NO318910B1 - Proteaseinhibitorer, fremgangsmate for syntese og anvendelse derav samt farmasoytisk preparat - Google Patents
Proteaseinhibitorer, fremgangsmate for syntese og anvendelse derav samt farmasoytisk preparat Download PDFInfo
- Publication number
- NO318910B1 NO318910B1 NO20013124A NO20013124A NO318910B1 NO 318910 B1 NO318910 B1 NO 318910B1 NO 20013124 A NO20013124 A NO 20013124A NO 20013124 A NO20013124 A NO 20013124A NO 318910 B1 NO318910 B1 NO 318910B1
- Authority
- NO
- Norway
- Prior art keywords
- methyl
- carboxylic acid
- azepan
- amide
- butyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims abstract description 400
- 230000015572 biosynthetic process Effects 0.000 title claims description 10
- 238000003786 synthesis reaction Methods 0.000 title claims description 10
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title abstract description 8
- 239000000137 peptide hydrolase inhibitor Substances 0.000 title abstract description 8
- 239000008194 pharmaceutical composition Substances 0.000 title abstract 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 819
- 201000010099 disease Diseases 0.000 claims abstract description 31
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 31
- 108090000625 Cathepsin K Proteins 0.000 claims abstract description 24
- 239000004365 Protease Substances 0.000 claims abstract description 15
- 108091005804 Peptidases Proteins 0.000 claims abstract description 14
- 239000011159 matrix material Substances 0.000 claims abstract description 12
- 208000001132 Osteoporosis Diseases 0.000 claims abstract description 9
- 210000000845 cartilage Anatomy 0.000 claims abstract description 9
- 206010065687 Bone loss Diseases 0.000 claims abstract description 7
- 208000007565 gingivitis Diseases 0.000 claims abstract description 7
- 201000001245 periodontitis Diseases 0.000 claims abstract description 7
- 230000015556 catabolic process Effects 0.000 claims abstract description 6
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 6
- 201000008482 osteoarthritis Diseases 0.000 claims abstract description 6
- 206010039073 rheumatoid arthritis Diseases 0.000 claims abstract description 6
- 238000006731 degradation reaction Methods 0.000 claims abstract description 5
- 102000004171 Cathepsin K Human genes 0.000 claims abstract 2
- 238000002360 preparation method Methods 0.000 claims description 283
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 199
- 238000004128 high performance liquid chromatography Methods 0.000 claims description 181
- 239000000203 mixture Substances 0.000 claims description 99
- -1 N-methylindoyl Chemical group 0.000 claims description 75
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 65
- 102000005927 Cysteine Proteases Human genes 0.000 claims description 39
- 108010005843 Cysteine Proteases Proteins 0.000 claims description 39
- XZELWEMGWISCTP-UHFFFAOYSA-N 5-methoxy-1-benzofuran-2-carboxylic acid Chemical compound COC1=CC=C2OC(C(O)=O)=CC2=C1 XZELWEMGWISCTP-UHFFFAOYSA-N 0.000 claims description 37
- YMZTUCZCQMQFMK-UHFFFAOYSA-N 3-methyl-1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2C(C)=C(C(O)=O)OC2=C1 YMZTUCZCQMQFMK-UHFFFAOYSA-N 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 30
- UPUZGXILYFKSGE-UHFFFAOYSA-N quinoxaline-2-carboxylic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CN=C21 UPUZGXILYFKSGE-UHFFFAOYSA-N 0.000 claims description 26
