NO313281B1 - Heteroarylsuccinamider og deres anvendelse for fremstilling av preparat som metalloproteinaseinhibitor - Google Patents
Heteroarylsuccinamider og deres anvendelse for fremstilling av preparat som metalloproteinaseinhibitor Download PDFInfo
- Publication number
- NO313281B1 NO313281B1 NO19991922A NO991922A NO313281B1 NO 313281 B1 NO313281 B1 NO 313281B1 NO 19991922 A NO19991922 A NO 19991922A NO 991922 A NO991922 A NO 991922A NO 313281 B1 NO313281 B1 NO 313281B1
- Authority
- NO
- Norway
- Prior art keywords
- phenyl
- formula
- alkyl
- pyrrol
- pharmaceutically acceptable
- Prior art date
Links
- 238000002360 preparation method Methods 0.000 title claims description 153
- 239000003475 metalloproteinase inhibitor Substances 0.000 title description 2
- 101710170181 Metalloproteinase inhibitor Proteins 0.000 title 1
- 229940126170 metalloproteinase inhibitor Drugs 0.000 title 1
- -1 oxo-substituted hexahydroazepine group Chemical group 0.000 claims description 204
- 150000001875 compounds Chemical class 0.000 claims description 171
- 239000002253 acid Substances 0.000 claims description 114
- JDVPQXZIJDEHAN-UHFFFAOYSA-N succinamic acid Chemical compound NC(=O)CCC(O)=O JDVPQXZIJDEHAN-UHFFFAOYSA-N 0.000 claims description 85
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 77
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 74
- 150000003839 salts Chemical class 0.000 claims description 44
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 35
- 239000000651 prodrug Substances 0.000 claims description 28
- 229940002612 prodrug Drugs 0.000 claims description 28
- 125000002883 imidazolyl group Chemical group 0.000 claims description 23
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 18
- 201000010099 disease Diseases 0.000 claims description 17
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 17
- 238000011282 treatment Methods 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 150000002367 halogens Chemical class 0.000 claims description 16
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 15
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
- 239000008194 pharmaceutical composition Substances 0.000 claims description 12
- 125000004076 pyridyl group Chemical group 0.000 claims description 12
- 239000012453 solvate Substances 0.000 claims description 12
- 239000003981 vehicle Substances 0.000 claims description 12
- 230000000694 effects Effects 0.000 claims description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 10
- 239000003085 diluting agent Substances 0.000 claims description 10
- 229910052757 nitrogen Inorganic materials 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- SNCZNSNPXMPCGN-UHFFFAOYSA-N butanediamide Chemical compound NC(=O)CCC(N)=O SNCZNSNPXMPCGN-UHFFFAOYSA-N 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000001072 heteroaryl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 6
- 125000002140 imidazol-4-yl group Chemical group [H]N1C([H])=NC([*])=C1[H] 0.000 claims description 5
- 230000001404 mediated effect Effects 0.000 claims description 5
- 201000008482 osteoarthritis Diseases 0.000 claims description 5
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 5
- 230000004614 tumor growth Effects 0.000 claims description 5
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 4
- 206010027476 Metastases Diseases 0.000 claims description 4
- 208000006011 Stroke Diseases 0.000 claims description 4
- 230000033115 angiogenesis Effects 0.000 claims description 4
- 208000007565 gingivitis Diseases 0.000 claims description 4
- 208000002780 macular degeneration Diseases 0.000 claims description 4
- 201000006417 multiple sclerosis Diseases 0.000 claims description 4
