IL128668A - Rich in phosphinic acids as inhibitors of metalloproteases - Google Patents
Rich in phosphinic acids as inhibitors of metalloproteasesInfo
- Publication number
- IL128668A IL128668A IL12866897A IL12866897A IL128668A IL 128668 A IL128668 A IL 128668A IL 12866897 A IL12866897 A IL 12866897A IL 12866897 A IL12866897 A IL 12866897A IL 128668 A IL128668 A IL 128668A
- Authority
- IL
- Israel
- Prior art keywords
- alkyl
- compound
- hydroxy
- compounds
- aryl
- Prior art date
Links
- 239000011159 matrix material Substances 0.000 title description 25
- 239000003475 metalloproteinase inhibitor Substances 0.000 title description 4
- ACVYVLVWPXVTIT-UHFFFAOYSA-N phosphinic acid Chemical compound O[PH2]=O ACVYVLVWPXVTIT-UHFFFAOYSA-N 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 148
- -1 heterocycle-alkyl Chemical group 0.000 claims abstract description 60
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 35
- 125000002837 carbocyclic group Chemical group 0.000 claims abstract description 19
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 18
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims abstract description 15
- 239000001257 hydrogen Substances 0.000 claims abstract description 13
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 13
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 11
- 150000003839 salts Chemical class 0.000 claims abstract description 11
- 125000005127 aryl alkoxy alkyl group Chemical group 0.000 claims abstract description 10
- 150000002148 esters Chemical class 0.000 claims abstract description 10
- 230000003287 optical effect Effects 0.000 claims abstract description 10
- 125000004404 heteroalkyl group Chemical group 0.000 claims abstract description 9
- 125000003342 alkenyl group Chemical group 0.000 claims abstract description 7
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 7
- 150000003949 imides Chemical class 0.000 claims abstract description 7
- 125000006350 alkyl thio alkyl group Chemical group 0.000 claims abstract description 6
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 6
- 125000000304 alkynyl group Chemical group 0.000 claims abstract description 5
- 125000004103 aminoalkyl group Chemical group 0.000 claims abstract description 5
- 125000004474 heteroalkylene group Chemical group 0.000 claims abstract description 5
- 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims abstract description 3
- 125000005164 aryl thioalkyl group Chemical group 0.000 claims abstract description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract 5
- 125000004945 acylaminoalkyl group Chemical group 0.000 claims abstract 2
- 125000005041 acyloxyalkyl group Chemical group 0.000 claims abstract 2
- 125000004946 alkenylalkyl group Chemical group 0.000 claims abstract 2
- 125000005038 alkynylalkyl group Chemical group 0.000 claims abstract 2
- 102000005741 Metalloproteases Human genes 0.000 claims description 74
- 108010006035 Metalloproteases Proteins 0.000 claims description 74
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 56
- 230000000694 effects Effects 0.000 claims description 37
- 201000010099 disease Diseases 0.000 claims description 31
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- 125000000440 benzylamino group Chemical group [H]N(*)C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 13
- 238000002360 preparation method Methods 0.000 claims description 12
- 229940080818 propionamide Drugs 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 239000003814 drug Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 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 3
- 238000006467 substitution reaction Methods 0.000 claims description 3
- 125000001245 hexylamino group Chemical group [H]N([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- NTLKAXQBFYZMAH-UHFFFAOYSA-N 2-methylpentanamide Chemical compound CCCC(C)C(N)=O NTLKAXQBFYZMAH-UHFFFAOYSA-N 0.000 claims 1