- LOAUVZALPPNFOQ-UHFFFAOYSA-N quinaldic acid Chemical compound C1=CC=CC2=NC(C(=O)O)=CC=C21 LOAUVZALPPNFOQ-UHFFFAOYSA-N 0.000 claims description 24
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 22
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 15
- 229910052739 hydrogen Inorganic materials 0.000 claims description 15
- 239000007800 oxidant agent Substances 0.000 claims description 13
- 230000001590 oxidative effect Effects 0.000 claims description 13
- GVZXSZWCZGKLRS-UHFFFAOYSA-N thieno[3,2-b]thiophene-5-carboxylic acid Chemical compound S1C=CC2=C1C=C(C(=O)O)S2 GVZXSZWCZGKLRS-UHFFFAOYSA-N 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 11
- 102000012479 Serine Proteases Human genes 0.000 claims description 10
- 108010022999 Serine Proteases Proteins 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 239000003814 drug Substances 0.000 claims description 9
- UDYFLDICVHJSOY-UHFFFAOYSA-N sulfur trioxide-pyridine complex Substances O=S(=O)=O.C1=CC=NC=C1 UDYFLDICVHJSOY-UHFFFAOYSA-N 0.000 claims description 9
- 239000003795 chemical substances by application Substances 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- 229940079593 drug Drugs 0.000 claims description 7
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 7
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical group [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 claims description 6
- 239000000654 additive Substances 0.000 claims description 6
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 6
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- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 4
- 241000562429 Jamides Species 0.000 claims description 4
- 125000003545 alkoxy group Chemical group 0.000 claims description 4
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004802 cyanophenyl group Chemical group 0.000 claims description 4
- 239000003937 drug carrier Substances 0.000 claims description 4
- 229910052736 halogen Inorganic materials 0.000 claims description 4
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000005425 toluyl group Chemical group 0.000 claims description 4
- FSWZCXHBMVKFCV-GTPINHCMSA-N (2s)-2-amino-n-(1-benzoyl-3-hydroxyazepan-4-yl)-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1C(=O)C1=CC=CC=C1 FSWZCXHBMVKFCV-GTPINHCMSA-N 0.000 claims description 3
- RIQUIYQTTZIVIZ-AOCRQIFASA-N (2s)-2-amino-n-(1-benzyl-3-hydroxyazepan-4-yl)-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1CC1=CC=CC=C1 RIQUIYQTTZIVIZ-AOCRQIFASA-N 0.000 claims description 3
- QNQSYELXGHSKTE-GTPINHCMSA-N (2s)-2-amino-n-[1-(benzenesulfonyl)-3-hydroxyazepan-4-yl]-4-methylpentanamide Chemical compound C1C(O)C(NC(=O)[C@@H](N)CC(C)C)CCCN1S(=O)(=O)C1=CC=CC=C1 QNQSYELXGHSKTE-GTPINHCMSA-N 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 3
- 230000000996 additive effect Effects 0.000 claims description 3
- 150000002367 halogens Chemical class 0.000 claims description 3
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 3
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- PQSBQHKJPQBLRS-FHERZECASA-N (2s)-2-amino-n-[3-hydroxy-1-(4-methylpentanoyl)azepan-4-yl]-4-methylpentanamide Chemical compound CC(C)CCC(=O)N1CCCC(NC(=O)[C@@H](N)CC(C)C)C(O)C1 PQSBQHKJPQBLRS-FHERZECASA-N 0.000 claims description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
- ZAIRIKJXUIZRPN-ADKAHSJRSA-N benzyl n-[(2s)-1-[(3-hydroxyazepan-4-yl)amino]-4-methyl-1-oxopentan-2-yl]carbamate Chemical compound N([C@@H](CC(C)C)C(=O)NC1C(CNCCC1)O)C(=O)OCC1=CC=CC=C1 ZAIRIKJXUIZRPN-ADKAHSJRSA-N 0.000 claims description 2
