JP2002533452A - プロテアーゼ阻害剤 - Google Patents
プロテアーゼ阻害剤Info
- Publication number
- JP2002533452A JP2002533452A JP2000591026A JP2000591026A JP2002533452A JP 2002533452 A JP2002533452 A JP 2002533452A JP 2000591026 A JP2000591026 A JP 2000591026A JP 2000591026 A JP2000591026 A JP 2000591026A JP 2002533452 A JP2002533452 A JP 2002533452A
- Authority
- JP
- Japan
- Prior art keywords
- alkyl
- group
- amino
- azocine
- disease
- 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- Withdrawn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
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title description 6
- 229940124158 Protease/peptidase inhibitor Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 130
- 238000000034 method Methods 0.000 claims abstract description 59
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 39
- 201000010099 disease Diseases 0.000 claims abstract description 36
- 108090000625 Cathepsin K Proteins 0.000 claims abstract description 27
- 239000004365 Protease Substances 0.000 claims abstract description 21
- 102000035195 Peptidases Human genes 0.000 claims abstract description 19
- 108091005804 Peptidases Proteins 0.000 claims abstract description 19
- 239000011159 matrix material Substances 0.000 claims abstract description 17
- 210000000845 cartilage Anatomy 0.000 claims abstract description 15
- 206010065687 Bone loss Diseases 0.000 claims abstract description 12
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 10
- 230000007850 degeneration Effects 0.000 claims abstract description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 9
- 208000007565 gingivitis Diseases 0.000 claims abstract description 8
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 8
- 201000001245 periodontitis Diseases 0.000 claims abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 8
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 7
- 150000004677 hydrates Chemical class 0.000 claims abstract description 3
- 239000012453 solvate Substances 0.000 claims abstract description 3
- 102000004171 Cathepsin K Human genes 0.000 claims abstract 3
- -1 2-benzofuranyl Chemical group 0.000 claims description 77
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- 102000005927 Cysteine Proteases Human genes 0.000 claims description 43
- 108010005843 Cysteine Proteases Proteins 0.000 claims description 43
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 19
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 18
- 229910052799 carbon Inorganic materials 0.000 claims description 15
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 claims description 14
- 102000012479 Serine Proteases Human genes 0.000 claims description 12
- 108010022999 Serine Proteases Proteins 0.000 claims description 12
- 125000006268 biphenyl-3-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C([H])C(*)=C([H])C([H])=C1[H] 0.000 claims description 12
- 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- 230000005764 inhibitory process Effects 0.000 claims description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 9
- 230000002401 inhibitory effect Effects 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 7
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
- 239000003085 diluting agent Substances 0.000 claims description 6
- 239000003937 drug carrier Substances 0.000 claims description 5
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 229910052717 sulfur Inorganic materials 0.000 claims description 5
- 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 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 4
- 229910052760 oxygen Inorganic materials 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical group C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 claims description 3
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 1
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- 239000011541 reaction mixture Substances 0.000 description 51
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
- 239000000243 solution Substances 0.000 description 30
- 102100024940 Cathepsin K Human genes 0.000 description 27
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 24
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 23
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
- 239000003112 inhibitor Substances 0.000 description 22
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- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
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- NKLCNNUWBJBICK-UHFFFAOYSA-N dess–martin periodinane Chemical compound C1=CC=C2I(OC(=O)C)(OC(C)=O)(OC(C)=O)OC(=O)C2=C1 NKLCNNUWBJBICK-UHFFFAOYSA-N 0.000 description 16
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- 239000012267 brine Substances 0.000 description 15
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 11
- 235000019341 magnesium sulphate Nutrition 0.000 description 11
- OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
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- 238000002360 preparation method Methods 0.000 description 9