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 11
- 125000000278 alkyl amino alkyl group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 105
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 105
- 239000000203 mixture Substances 0.000 description 77
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 62
- 238000000034 method Methods 0.000 description 44
- 238000006243 chemical reaction Methods 0.000 description 43
- 239000000243 solution Substances 0.000 description 39
- 238000011282 treatment Methods 0.000 description 31
- 239000003112 inhibitor Substances 0.000 description 29
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 28
- 239000007787 solid Substances 0.000 description 28
- 238000003756 stirring Methods 0.000 description 27
- 208000035475 disorder Diseases 0.000 description 25
- 210000001519 tissue Anatomy 0.000 description 25
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 24
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 19
- 239000003921 oil Substances 0.000 description 19
- 235000019198 oils Nutrition 0.000 description 19
- 239000000741 silica gel Substances 0.000 description 19
- 229910002027 silica gel Inorganic materials 0.000 description 19
- 239000003937 drug carrier Substances 0.000 description 18
- 239000000047 product Substances 0.000 description 18
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 16
- 125000004432 carbon atom Chemical group C* 0.000 description 14
- 125000000623 heterocyclic group Chemical group 0.000 description 14
- 238000004809 thin layer chromatography Methods 0.000 description 14
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
- 125000003118 aryl group Chemical group 0.000 description 13
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
- 230000015556 catabolic process Effects 0.000 description 12
- 229910052938 sodium sulfate Inorganic materials 0.000 description 12
- 235000011152 sodium sulphate Nutrition 0.000 description 12
- 102000004190 Enzymes Human genes 0.000 description 11
- 108090000790 Enzymes Proteins 0.000 description 11
- 241001465754 Metazoa Species 0.000 description 11
- 229940088598 enzyme Drugs 0.000 description 11
- 239000011541 reaction mixture Substances 0.000 description 11
- 239000011734 sodium Substances 0.000 description 11
- 239000003795 chemical substances by application Substances 0.000 description 10
- 239000002552 dosage form Substances 0.000 description 10
- 239000000126 substance Substances 0.000 description 10
- 239000003039 volatile agent Substances 0.000 description 10
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- 125000005842 heteroatom Chemical group 0.000 description 9
- 206010039073 rheumatoid arthritis Diseases 0.000 description 9
- 239000002253 acid Substances 0.000 description 8
- 125000004429 atom Chemical group 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 125000005843 halogen group Chemical group 0.000 description 8
- 230000002401 inhibitory effect Effects 0.000 description 8
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- 150000003254 radicals Chemical class 0.000 description 8
- 238000002560 therapeutic procedure Methods 0.000 description 8
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 description 7
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000003556 assay Methods 0.000 description 7
- 239000000969 carrier Substances 0.000 description 7
- 230000003197 catalytic effect Effects 0.000 description 7
- 239000003086 colorant Substances 0.000 description 7
- 239000000796 flavoring agent Substances 0.000 description 7
- 235000013355 food flavoring agent Nutrition 0.000 description 7