- 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- 125000004262 quinoxalin-2-yl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N=C1* 0.000 claims description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims 1
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims 1
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims 1
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims 1
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims 1
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims 1
- 125000005843 halogen group Chemical group 0.000 claims 1
- 125000003037 imidazol-2-yl group Chemical group [H]N1C([*])=NC([H])=C1[H] 0.000 claims 1
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- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims 1
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- QTLLOLTVQMFWDZ-UHFFFAOYSA-N 4-aminoazepan-3-one Chemical compound NC1CCCNCC1=O QTLLOLTVQMFWDZ-UHFFFAOYSA-N 0.000 abstract description 3
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- 206010020584 Hypercalcaemia of malignancy Diseases 0.000 abstract 1
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- 150000004677 hydrates Chemical class 0.000 abstract 1
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- OFFSPAZVIVZPHU-UHFFFAOYSA-N 1-benzofuran-2-carboxylic acid Chemical compound C1=CC=C2OC(C(=O)O)=CC2=C1 OFFSPAZVIVZPHU-UHFFFAOYSA-N 0.000 description 396
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 313
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- 238000006467 substitution reaction Methods 0.000 description 237
- 239000000243 solution Substances 0.000 description 209
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 173
- 239000007787 solid Substances 0.000 description 162
- 238000005481 NMR spectroscopy Methods 0.000 description 131
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- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 85
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
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- 238000006243 chemical reaction Methods 0.000 description 36
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 33
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- 239000012044 organic layer Substances 0.000 description 31
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- 238000004458 analytical method Methods 0.000 description 28
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 28
- 239000011734 sodium Substances 0.000 description 28
- 238000003756 stirring Methods 0.000 description 28
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- VNNLHYZDXIBHKZ-UHFFFAOYSA-N thiophene-2-sulfonyl chloride Chemical group ClS(=O)(=O)C1=CC=CS1 VNNLHYZDXIBHKZ-UHFFFAOYSA-N 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/14—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing three or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
- A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
-
- 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
- A61P19/08—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]
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- A—HUMAN NECESSITIES
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- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
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- C07—ORGANIC CHEMISTRY
