NO315371B1 - Substituerte sykliske amin-metallprotease-inhibitorer - Google Patents

Substituerte sykliske amin-metallprotease-inhibitorer Download PDF

Info

Publication number: NO315371B1
Authority: NO; Norway
Prior art keywords: hydroxycarboxamide; methoxyphenylsulfonyl; mmol; pyrrolidine; silica gel
Prior art date: 1996-08-28

Application number

NO19990855A

Other languages

English (en)

Norwegian (no)

Other versions

NO990855L (no

NO990855D0 (no

Inventor

Michael George Natchus

Biswanath De

Stanislaw Pikul

Neil Gregory Almstead

Roger Gunnard Bookland

Yetunde Olabisi Taiwo

Menyan Cheng

Original Assignee

Procter & Gamble

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1996-08-28

Filing date

1999-02-23

Publication date

2003-08-25

1999-02-23 Application filed by Procter & Gamble filed Critical Procter & Gamble

1999-02-23 Publication of NO990855D0 publication Critical patent/NO990855D0/no

1999-04-23 Publication of NO990855L publication Critical patent/NO990855L/no

2003-08-25 Publication of NO315371B1 publication Critical patent/NO315371B1/no

Links

-1 cyclic amine Chemical class 0.000 title claims description 53
229910052751 metal Inorganic materials 0.000 title description 4
239000002184 metal Substances 0.000 title description 4
229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title 1
239000000137 peptide hydrolase inhibitor Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 249
102000005741 Metalloproteases Human genes 0.000 claims abstract description 76
108010006035 Metalloproteases Proteins 0.000 claims abstract description 76
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 62
230000000694 effects Effects 0.000 claims abstract description 39
201000010099 disease Diseases 0.000 claims abstract description 33
239000008194 pharmaceutical composition Substances 0.000 claims abstract description 11
RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 165
238000011282 treatment Methods 0.000 claims description 48
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 25
229910052739 hydrogen Inorganic materials 0.000 claims description 16
239000001257 hydrogen Substances 0.000 claims description 14
150000003839 salts Chemical class 0.000 claims description 14
238000002360 preparation method Methods 0.000 claims description 12
125000000217 alkyl group Chemical group 0.000 claims description 11
150000002431 hydrogen Chemical class 0.000 claims description 11
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
125000001072 heteroaryl group Chemical group 0.000 claims description 9
230000003287 optical effect Effects 0.000 claims description 9
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 5
229910052736 halogen Inorganic materials 0.000 claims description 5
150000002367 halogens Chemical class 0.000 claims description 5
125000004404 heteroalkyl group Chemical group 0.000 claims description 5
125000002757 morpholinyl group Chemical group 0.000 claims description 5
125000004076 pyridyl group Chemical group 0.000 claims description 5
ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical group C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
125000002883 imidazolyl group Chemical group 0.000 claims description 4
125000002541 furyl group Chemical group 0.000 claims description 3
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 3
125000003386 piperidinyl group Chemical group 0.000 claims description 3
125000003373 pyrazinyl group Chemical group 0.000 claims description 3
125000000714 pyrimidinyl group Chemical group 0.000 claims description 3
125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 3
238000006467 substitution reaction Methods 0.000 claims description 3
125000001544 thienyl group Chemical group 0.000 claims description 3
CZSRXHJVZUBEGW-UHFFFAOYSA-N 1,2-thiazolidine Chemical group C1CNSC1 CZSRXHJVZUBEGW-UHFFFAOYSA-N 0.000 claims description 2
206010006895 Cachexia Diseases 0.000 claims description 2
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 2
239000004305 biphenyl Substances 0.000 claims description 2
235000010290 biphenyl Nutrition 0.000 claims description 2
125000001188 haloalkyl group Chemical group 0.000 claims description 2
125000005059 halophenyl group Chemical group 0.000 claims description 2
125000005553 heteroaryloxy group Chemical group 0.000 claims description 2
125000005554 pyridyloxy group Chemical group 0.000 claims description 2
125000004568 thiomorpholinyl group Chemical group 0.000 claims description 2
125000004356 hydroxy functional group Chemical group O* 0.000 claims 3
208000023178 Musculoskeletal disease Diseases 0.000 claims 1
125000001475 halogen functional group Chemical group 0.000 claims 1
208000017445 musculoskeletal system disease Diseases 0.000 claims 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
238000000034 method Methods 0.000 abstract description 41
239000003112 inhibitor Substances 0.000 abstract description 31
102000004190 Enzymes Human genes 0.000 abstract description 12
108090000790 Enzymes Proteins 0.000 abstract description 12
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 528
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 483
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 303
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 227
235000019439 ethyl acetate Nutrition 0.000 description 223
239000000741 silica gel Substances 0.000 description 220
229910002027 silica gel Inorganic materials 0.000 description 220
239000000203 mixture Substances 0.000 description 191
238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 117
239000007787 solid Substances 0.000 description 95
239000000243 solution Substances 0.000 description 78
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 70
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 57
239000002904 solvent Substances 0.000 description 55
150000004702 methyl esters Chemical class 0.000 description 52
239000011734 sodium Substances 0.000 description 44
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 43
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 41
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 41