- 125000001072 heteroaryl group Chemical group 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 150000004702 methyl esters Chemical class 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 229920002472 Starch Polymers 0.000 description 6
- 235000001014 amino acid Nutrition 0.000 description 6
- 150000001413 amino acids Chemical class 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- OSGAYBCDTDRGGQ-UHFFFAOYSA-L calcium sulfate Chemical compound [Ca+2].[O-]S([O-])(=O)=O OSGAYBCDTDRGGQ-UHFFFAOYSA-L 0.000 description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 6
- 239000003085 diluting agent Substances 0.000 description 6
- 239000007788 liquid Substances 0.000 description 6
- 201000008482 osteoarthritis Diseases 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- 238000007634 remodeling Methods 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- 239000002904 solvent Substances 0.000 description 6
- 235000019698 starch Nutrition 0.000 description 6
- 125000001424 substituent group Chemical group 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 5
- 108010010803 Gelatin Proteins 0.000 description 5
- 206010027476 Metastases Diseases 0.000 description 5
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 5
- 102000035195 Peptidases Human genes 0.000 description 5
- 108091005804 Peptidases Proteins 0.000 description 5
- 239000004365 Protease Substances 0.000 description 5
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 5
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 5
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 5
- 229930006000 Sucrose Natural products 0.000 description 5
- GXJPMBQLUDQIAV-NKWVEPMBSA-N [(4r,5s)-5-ethenyl-2,2-dimethyl-1,3-dioxolan-4-yl]methanol Chemical compound CC1(C)O[C@H](CO)[C@H](C=C)O1 GXJPMBQLUDQIAV-NKWVEPMBSA-N 0.000 description 5
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 5
- 230000033228 biological regulation Effects 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
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- 208000015181 infectious disease Diseases 0.000 description 5
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- 230000009401 metastasis Effects 0.000 description 5
- HIVDOHPKFIBYPZ-SECBINFHSA-N methyl (2r)-2-(benzylamino)propanoate Chemical compound COC(=O)[C@@H](C)NCC1=CC=CC=C1 HIVDOHPKFIBYPZ-SECBINFHSA-N 0.000 description 5
- QVDXUKJJGUSGLS-ZCFIWIBFSA-N methyl (2r)-2-amino-4-methylpentanoate Chemical compound COC(=O)[C@H](N)CC(C)C QVDXUKJJGUSGLS-ZCFIWIBFSA-N 0.000 description 5
- DODCBMODXGJOKD-FYZOBXCZSA-N methyl (2r)-2-amino-4-methylpentanoate;hydrochloride Chemical compound Cl.COC(=O)[C@H](N)CC(C)C DODCBMODXGJOKD-FYZOBXCZSA-N 0.000 description 5
- 235000018102 proteins Nutrition 0.000 description 5
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- 230000037390 scarring Effects 0.000 description 5
- 239000001632 sodium acetate Substances 0.000 description 5
- 235000017281 sodium acetate Nutrition 0.000 description 5
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 5
- 239000007858 starting material Substances 0.000 description 5
- 239000005720 sucrose Substances 0.000 description 5
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- 230000008685 targeting Effects 0.000 description 5
- GUBGYTABKSRVRQ-XLOQQCSPSA-N Alpha-Lactose Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@H]1O[C@@H]1[C@@H](CO)O[C@H](O)[C@H](O)[C@H]1O GUBGYTABKSRVRQ-XLOQQCSPSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
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- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 4
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- LITWZVHRFAQHQA-CYBMUJFWSA-N methyl (2r)-2-(benzylamino)-4-methylpentanoate Chemical compound COC(=O)[C@@H](CC(C)C)NCC1=CC=CC=C1 LITWZVHRFAQHQA-CYBMUJFWSA-N 0.000 description 4
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- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