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- 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
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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PCT/US1999/030730 WO2000038687A1 (fr) | 1998-12-23 | 1999-12-21 | Inhibiteurs de proteases |
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EP (1) | EP1158986A4 (fr) |
JP (1) | JP2002533397A (fr) |
KR (1) | KR100630986B1 (fr) |
CN (1) | CN1253441C (fr) |
AT (1) | ATE411294T1 (fr) |
AU (1) | AU768565B2 (fr) |
BR (1) | BR9916488A (fr) |
CA (1) | CA2356671A1 (fr) |
CZ (1) | CZ20012277A3 (fr) |
DE (1) | DE69939752D1 (fr) |
DZ (1) | DZ2977A1 (fr) |
ES (1) | ES2315456T3 (fr) |
GC (1) | GC0000178A (fr) |
HK (1) | HK1043536A1 (fr) |
HU (1) | HUP0104768A3 (fr) |
IL (2) | IL143142A0 (fr) |
NO (1) | NO318910B1 (fr) |
NZ (1) | NZ511710A (fr) |
PE (1) | PE20001340A1 (fr) |
PL (1) | PL350132A1 (fr) |
TR (1) | TR200101869T2 (fr) |
UY (1) | UY25874A1 (fr) |
WO (1) | WO2000038687A1 (fr) |
Families Citing this family (39)
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US20030144175A1 (en) | 1998-12-23 | 2003-07-31 | Smithkline Beecham Corporation | Protease inhibitors |
US6583137B1 (en) | 1999-11-10 | 2003-06-24 | Smithkline Beecham Corporation | Protease inhibitors |
JP2003513925A (ja) * | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテア−ゼ阻害剤 |
AU1474701A (en) * | 1999-11-10 | 2001-06-06 | Smithkline Beecham Corporation | Protease inhibitors |
JP2003513927A (ja) * | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテア−ゼ阻害剤 |
WO2001034565A2 (fr) * | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Inhibiteurs de protease |
US6596715B1 (en) | 1999-11-10 | 2003-07-22 | Smithkline Beecham Corporation | Protease inhibitors |
WO2001034153A1 (fr) * | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Inhibiteurs de proteases |
AU1474801A (en) | 1999-11-10 | 2001-06-06 | Smithkline Beecham Corporation | Protease inhibitors |
EP1231921A4 (fr) * | 1999-11-10 | 2004-06-23 | Smithkline Beecham Corp | Inhibiteurs de proteases |
JP2003513928A (ja) * | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
EP1233771A4 (fr) * | 1999-11-10 | 2003-05-14 | Smithkline Beecham Corp | Inhibiteurs de protease |
JP2003513922A (ja) * | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
US7071184B2 (en) | 2000-03-21 | 2006-07-04 | Smithkline Beecham Corporation | Protease inhibitors |
CO5280088A1 (es) * | 2000-04-18 | 2003-05-30 | Smithkline Beecham Corp | Inhibidores de proteasa |
CO5280093A1 (es) * | 2000-04-18 | 2003-05-30 | Smithkline Beecham Corp | Metodos de tratamiento |
AU2001268407A1 (en) * | 2000-06-14 | 2001-12-24 | Smithkline Beecham Corporation | Protease inhibitors |
AU2001286983A1 (en) * | 2000-09-01 | 2002-03-13 | Smith Kline Beecham Corporation | Method of treatment |
PL366232A1 (en) * | 2000-11-22 | 2005-01-24 | Smithkline Beecham Corporation | Protease inhibitors |
SI1370260T1 (sl) | 2001-02-20 | 2011-02-28 | Chugai Pharmaceutical Co Ltd | Azoli kot inhibitorji malonil-CoA dekarboksilaze, uporabni kot metabolični modulatorji |
US7709510B2 (en) | 2001-02-20 | 2010-05-04 | Chugai Seiyaku Kabushiki Kaisha | Azoles as malonyl-CoA decarboxylase inhibitors useful as metabolic modulators |
EP1401453A4 (fr) * | 2001-05-17 | 2005-04-06 | Smithkline Beecham Corp | Inhibiteurs de protease |
US6982263B2 (en) | 2001-06-08 | 2006-01-03 | Boehringer Ingelheim Pharmaceuticals, Inc. | Nitriles useful as reversible inhibitors of cysteine proteases |