239000012044 organic layer Substances 0.000 description 41
239000000047 product Substances 0.000 description 41
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 38
RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 38
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 37
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 35
239000012267 brine Substances 0.000 description 29
208000035475 disorder Diseases 0.000 description 29
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 29
150000002148 esters Chemical class 0.000 description 28
239000003921 oil Substances 0.000 description 28
235000019198 oils Nutrition 0.000 description 28
RVWMQSODNUSUBL-UHFFFAOYSA-N potassium;oxidoamine Chemical compound [K+].[O-]N RVWMQSODNUSUBL-UHFFFAOYSA-N 0.000 description 28
239000000460 chlorine Substances 0.000 description 27
239000000463 material Substances 0.000 description 26
239000011541 reaction mixture Substances 0.000 description 26
210000001519 tissue Anatomy 0.000 description 22
FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 20
FAMRKDQNMBBFBR-UHFFFAOYSA-N ethyl n-ethoxycarbonyliminocarbamate Chemical compound CCOC(=O)N=NC(=O)OCC FAMRKDQNMBBFBR-UHFFFAOYSA-N 0.000 description 20
239000000843 powder Substances 0.000 description 20
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 18
239000003937 drug carrier Substances 0.000 description 18
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 17
239000011521 glass Substances 0.000 description 17
150000001412 amines Chemical class 0.000 description 16
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 14
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 14
239000002253 acid Substances 0.000 description 14
238000010438 heat treatment Methods 0.000 description 13
239000010410 layer Substances 0.000 description 13
DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 12
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 11
238000006243 chemical reaction Methods 0.000 description 11
239000003795 chemical substances by application Substances 0.000 description 11
229940088598 enzyme Drugs 0.000 description 11
150000003141 primary amines Chemical class 0.000 description 11
238000000746 purification Methods 0.000 description 11
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 10
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 10
241001465754 Metazoa Species 0.000 description 10
230000015556 catabolic process Effects 0.000 description 10
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
241000124008 Mammalia Species 0.000 description 9
239000013078 crystal Substances 0.000 description 9
239000002552 dosage form Substances 0.000 description 9
239000000706 filtrate Substances 0.000 description 9
SBMSLRMNBSMKQC-UHFFFAOYSA-N pyrrolidin-1-amine Chemical compound NN1CCCC1 SBMSLRMNBSMKQC-UHFFFAOYSA-N 0.000 description 9
238000003756 stirring Methods 0.000 description 9
FGMPLJWBKKVCDB-SCSAIBSYSA-N (2r)-1-hydroxypyrrolidine-2-carboxylic acid Chemical compound ON1CCC[C@@H]1C(O)=O FGMPLJWBKKVCDB-SCSAIBSYSA-N 0.000 description 8
YXIWHUQXZSMYRE-UHFFFAOYSA-N 1,3-benzothiazole-2-thiol Chemical compound C1=CC=C2SC(S)=NC2=C1 YXIWHUQXZSMYRE-UHFFFAOYSA-N 0.000 description 8
LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 description 8
VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 8
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium on carbon Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 8
235000011114 ammonium hydroxide Nutrition 0.000 description 8
229910052786 argon Inorganic materials 0.000 description 8
125000004432 carbon atom Chemical group C* 0.000 description 8
239000013058 crude material Substances 0.000 description 8
239000006196 drop Substances 0.000 description 8
230000002265 prevention Effects 0.000 description 8
206010039073 rheumatoid arthritis Diseases 0.000 description 8
210000003491 skin Anatomy 0.000 description 8
239000000126 substance Substances 0.000 description 8
125000001424 substituent group Chemical group 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
OISVCGZHLKNMSJ-UHFFFAOYSA-N 2,6-dimethylpyridine Chemical compound CC1=CC=CC(C)=N1 OISVCGZHLKNMSJ-UHFFFAOYSA-N 0.000 description 7
DTJVECUKADWGMO-UHFFFAOYSA-N 4-methoxybenzenesulfonyl chloride Chemical compound COC1=CC=C(S(Cl)(=O)=O)C=C1 DTJVECUKADWGMO-UHFFFAOYSA-N 0.000 description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
206010028980 Neoplasm Diseases 0.000 description 7
102000035195 Peptidases Human genes 0.000 description 7
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239000004365 Protease Substances 0.000 description 7
238000003556 assay Methods 0.000 description 7
239000000969 carrier Substances 0.000 description 7
239000003153 chemical reaction reagent Substances 0.000 description 7
239000012043 crude product Substances 0.000 description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 description 7
239000003446 ligand Substances 0.000 description 7
229910052943 magnesium sulfate Inorganic materials 0.000 description 7
235000019341 magnesium sulphate Nutrition 0.000 description 7
239000011780 sodium chloride Substances 0.000 description 7
239000008247 solid mixture Substances 0.000 description 7
239000000725 suspension Substances 0.000 description 7
238000002560 therapeutic procedure Methods 0.000 description 7
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 6
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
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230000003197 catalytic effect Effects 0.000 description 6
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HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
238000007911 parenteral administration Methods 0.000 description 6
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OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 4
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 4
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229910052757 nitrogen Inorganic materials 0.000 description 4
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238000003786 synthesis reaction Methods 0.000 description 4
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Classifications