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- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 3
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- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
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- C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
- C07F9/36—Amides thereof
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- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/576—Six-membered rings
- C07F9/58—Pyridine rings
-
- 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
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/6553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms
- C07F9/655345—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having sulfur atoms, with or without selenium or tellurium atoms, as the only ring hetero atoms the sulfur atom being part of a five-membered ring
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Molecular Biology (AREA)
- Biochemistry (AREA)
- Physical Education & Sports Medicine (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Immunology (AREA)
- Ophthalmology & Optometry (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Biomedical Technology (AREA)
- Heart & Thoracic Surgery (AREA)
- Cardiology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US2476596P | 1996-08-28 | 1996-08-28 | |
PCT/US1997/014556 WO1998008853A1 (en) | 1996-08-28 | 1997-08-22 | Phosphinic acid amides as matrix metalloprotease inhibitors |
Publications (2)
Publication Number | Publication Date |
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IL128668A0 IL128668A0 (en) | 2000-01-31 |
IL128668A true IL128668A (en) | 2002-02-10 |
Family
ID=21822291
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IL12866897A IL128668A (en) | 1996-08-28 | 1997-08-22 | Rich in phosphinic acids as inhibitors of metalloproteases |
Country Status (27)
Country | Link |
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US (1) | US5830915A (no) |
EP (1) | EP0925303B1 (no) |
JP (1) | JP3539736B2 (no) |
KR (1) | KR20000035925A (no) |
CN (1) | CN1228780A (no) |
AR (1) | AR009357A1 (no) |
AT (1) | ATE226590T1 (no) |
AU (1) | AU732653B2 (no) |
BR (1) | BR9713182A (no) |
CA (1) | CA2264254C (no) |
CO (1) | CO4900033A1 (no) |
CZ (1) | CZ63699A3 (no) |
DE (1) | DE69716619T2 (no) |
DK (1) | DK0925303T3 (no) |
HU (1) | HUP9903916A3 (no) |
ID (1) | ID18145A (no) |
IL (1) | IL128668A (no) |
NO (1) | NO990857L (no) |
NZ (1) | NZ334258A (no) |
PE (1) | PE107698A1 (no) |
PL (1) | PL331854A1 (no) |
RU (1) | RU2170232C2 (no) |
SK (1) | SK25499A3 (no) |
TR (1) | TR199900399T2 (no) |
TW (1) | TW518338B (no) |
WO (1) | WO1998008853A1 (no) |
ZA (1) | ZA977700B (no) |
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US20030206874A1 (en) * | 1996-11-21 | 2003-11-06 | The Proctor & Gamble Company | Promoting whole body health |
WO1999006340A2 (en) * | 1997-07-31 | 1999-02-11 | The Procter & Gamble Company | Sulfonylamino substituted hydroxamic acid derivatives as metalloprotease inhibitors |
US6846478B1 (en) | 1998-02-27 | 2005-01-25 | The Procter & Gamble Company | Promoting whole body health |
DE19850072A1 (de) | 1998-10-30 | 2000-05-04 | Bayer Ag | Phosphinat-Peptidanaloga zur Behandlung von fibrotischen Erkrankungen |
US6753337B2 (en) | 1999-01-27 | 2004-06-22 | Wyeth Holdings Corporation | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase/tace inhibitors |
US6762178B2 (en) | 1999-01-27 | 2004-07-13 | Wyeth Holdings Corporation | Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors |
US6277885B1 (en) | 1999-01-27 | 2001-08-21 | American Cyanamid Company | Acetylenic aryl sulfonamide and phosphinic acid amide hydroxamic acid TACE inhibitors |