AU2003263738A1 (en) * | 2002-05-22 | 2003-12-02 | Smithkline Beecham Corporation | Protease inhibitors |
US20050256105A1 (en) * | 2002-05-22 | 2005-11-17 | Jeong Jae U | Protease inhibitors |
KR100962972B1 (ko) | 2002-07-26 | 2010-06-09 | 주식회사유한양행 | 1-페닐피페리딘-3-온 유도체 및 그의 제조방법 |
AU2003273697A1 (en) * | 2002-10-08 | 2004-05-04 | Merck Frosst Canada Ltd | 4-amino-azepan-3-one compounds as cathepsin k inhibitors useful in the treatment of osteoporosis |
UA84420C2 (ru) | 2003-04-11 | 2008-10-27 | ПиТиСи ТЕРАПЬЮТИКС, ИНК. | СОЕДИНЕНИЯ 1,2,4-ОКСАДИАЗОЛБЕНЗОЙНОЙ КИСЛОТЫ, ФАРМАЦЕВТИЧЕСКАЯ КОМПОЗИЦИЯ (ВАРИАНТЫ) И ПРИМЕНЕНИЕ СОЕДИНЕНИЙ ДЛЯ ЛЕЧЕНИЯ ЗАБОЛЕВАНИЯ, СВЯЗАННОГО С ПРЕЖДЕВРЕМЕННОЙ ТЕРМИНАЦИЕЙ ТРАНСЛЯЦИИ ИЛИ НОНСЕНС-ОБУСЛОВЛЕННЫМ УМЕНЬШЕНИЕМ мРНК |
WO2005011670A1 (fr) * | 2003-08-01 | 2005-02-10 | Chugai Seiyaku Kabushiki Kaisha | Composes heterocycliques utiles comme inhibiteurs de la malonyl-coa decarboxylase |
ATE400272T1 (de) | 2003-08-01 | 2008-07-15 | Chugai Pharmaceutical Co Ltd | Piperidin-verbindungen als malonyl-coa decarboxylase-hemmer |
JP4773960B2 (ja) | 2003-08-01 | 2011-09-14 | 中外製薬株式会社 | マロニル−CoAデカルボキシラーゼ阻害剤として有用なシアノグアニジン型アゾール化合物 |
JP2007517810A (ja) * | 2004-01-08 | 2007-07-05 | メルク フロスト カナダ リミテツド | カテプシンシステインプロテアーゼ阻害剤 |
US20070293477A1 (en) * | 2004-09-07 | 2007-12-20 | Smithkline Beecham Corporation | Novel Compounds |
WO2007012180A1 (fr) * | 2005-07-26 | 2007-02-01 | Merck Frosst Canada Ltd. | Inhibiteurs de la cystéine protéase de la famille de la papaïne pour le traitement des maladies parasitaires |
JP5367563B2 (ja) | 2006-03-30 | 2013-12-11 | ピーティーシー セラピューティクス,インコーポレーテッド | ナンセンス突然変異を有するdnaからの機能的タンパク質の産生のための方法及びそれと関連した障害の治療 |
SG194842A1 (en) | 2011-05-16 | 2013-12-30 | Bayer Ip Gmbh | Use of cathepsin k inhibition for the treatment and/or prophylaxis of pulmonary hypertension and/or heart failure |
CN103275070A (zh) * | 2013-05-10 | 2013-09-04 | 郑彪 | 调节单核细胞增殖的四环化合物及其应用 |
CA3174516A1 (fr) | 2014-03-06 | 2015-09-11 | Ptc Therapeutics, Inc. | Compositions pharmaceutiques et sels d'un acide benzoique 1,2,4-oxadiazole |
WO2017075312A1 (fr) | 2015-10-30 | 2017-05-04 | Ptc Therapeutics, Inc. | Méthodes de traitement de l'épilepsie |
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IT1195287B (it) * | 1981-11-05 | 1988-10-12 | Ausonia Farma Srl | Derivato tiazolico,procedimento per la sua preparazione e relative composizioni farmaceutiche |
JPH05140063A (ja) * | 1991-11-19 | 1993-06-08 | Suntory Ltd | ジペプチド誘導体及びそれを有効成分とする骨疾患の予防及び治療剤 |
CA2111930A1 (fr) * | 1992-12-25 | 1994-06-26 | Ryoichi Ando | Derives d'aminocetones |
DK0603769T3 (da) * | 1992-12-25 | 1999-06-14 | Mitsubishi Chem Corp | Alfa-aminoketonderivater |
JPH06199850A (ja) * | 1992-12-28 | 1994-07-19 | Tanabe Seiyaku Co Ltd | インドール含有ペプチド及びその製法 |
US5883121A (en) * | 1995-12-12 | 1999-03-16 | Taiho Pharmaceutical Co., Ltd. | Epoxysuccinamide derivative or salt thereof, and medicine comprising the same |
US5902882A (en) * | 1996-04-17 | 1999-05-11 | Hoffmann-La Roche Inc. | Assymetric synthesis of azepines |
DZ2285A1 (fr) * | 1996-08-08 | 2002-12-25 | Smithkline Beecham Corp | Inhibiteurs de protéase de la cystéine. |
US6107291A (en) * | 1997-12-19 | 2000-08-22 | Amgen Inc. | Azepine or larger medium ring derivatives and methods of use |
JP2003513922A (ja) * | 1999-11-10 | 2003-04-15 | スミスクライン・ビーチャム・コーポレイション | プロテアーゼ阻害剤 |