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- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/42—Nitro radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
- C07D207/48—Sulfur atoms
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Landscapes

Health & Medical Sciences (AREA)
Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
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Ophthalmology & Optometry (AREA)
Immunology (AREA)
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Diabetes (AREA)
Hematology (AREA)
Obesity (AREA)
Cardiology (AREA)
Biomedical Technology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Plural Heterocyclic Compounds (AREA)
Pyrrole Compounds (AREA)
Confectionery (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Catalysts (AREA)
Peptides Or Proteins (AREA)
Hydrogenated Pyridines (AREA)

NO19990855A 1996-08-28 1999-02-23 Substituerte sykliske amin-metallprotease-inhibitorer NO315371B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
US2484296P	1996-08-28	1996-08-28
PCT/US1997/014555 WO1998008815A1 (en)	1996-08-28	1997-08-22	Substituted cyclic amine metalloprotease inhibitors

Publications (3)

Publication Number	Publication Date
NO990855D0 NO990855D0 (no)	1999-02-23
NO990855L NO990855L (no)	1999-04-23
NO315371B1 true NO315371B1 (no)	2003-08-25

Family

ID=21822685

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO19990855A NO315371B1 (no)	1996-08-28	1999-02-23	Substituerte sykliske amin-metallprotease-inhibitorer

Country Status (30)

