl)-2-(r,s)-methylpropyl) acetamide hydrochloride |
US20040023998A1 (en) * | 2000-09-08 | 2004-02-05 | Tsutomu Kojima | Novel crystals of 1,3,4-oxadiazole derivatives, process for producing the crystals and medicines containing the same as the active ingredient |
KR20030046470A (ko) * | 2000-09-29 | 2003-06-12 | 오노 야꾸힝 고교 가부시키가이샤 | 기도 점액 분비 억제제 |
WO2003006014A1 (en) * | 2001-07-10 | 2003-01-23 | Ono Pharmaceutical Co., Ltd. | Medicine comprising combination of five-membered heterocyclic compound and drug compensating for or enhancing its activity |
EP1404704B9 (en) * | 2001-07-11 | 2008-02-20 | Vertex Pharmaceuticals Incorporated | Bridged bicyclic serine protease inhibitors |
IL148924A (en) * | 2002-03-26 | 2015-06-30 | Mor Research Applic Ltd | Use of substances that inhibit intracellular elastase activity in the preparation of a drug for the treatment and / or prevention of necrosis of cells and related diseases |
PL2520654T3 (pl) | 2003-08-26 | 2017-08-31 | The Regents Of The University Of Colorado, A Body Corporate | Inhibitory aktywności proteazy serynowej i ich zastosowanie w sposobach i kompozycjach do leczenia zakażeń bakteryjnych |
US7358368B2 (en) | 2003-11-04 | 2008-04-15 | Ajinomoto Co., Inc. | Azlactone compound and method for preparation thereof |
CA2651762A1 (en) | 2006-05-23 | 2007-11-29 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
TWI389899B (zh) * | 2006-08-08 | 2013-03-21 | Msd Oss Bv | 具口服活性之凝血酶抑制劑 |
US8293915B2 (en) | 2007-02-09 | 2012-10-23 | Irm Llc | Compounds and compositions as channel activating protease inhibitors |
EP2152674B1 (en) | 2007-05-22 | 2011-08-03 | Boehringer Ingelheim International GmbH | Benzimidazolone chymase inhibitors |
CA2839917A1 (en) | 2011-06-24 | 2012-12-27 | The Regents Of The University Of Colorado, A Body Corporate | Compositions, methods and uses for alpha-1 antitrypsin fusion molecules |
AU2013202648B2 (en) | 2012-01-10 | 2016-05-19 | Konkuk University | Compositions, methods and uses for alpha-1 antitrypsin fusion molecules |
CN105263901B (zh) * | 2013-05-08 | 2017-06-23 | 橘生药品工业株式会社 | α‑取代甘氨酰胺衍生物 |
WO2016020836A1 (en) * | 2014-08-06 | 2016-02-11 | Novartis Ag | Quinolone derivatives as antibacterials |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB9216272D0 (en) * | 1991-08-15 | 1992-09-09 | Ici Plc | Substituted heterocycles |
GB9307555D0 (en) * | 1992-04-16 | 1993-06-02 | Zeneca Ltd | Heterocyclic compounds |
FR2694295B1 (fr) * | 1992-07-28 | 1994-09-02 | Adir | Nouveaux peptides dérivés de trifluoromethylcetones, leur procéde de préparation et les compositions pharmaceutiques qui les contiennent. |
JP3721538B2 (ja) * | 1994-06-02 | 2005-11-30 | メレル ファーマスーティカルズ インコーポレイテッド | エラスターゼのパーフルオロアルキルケトン阻害剤およびそれらを製造する方法 |
US5618792A (en) * | 1994-11-21 | 1997-04-08 | Cortech, Inc. | Substituted heterocyclic compounds useful as inhibitors of (serine proteases) human neutrophil elastase |
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1997
- 1997-12-05 JP JP52565698A patent/JP3220169B2/ja not_active Expired - Fee Related
- 1997-12-05 HU HU0100669A patent/HUP0100669A3/hu unknown
- 1997-12-05 NZ NZ336046A patent/NZ336046A/xx unknown
- 1997-12-05 AU AU55894/98A patent/AU734615B2/en not_active Ceased
- 1997-12-05 CN CN97180392A patent/CN1247542A/zh active Pending
- 1997-12-05 TR TR2001/03270T patent/TR200103270T2/xx unknown
- 1997-12-05 TR TR1999/01681T patent/TR199901681T2/xx unknown
- 1997-12-05 CA CA002272548A patent/CA2272548A1/en not_active Abandoned
- 1997-12-05 RU RU99114606/04A patent/RU2217436C2/ru not_active IP Right Cessation
- 1997-12-05 EP EP97952232A patent/EP0954526A2/en not_active Withdrawn
- 1997-12-05 WO PCT/US1997/021636 patent/WO1998024806A2/en not_active Application Discontinuation
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1999
- 1999-06-04 NO NO992734A patent/NO992734L/no not_active Application Discontinuation
Non-Patent Citations (1)
Title |
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See references of WO9824806A2 * |
Also Published As
Publication number | Publication date |
---|---|
NZ336046A (en) | 2000-10-27 |
WO1998024806A3 (en) | 1998-10-15 |
NO992734L (no) | 1999-08-02 |
TR199901681T2 (xx) | 2000-03-21 |
JP2001507679A (ja) | 2001-06-12 |
JP3220169B2 (ja) | 2001-10-22 |
WO1998024806A2 (en) | 1998-06-11 |
CA2272548A1 (en) | 1998-06-11 |
HUP0100669A2 (hu) | 2001-08-28 |
NO992734D0 (no) | 1999-06-04 |
RU2217436C2 (ru) | 2003-11-27 |
CN1247542A (zh) | 2000-03-15 |
HUP0100669A3 (en) | 2001-12-28 |
WO1998024806B1 (en) | 1999-05-20 |
TR200103270T2 (tr) | 2003-03-21 |
AU5589498A (en) | 1998-06-29 |
AU734615B2 (en) | 2001-06-21 |
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