WO2001034565A2 (fr) * | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Inhibiteurs de protease |
US6596715B1 (en) * | 1999-11-10 | 2003-07-22 | Smithkline Beecham Corporation | Protease inhibitors |
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AU1474701A (en) * | 1999-11-10 | 2001-06-06 | Smithkline Beecham Corporation | Protease inhibitors |
US6583137B1 (en) * | 1999-11-10 | 2003-06-24 | Smithkline Beecham Corporation | Protease inhibitors |
EP1233771A4 (fr) * | 1999-11-10 | 2003-05-14 | Smithkline Beecham Corp | Inhibiteurs de protease |
EP1231921A4 (fr) * | 1999-11-10 | 2004-06-23 | Smithkline Beecham Corp | Inhibiteurs de proteases |
AU1474801A (en) * | 1999-11-10 | 2001-06-06 | Smithkline Beecham Corporation | Protease inhibitors |
WO2001034153A1 (fr) * | 1999-11-10 | 2001-05-17 | Smithkline Beecham Corporation | Inhibiteurs de proteases |
NL1013996C2 (nl) * | 1999-12-30 | 2001-07-03 | Innas Free Piston Bv | Vrijezuiger aggregaat voor opwekken van hydraulische energie. |
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- 1999-12-21 BR BR9916488-4A patent/BR9916488A/pt not_active IP Right Cessation
- 1999-12-21 ES ES03076211T patent/ES2315456T3/es not_active Expired - Lifetime
- 1999-12-21 JP JP2000590640A patent/JP2002533397A/ja active Pending
- 1999-12-21 IL IL14314299A patent/IL143142A0/xx active IP Right Grant
- 1999-12-21 CA CA002356671A patent/CA2356671A1/fr not_active Abandoned
- 1999-12-21 AU AU19411/00A patent/AU768565B2/en not_active Ceased
- 1999-12-21 AT AT03076211T patent/ATE411294T1/de not_active IP Right Cessation
- 1999-12-21 HU HU0104768A patent/HUP0104768A3/hu unknown
- 1999-12-21 NZ NZ511710A patent/NZ511710A/en unknown
- 1999-12-22 GC GCP1999461 patent/GC0000178A/en active
- 1999-12-22 DZ DZ990277A patent/DZ2977A1/fr active
- 1999-12-22 UY UY25874A patent/UY25874A1/es not_active Application Discontinuation
- 1999-12-23 PE PE1999001312A patent/PE20001340A1/es not_active Application Discontinuation
-
2001
- 2001-05-14 IL IL143142A patent/IL143142A/en not_active IP Right Cessation
- 2001-06-22 NO NO20013124A patent/NO318910B1/no unknown
-
2002
- 2002-02-13 US US10/074,940 patent/US20020147188A1/en not_active Abandoned
- 2002-05-13 HK HK02103610.2A patent/HK1043536A1/zh unknown
-
2003
- 2003-04-01 US US10/404,142 patent/US20030225061A1/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
AU768565B2 (en) | 2003-12-18 |
NO20013124L (no) | 2001-06-22 |
HUP0104768A3 (en) | 2002-05-28 |
HUP0104768A2 (hu) | 2002-04-29 |
DE69939752D1 (de) | 2008-11-27 |
BR9916488A (pt) | 2001-10-09 |
JP2002533397A (ja) | 2002-10-08 |
DZ2977A1 (fr) | 2004-03-15 |
HK1043536A1 (zh) | 2002-09-20 |
WO2000038687A1 (fr) | 2000-07-06 |
NZ511710A (en) | 2003-12-19 |
EP1158986A1 (fr) | 2001-12-05 |
TR200101869T2 (tr) | 2002-01-21 |
KR100630986B1 (ko) | 2006-10-09 |
ATE411294T1 (de) | 2008-10-15 |
EP1158986A4 (fr) | 2002-03-27 |
PE20001340A1 (es) | 2001-01-28 |
CZ20012277A3 (cs) | 2001-11-14 |
US20030225061A1 (en) | 2003-12-04 |
ES2315456T3 (es) | 2009-04-01 |
IL143142A (en) | 2006-08-20 |
UY25874A1 (es) | 2001-08-27 |
KR20010089677A (ko) | 2001-10-08 |
CN1350458A (zh) | 2002-05-22 |
GC0000178A (en) | 2006-03-29 |
NO20013124D0 (no) | 2001-06-22 |
AU1941100A (en) | 2000-07-31 |
CN1253441C (zh) | 2006-04-26 |
IL143142A0 (en) | 2002-04-21 |
PL350132A1 (en) | 2002-11-04 |
CA2356671A1 (fr) | 2000-07-06 |
US20020147188A1 (en) | 2002-10-10 |
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