Country	Link
US (6)	US6417219B1 (id)
EP (1)	EP0927161B1 (id)
JP (2)	JP3541043B2 (id)
KR (1)	KR100323272B1 (id)
CN (1)	CN1232451A (id)
AT (1)	ATE226193T1 (id)
AU (1)	AU741893B2 (id)
BR (1)	BR9713465A (id)
CA (1)	CA2263928A1 (id)
CO (1)	CO4900036A1 (id)
CZ (1)	CZ63199A3 (id)
DE (1)	DE69716449T2 (id)
DK (1)	DK0927161T3 (id)
ES (1)	ES2201318T3 (id)
HK (1)	HK1020962A1 (id)
HU (1)	HUP0000478A3 (id)
ID (1)	ID18143A (id)
IL (1)	IL128666A (id)
MY (1)	MY116959A (id)
NO (1)	NO315371B1 (id)
NZ (1)	NZ334256A (id)
PE (1)	PE109098A1 (id)
PL (1)	PL331802A1 (id)
PT (1)	PT927161E (id)
RU (1)	RU2221782C2 (id)
SK (1)	SK25099A3 (id)
TR (1)	TR199900431T2 (id)
TW (1)	TWI232218B (id)
WO (1)	WO1998008815A1 (id)
ZA (1)	ZA977698B (id)

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1997
- 1997-08-22 AU AU40741/97A patent/AU741893B2/en not_active Ceased
- 1997-08-22 PT PT97938412T patent/PT927161E/pt unknown
- 1997-08-22 HU HU0000478A patent/HUP0000478A3/hu unknown
- 1997-08-22 WO PCT/US1997/014555 patent/WO1998008815A1/en active IP Right Grant
- 1997-08-22 DK DK97938412T patent/DK0927161T3/da active
- 1997-08-22 EP EP97938412A patent/EP0927161B1/en not_active Expired - Lifetime
- 1997-08-22 ES ES97938412T patent/ES2201318T3/es not_active Expired - Lifetime
- 1997-08-22 AT AT97938412T patent/ATE226193T1/de not_active IP Right Cessation
- 1997-08-22 CA CA002263928A patent/CA2263928A1/en not_active Abandoned
- 1997-08-22 JP JP51171598A patent/JP3541043B2/ja not_active Expired - Fee Related
- 1997-08-22 RU RU99106522/04A patent/RU2221782C2/ru not_active IP Right Cessation
- 1997-08-22 IL IL12866697A patent/IL128666A/xx not_active IP Right Cessation
- 1997-08-22 NZ NZ334256A patent/NZ334256A/xx unknown
- 1997-08-22 CN CN97198539A patent/CN1232451A/zh active Pending
- 1997-08-22 PL PL97331802A patent/PL331802A1/xx unknown
- 1997-08-22 CZ CZ99631A patent/CZ63199A3/cs unknown
- 1997-08-22 DE DE69716449T patent/DE69716449T2/de not_active Expired - Fee Related
- 1997-08-22 TR TR1999/00431T patent/TR199900431T2/xx unknown
- 1997-08-22 KR KR1019997001658A patent/KR100323272B1/ko not_active IP Right Cessation
- 1997-08-22 BR BR9713465-1A patent/BR9713465A/pt not_active Application Discontinuation
- 1997-08-22 SK SK250-99A patent/SK25099A3/sk unknown
- 1997-08-26 US US08/918,317 patent/US6417219B1/en not_active Expired - Fee Related
- 1997-08-27 CO CO97049510A patent/CO4900036A1/es unknown
- 1997-08-27 MY MYPI97003949A patent/MY116959A/en unknown
- 1997-08-27 ZA ZA9707698A patent/ZA977698B/xx unknown
- 1997-08-28 ID IDP972994A patent/ID18143A/id unknown
- 1997-08-28 PE PE1997000768A patent/PE109098A1/es not_active Application Discontinuation
1998
- 1998-02-03 TW TW087101301A patent/TWI232218B/zh not_active IP Right Cessation
1999
- 1999-02-23 NO NO19990855A patent/NO315371B1/no unknown
2000
- 2000-01-04 HK HK00100036A patent/HK1020962A1/xx not_active IP Right Cessation
2001
- 2001-06-25 US US09/888,759 patent/US20020072517A1/en not_active Abandoned
- 2001-06-25 US US09/888,675 patent/US6569855B2/en not_active Expired - Fee Related
2002
- 2002-12-03 US US10/308,780 patent/US6858628B2/en not_active Expired - Fee Related
2003
- 2003-11-13 JP JP2003384116A patent/JP2004115531A/ja not_active Withdrawn
2004
- 2004-12-03 US US11/003,594 patent/US20050101567A1/en not_active Abandoned
- 2004-12-03 US US11/003,884 patent/US20050154019A1/en not_active Abandoned