WO2000044723A1 (en) | 1999-01-27 | 2000-08-03 | American Cyanamid Company | Alkynyl containing hydroxamic acid derivatives, their preparation and their use as matrix metalloproteinase (mmp) inhibitors/tnf-alpha converting enzyme (tace) inhibitors |
US6340691B1 (en) | 1999-01-27 | 2002-01-22 | American Cyanamid Company | Alkynyl containing hydroxamic acid compounds as matrix metalloproteinase and tace inhibitors |
US6326516B1 (en) | 1999-01-27 | 2001-12-04 | American Cyanamid Company | Acetylenic β-sulfonamido and phosphinic acid amide hydroxamic acid TACE inhibitors |
EA200100810A1 (ru) * | 1999-01-27 | 2002-02-28 | Американ Цианамид Компани | Гидроксамовые кислоты на основе ацетиленового арилсульфонамида и амида фосфиновой кислоты, действующие как ингибиторы tace |
US6225311B1 (en) | 1999-01-27 | 2001-05-01 | American Cyanamid Company | Acetylenic α-amino acid-based sulfonamide hydroxamic acid tace inhibitors |
US6200996B1 (en) | 1999-01-27 | 2001-03-13 | American Cyanamid Company | Heteroaryl acetylenic sulfonamide and phosphinic acid amide hydroxamic acid tace inhibitors |
US6946473B2 (en) | 1999-01-27 | 2005-09-20 | Wyeth Holdings Corporation | Preparation and use of acetylenic ortho-sulfonamido and phosphinic acid amido bicyclic heteroaryl hydroxamic acids as TACE inhibitors |
US6313123B1 (en) | 1999-01-27 | 2001-11-06 | American Cyanamid Company | Acetylenic sulfonamide thiol tace inhibitors |
AR035313A1 (es) * | 1999-01-27 | 2004-05-12 | Wyeth Corp | Inhibidores de tace acetilenicos de acido hidroxamico de sulfonamida a base de alfa-aminoacidos, composiciones farmaceuticas y el uso de los mismos para la manufactura de medicamentos. |
BR0008716A (pt) | 1999-03-03 | 2002-09-24 | Procter & Gamble | Inibidores de metaloprotease contendo alquenil ou alquinil |
US6297337B1 (en) | 1999-05-19 | 2001-10-02 | Pmd Holdings Corp. | Bioadhesive polymer compositions |
US6312474B1 (en) * | 1999-09-15 | 2001-11-06 | Bio-Vascular, Inc. | Resorbable implant materials |
PE20020102A1 (es) * | 2000-06-30 | 2002-03-06 | Procter & Gamble | Composicion topica oral que comprende un agente modulador de la respuesta del huesped frente a patogenos periodontales |
CN1287803C (zh) * | 2000-06-30 | 2006-12-06 | 宝洁公司 | 促进全身健康的局部口腔组合物及其应用 |
US8283135B2 (en) * | 2000-06-30 | 2012-10-09 | The Procter & Gamble Company | Oral care compositions containing combinations of anti-bacterial and host-response modulating agents |
EP1303527B1 (en) * | 2000-07-18 | 2004-09-29 | Leo Pharma A/S | Matrix metalloproteinase inhibitors |
FR2814950B1 (fr) * | 2000-10-05 | 2003-08-08 | Oreal | Utilisation d'au moins un extrait d'au moins un vegetal de la famille des ericaceae, dans des compositions destinees a traiter les signes cutanes du vieillissement |
US6376514B1 (en) | 2000-10-17 | 2002-04-23 | The Procter & Gamble Co. | Substituted six-membered heterocyclic compounds useful for treating multidrug resistance and compositions and methods thereof |
US6693099B2 (en) * | 2000-10-17 | 2004-02-17 | The Procter & Gamble Company | Substituted piperazine compounds optionally containing a quinolyl moiety for treating multidrug resistance |
EP1440057A1 (en) | 2001-11-01 | 2004-07-28 | Wyeth Holdings Corporation | Allenic aryl sulfonamide hydroxamic acids as matrix metalloproteinase and tace inhibitors |
PE20030701A1 (es) * | 2001-12-20 | 2003-08-21 | Schering Corp | Compuestos para el tratamiento de trastornos inflamatorios |
AU2003205544A1 (en) | 2002-01-18 | 2003-07-30 | Leo Pharma A/S | Mmp inhibitors |
AU2003304456A1 (en) | 2002-12-23 | 2005-03-16 | Wyeth Holdings Corporation | Acetylenic aryl sulfonate hydroxamic acid tace and matrix metalloproteinase inhibitors |
EP1594459B1 (en) | 2002-12-30 | 2010-02-17 | Angiotech International Ag | Drug delivery from rapid gelling polymer composition |
US7144588B2 (en) | 2003-01-17 | 2006-12-05 | Synovis Life Technologies, Inc. | Method of preventing surgical adhesions |