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- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 8
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- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
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- XXRGLCKZBCIEKO-DLMDZQPMSA-N azocine Chemical compound C/1=C/C=C\N=C/C=C\1 XXRGLCKZBCIEKO-DLMDZQPMSA-N 0.000 description 7
- 238000010168 coupling process Methods 0.000 description 7
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- PNPBGYBHLCEVMK-UHFFFAOYSA-N benzylidene(dichloro)ruthenium;tricyclohexylphosphanium Chemical compound Cl[Ru](Cl)=CC1=CC=CC=C1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1.C1CCCCC1[PH+](C1CCCCC1)C1CCCCC1 PNPBGYBHLCEVMK-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/04—Drugs for skeletal disorders for non-specific disorders of the connective tissue
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D225/00—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom
- C07D225/02—Heterocyclic compounds containing rings of more than seven members having one nitrogen atom as the only ring hetero atom not condensed with other rings
Landscapes
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Physical Education & Sports Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Immunology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Peptides Or Proteins (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US11414398P | 1998-12-23 | 1998-12-23 | |
| US60/114,143 | 1998-12-23 | ||
| PCT/US1999/030602 WO2000039115A1 (fr) | 1998-12-23 | 1999-12-21 | Inhibiteurs de proteases |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2002533452A true JP2002533452A (ja) | 2002-10-08 |
Family
ID=22353596
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2000591026A Withdrawn JP2002533452A (ja) | 1998-12-23 | 1999-12-21 | プロテアーゼ阻害剤 |
Country Status (9)
| Country | Link |
|---|---|
| EP (1) | EP1140897A4 (fr) |
| JP (1) | JP2002533452A (fr) |
| AR (1) | AR021970A1 (fr) |
| AU (1) | AU2713100A (fr) |
| CO (1) | CO5180541A1 (fr) |
| DZ (1) | DZ2976A1 (fr) |
| HK (1) | HK1041690A1 (fr) |
| PE (1) | PE20001355A1 (fr) |
| WO (1) | WO2000039115A1 (fr) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008512461A (ja) * | 2004-09-07 | 2008-04-24 | スミスクライン・ビーチャム・コーポレイション | 新規化合物 |
| JP2008526982A (ja) * | 2005-01-13 | 2008-07-24 | ブリストル−マイヤーズ スクイブ カンパニー | Ｘｉａ因子阻害剤としての置換ビアリール化合物 |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20030144175A1 (en) | 1998-12-23 | 2003-07-31 | Smithkline Beecham Corporation | Protease inhibitors |
| WO2001034599A1 (fr) | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Inhibiteurs de protease |
| EP1229914A4 (fr) | 1999-11-10 | 2004-06-23 | Smithkline Beecham Corp | Inhibiteurs de protease |
| WO2001034600A1 (fr) | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Inhibiteurs de protease |
| NZ520588A (en) | 2000-03-21 | 2004-06-25 | Smithkline Beecham Corp | Protease inhibitors |
| US6982263B2 (en) | 2001-06-08 | 2006-01-03 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nitriles useful as reversible inhibitors of cysteine proteases |
| WO2003075853A2 (fr) | 2002-03-08 | 2003-09-18 | Bristol-Myers Squibb Company | Derives cycliques servant de modulateurs de l'activite du recepteur de la chimiokine |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DZ2285A1 (fr) * | 1996-08-08 | 2002-12-25 | Smithkline Beecham Corp | Inhibiteurs de protéase de la cystéine. |
| US6369077B1 (en) * | 1997-05-08 | 2002-04-09 | Smithkline Beecham Corporation | Protease inhibitors |
-
1999
- 1999-12-16 CO CO99078651A patent/CO5180541A1/es not_active Application Discontinuation
- 1999-12-21 AU AU27131/00A patent/AU2713100A/en not_active Abandoned
- 1999-12-21 JP JP2000591026A patent/JP2002533452A/ja not_active Withdrawn
- 1999-12-21 WO PCT/US1999/030602 patent/WO2000039115A1/fr not_active Application Discontinuation
- 1999-12-21 EP EP99968936A patent/EP1140897A4/fr not_active Withdrawn
- 1999-12-21 AR ARP990106647A patent/AR021970A1/es unknown
- 1999-12-22 DZ DZ990276A patent/DZ2976A1/fr active
- 1999-12-23 PE PE1999001311A patent/PE20001355A1/es not_active Application Discontinuation
-
2002
- 2002-02-19 HK HK02101209.3A patent/HK1041690A1/zh unknown
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2008512461A (ja) * | 2004-09-07 | 2008-04-24 | スミスクライン・ビーチャム・コーポレイション | 新規化合物 |
| JP2008526982A (ja) * | 2005-01-13 | 2008-07-24 | ブリストル−マイヤーズ スクイブ カンパニー | Ｘｉａ因子阻害剤としての置換ビアリール化合物 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1140897A1 (fr) | 2001-10-10 |
| HK1041690A1 (zh) | 2002-07-19 |
| AR021970A1 (es) | 2002-09-04 |
| PE20001355A1 (es) | 2001-01-28 |
| WO2000039115A1 (fr) | 2000-07-06 |
| EP1140897A4 (fr) | 2002-04-03 |
| CO5180541A1 (es) | 2002-07-30 |
| DZ2976A1 (fr) | 2004-03-15 |
| AU2713100A (en) | 2000-07-31 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| A300 | Application deemed to be withdrawn because no request for examination was validly filed |
Free format text: JAPANESE INTERMEDIATE CODE: A300 Effective date: 20070306 |