Also Published As

Publication number	Publication date
NO990855L (no)	1999-04-23
AU741893B2 (en)	2001-12-13
US20020061877A1 (en)	2002-05-23
PE109098A1 (es)	1999-02-19
EP0927161A1 (en)	1999-07-07
EP0927161B1 (en)	2002-10-16
KR100323272B1 (ko)	2002-02-06
CA2263928A1 (en)	1998-03-05
JP3541043B2 (ja)	2004-07-07
SK25099A3 (en)	2000-02-14
US20020072517A1 (en)	2002-06-13
US20030191163A1 (en)	2003-10-09
CZ63199A3 (cs)	1999-08-11
CO4900036A1 (es)	2000-03-27
AU4074197A (en)	1998-03-19
TWI232218B (en)	2005-05-11
NZ334256A (en)	2000-11-24
ATE226193T1 (de)	2002-11-15
RU2221782C2 (ru)	2004-01-20
HUP0000478A2 (hu)	2000-09-28
PT927161E (pt)	2003-12-31
IL128666A0 (en)	2000-01-31
JP2000516955A (ja)	2000-12-19
HUP0000478A3 (en)	2000-10-30
NO990855D0 (no)	1999-02-23
BR9713465A (pt)	2000-03-28
IL128666A (en)	2005-09-25
US20050101567A1 (en)	2005-05-12
ZA977698B (en)	1998-02-23
KR20000035922A (ko)	2000-06-26
CN1232451A (zh)	1999-10-20
ES2201318T3 (es)	2004-03-16
US6858628B2 (en)	2005-02-22
DE69716449D1 (de)	2002-11-21
US20050154019A1 (en)	2005-07-14
US6569855B2 (en)	2003-05-27
HK1020962A1 (en)	2000-05-26
PL331802A1 (en)	1999-08-02
WO1998008815A1 (en)	1998-03-05
ID18143A (id)	1998-03-05
US6417219B1 (en)	2002-07-09
JP2004115531A (ja)	2004-04-15
TR199900431T2 (xx)	1999-04-21
MY116959A (en)	2004-04-30
DE69716449T2 (de)	2003-08-07
DK0927161T3 (da)	2003-02-17

Publication	Publication Date	Title
NO315371B1 (no)	2003-08-25	Substituerte sykliske amin-metallprotease-inhibitorer
AU734834B2 (en)	2001-06-21	Heterocyclic metalloprotease inhibitors
US6218389B1 (en)	2001-04-17	Acyclic metalloprotease inhibitors
CA2263932A1 (en)	1998-03-05	1,4-heterocyclic metalloprotease inhibitors
NO315373B1 (no)	2003-08-25	Spirosykliske metallprotease-inhibitorer
NO315158B1 (no)	2003-07-21	1,3-diheterocykliske metalloprotease-inhibitorer
KR20010101735A (ko)	2001-11-14	아세틸렌 알파-아미노산계 설폰아미드 하이드록삼산티에이씨이 억제제
US6121272A (en)	2000-09-19	Bidentate metalloprotease inhibitors
MXPA01008855A (es)	2002-07-02	Inhibidores de metaloproteasa que contienen alquenilo y alquinilo.
KR20010101689A (ko)	2001-11-14	티에이씨이 억제제로서의 알키닐 함유 히드록삼산 화합물
US6872742B2 (en)	2005-03-29	Substituted cyclic amine metalloprotease inhibitors