EP1449538A1 (en) | 2003-02-21 | 2004-08-25 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibition of TACE or amphiregulin for the modulation of EGF receptor signal transactivation |
WO2008111371A1 (ja) * | 2007-03-09 | 2008-09-18 | National University Corporation Nagoya University | ホスホロアミド化合物及びその製造方法、配位子、錯体、触媒、及び光学活性アルコールの製造方法 |
TW201141536A (en) | 2009-12-21 | 2011-12-01 | Colgate Palmolive Co | Oral care compositions and methods |
EP2726073A1 (en) * | 2011-06-29 | 2014-05-07 | Janssen Pharmaceutica, N.V. | Methods of treatment using allosteric processing inhibitors for matrix metalloproteinases |
RU2488587C1 (ru) * | 2012-05-23 | 2013-07-27 | Федеральное государственное бюджетное образовательное учреждение высшего профессионального образования "Казанский национальный исследовательский технологический университет" | Анилид гидроксиметиланилинометилфосфиновой кислоты (амидофос) в качестве биостимулятора активного ила в процессе очистки сточных вод и способ его получения |
EP3364958B1 (en) | 2015-10-23 | 2023-01-04 | Navitor Pharmaceuticals, Inc. | Modulators of sestrin-gator2 interaction and uses thereof |
US20190008828A1 (en) | 2015-12-28 | 2019-01-10 | The U.S.A., As Represented By The Secretary Department Of Health And Human Services | Methods for inhibiting human immunodeficiency virus (hiv) release from infected cells |
WO2017133517A1 (zh) * | 2016-02-03 | 2017-08-10 | 四川海思科制药有限公司 | 一种磷酰胺衍生物及制备方法和用途 |
KR20230049762A (ko) * | 2016-04-29 | 2023-04-13 | 오피렉스, 인크. | 벌목 유독동물독소중독으로 인한 용혈, 뇌부종, 및 급성 신손상의 치료를 위한 pla2 및 hmg-coa 억제제 |
CN106905183B (zh) * | 2017-02-24 | 2018-07-31 | 三峡大学 | 一类含氨基的ɑ-酰氧基羰基酰胺类衍生物,制备方法及其应用 |
EP3615019A4 (en) * | 2017-04-26 | 2021-01-27 | Navitor Pharmaceuticals, Inc. | MODULATORS OF SESTRIN-GATOR2 INTERACTION AND USES THEREOF |
EP3870158A4 (en) | 2018-10-24 | 2022-08-10 | Navitor Pharmaceuticals, Inc. | POLYMORPHIC COMPOUNDS AND USES THEREOF |
CN114786660A (zh) | 2019-11-01 | 2022-07-22 | 纳维托制药有限公司 | 使用mtorc1调节剂的治疗方法 |
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GB8601368D0 (en) * | 1986-01-21 | 1986-02-26 | Ici America Inc | Hydroxamic acids |
DK77487A (da) * | 1986-03-11 | 1987-09-12 | Hoffmann La Roche | Hydroxylaminderivater |
FR2609289B1 (fr) * | 1987-01-06 | 1991-03-29 | Bellon Labor Sa Roger | Nouveaux composes a activite d'inhibiteurs de collagenase, procede pour les preparer et compositions pharmaceutiques contenant ces composes |
GB8827305D0 (en) * | 1988-11-23 | 1988-12-29 | British Bio Technology | Compounds |
GB8919251D0 (en) * | 1989-08-24 | 1989-10-04 | British Bio Technology | Compounds |
DE4011172A1 (de) * | 1990-04-06 | 1991-10-10 | Degussa | Verbindungen zur bekaempfung von pflanzenkrankheiten |
US5183900A (en) * | 1990-11-21 | 1993-02-02 | Galardy Richard E | Matrix metalloprotease inhibitors |
US5189178A (en) * | 1990-11-21 | 1993-02-23 | Galardy Richard E | Matrix metalloprotease inhibitors |
GB9102635D0 (en) * | 1991-02-07 | 1991-03-27 | British Bio Technology | Compounds |
GB9107368D0 (en) * | 1991-04-08 | 1991-05-22 | Smithkline Beecham Plc | Novel compounds |
IL98681A (en) * | 1991-06-30 | 1997-06-10 | Yeda Rehovot And Dev Company L | Pharmaceutical compositions comprising hydroxamate derivatives for iron removal from mammalian cells and from pathogenic organisms and some novel hydroxamate derivatives |
DE4127842A1 (de) * | 1991-08-22 | 1993-02-25 | Rhone Poulenc Rorer Gmbh | 5-((omega)-arylalky)-2-thienyl alkansaeuren, ihre salze und/oder ihre derivate |
JPH05125029A (ja) * | 1991-11-06 | 1993-05-21 | Yamanouchi Pharmaceut Co Ltd | 新規なアミド化合物又はその塩 |
DE69309047T2 (de) * | 1992-04-07 | 1997-09-11 | British Biotech Pharm | Hydroxamsäure enthaltende collagenase-inhibitoren und cytokinaktivitätsinhibitoren |
AU4267293A (en) * | 1992-05-01 | 1993-11-29 | British Biotech Pharmaceuticals Limited | Use of MMP inhibitors |
AU666727B2 (en) * | 1992-06-25 | 1996-02-22 | F. Hoffmann-La Roche Ag | Hydroxamic acid derivatives |
GB9215665D0 (en) * | 1992-07-23 | 1992-09-09 | British Bio Technology | Compounds |
GB9223904D0 (en) * | 1992-11-13 | 1993-01-06 | British Bio Technology | Inhibition of cytokine production |
US5455258A (en) * | 1993-01-06 | 1995-10-03 | Ciba-Geigy Corporation | Arylsulfonamido-substituted hydroxamic acids |
US5514716A (en) * | 1994-02-25 | 1996-05-07 | Sterling Winthrop, Inc. | Hydroxamic acid and carboxylic acid derivatives, process for their preparation and use thereof |
JPH10507158A (ja) * | 1994-06-22 | 1998-07-14 | ブリティッシュ バイオテック ファーマシューティカルズ リミテッド | 金属タンパク質分解酵素阻害剤 |
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1997
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- 1997-08-22 AU AU41531/97A patent/AU732653B2/en not_active Ceased
- 1997-08-22 JP JP51171698A patent/JP3539736B2/ja not_active Expired - Fee Related
- 1997-08-22 CZ CZ99636A patent/CZ63699A3/cs unknown
- 1997-08-22 AT AT97939444T patent/ATE226590T1/de not_active IP Right Cessation
- 1997-08-22 EP EP97939444A patent/EP0925303B1/en not_active Expired - Lifetime
- 1997-08-22 DK DK97939444T patent/DK0925303T3/da active
- 1997-08-22 CA CA002264254A patent/CA2264254C/en not_active Expired - Fee Related
- 1997-08-22 BR BR9713182-2A patent/BR9713182A/pt unknown
- 1997-08-22 RU RU99106245/04A patent/RU2170232C2/ru active
- 1997-08-22 PL PL97331854A patent/PL331854A1/xx unknown
- 1997-08-22 HU HU9903916A patent/HUP9903916A3/hu unknown
- 1997-08-22 IL IL12866897A patent/IL128668A/en not_active IP Right Cessation
- 1997-08-22 DE DE69716619T patent/DE69716619T2/de not_active Expired - Fee Related
- 1997-08-22 NZ NZ334258A patent/NZ334258A/xx unknown
- 1997-08-22 TR TR1999/00399T patent/TR199900399T2/xx unknown
- 1997-08-22 WO PCT/US1997/014556 patent/WO1998008853A1/en not_active Application Discontinuation
- 1997-08-22 SK SK254-99A patent/SK25499A3/sk unknown
- 1997-08-22 CN CN97197546A patent/CN1228780A/zh active Pending
- 1997-08-26 US US08/918,950 patent/US5830915A/en not_active Expired - Fee Related
- 1997-08-27 AR ARP970103898A patent/AR009357A1/es unknown
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- 1997-08-27 ZA ZA9707700A patent/ZA977700B/xx unknown
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- 1997-08-28 ID IDP972999A patent/ID18145A/id unknown
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1998
- 1998-02-03 TW TW087101222A patent/TW518338B/zh active
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1999
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Also Published As
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PL331854A1 (en) | 1999-08-16 |
JP3539736B2 (ja) | 2004-07-07 |
SK25499A3 (en) | 2000-03-13 |
CO4900033A1 (es) | 2000-03-27 |
NO990857D0 (no) | 1999-02-23 |
CN1228780A (zh) | 1999-09-15 |
NO990857L (no) | 1999-04-28 |
CZ63699A3 (cs) | 1999-07-14 |
EP0925303B1 (en) | 2002-10-23 |
IL128668A0 (en) | 2000-01-31 |
BR9713182A (pt) | 1999-11-03 |
HUP9903916A3 (en) | 2001-06-28 |
DE69716619T2 (de) | 2003-06-26 |
ZA977700B (en) | 1998-02-23 |
KR20000035925A (ko) | 2000-06-26 |
ID18145A (id) | 1998-03-05 |
WO1998008853A1 (en) | 1998-03-05 |
AU732653B2 (en) | 2001-04-26 |
HUP9903916A2 (hu) | 2001-05-28 |
EP0925303A1 (en) | 1999-06-30 |
NZ334258A (en) | 2000-11-24 |
JP2000515167A (ja) | 2000-11-14 |
CA2264254C (en) | 2003-03-11 |
DK0925303T3 (da) | 2003-02-24 |
PE107698A1 (es) | 1999-02-11 |
AR009357A1 (es) | 2000-04-12 |
DE69716619D1 (en) | 2002-11-28 |
AU4153197A (en) | 1998-03-19 |
RU2170232C2 (ru) | 2001-07-10 |
CA2264254A1 (en) | 1998-03-05 |
TW518338B (en) | 2003-01-21 |
ATE226590T1 (de) | 2002-11-15 |
TR199900399T2 (xx) | 1999-06-21 |
US5830915A (en) | 1998-11-03 |
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