- 125000005188 oxoalkyl group Chemical group 0.000 claims description 4
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- 208000003120 Angiofibroma Diseases 0.000 claims description 3
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 3
- 208000022461 Glomerular disease Diseases 0.000 claims description 3
- 102000005741 Metalloproteases Human genes 0.000 claims description 3
- 108010006035 Metalloproteases Proteins 0.000 claims description 3
- 208000001132 Osteoporosis Diseases 0.000 claims description 3
- 230000003412 degenerative effect Effects 0.000 claims description 3
- 231100000852 glomerular disease Toxicity 0.000 claims description 3
- 201000011066 hemangioma Diseases 0.000 claims description 3
- 125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 claims description 3
- 201000001245 periodontitis Diseases 0.000 claims description 3
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 3
- 208000017520 skin disease Diseases 0.000 claims description 3
- OVBYHQYLZBBTHC-RGSZASNESA-N (3r)-4-[[(1r,2r)-2-hydroxy-2,3-dihydro-1h-inden-1-yl]amino]-4-oxo-3-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoic acid Chemical compound C=1N([C@H](CC(O)=O)C(=O)N[C@@H]2C3=CC=CC=C3C[C@H]2O)C=CC=1C(C=C1)=CC=C1C1=CC=NC=C1 OVBYHQYLZBBTHC-RGSZASNESA-N 0.000 claims description 2
- QTSOAJKHQODCIZ-JWQCQUIFSA-N (3r)-4-[[(1s)-2-hydroxy-1-phenylethyl]amino]-4-oxo-3-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoic acid Chemical compound C=1N([C@H](CC(O)=O)C(=O)N[C@H](CO)C=2C=CC=CC=2)C=CC=1C(C=C1)=CC=C1C1=CC=NC=C1 QTSOAJKHQODCIZ-JWQCQUIFSA-N 0.000 claims description 2
- 201000001320 Atherosclerosis Diseases 0.000 claims description 2
- 206010040943 Skin Ulcer Diseases 0.000 claims description 2
- 208000025865 Ulcer Diseases 0.000 claims description 2
- 230000036269 ulceration Effects 0.000 claims description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims 5
- ZGSXZKYHKNDSDE-IFMALSPDSA-N (3r)-4-[[(3s)-4,4-dimethyl-2-oxooxolan-3-yl]amino]-4-oxo-3-[3-(4-pyridin-4-ylphenyl)pyrrol-1-yl]butanoic acid Chemical compound CC1(C)COC(=O)[C@H]1NC(=O)[C@@H](CC(O)=O)N1C=C(C=2C=CC(=CC=2)C=2C=CN=CC=2)C=C1 ZGSXZKYHKNDSDE-IFMALSPDSA-N 0.000 claims 1
- ATTRSQMUDMGABC-FCHUYYIVSA-N (3s)-4-[[(2s)-1-hydroxy-3,3-dimethylbutan-2-yl]amino]-4-oxo-3-[1-(4-pyridin-4-ylphenyl)pyrrol-3-yl]butanoic acid Chemical compound C1=C([C@H](CC(O)=O)C(=O)N[C@H](CO)C(C)(C)C)C=CN1C1=CC=C(C=2C=CN=CC=2)C=C1 ATTRSQMUDMGABC-FCHUYYIVSA-N 0.000 claims 1
- UWDMKTDPDJCJOP-UHFFFAOYSA-N 4-hydroxy-2,2,6,6-tetramethylpiperidin-1-ium-4-carboxylate Chemical compound CC1(C)CC(O)(C(O)=O)CC(C)(C)N1 UWDMKTDPDJCJOP-UHFFFAOYSA-N 0.000 claims 1
- 208000024827 Alzheimer disease Diseases 0.000 claims 1
- 238000012512 characterization method Methods 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 230000009545 invasion Effects 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 245
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 229
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 227
- 238000000034 method Methods 0.000 description 166
- 239000007787 solid Substances 0.000 description 153
- 238000005481 NMR spectroscopy Methods 0.000 description 151
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical class C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 122
- 235000019439 ethyl acetate Nutrition 0.000 description 121
- 239000000203 mixture Substances 0.000 description 120
- 239000000243 solution Substances 0.000 description 112
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 82
- 238000006243 chemical reaction Methods 0.000 description 75
- 229910001868 water Inorganic materials 0.000 description 71
- 238000003818 flash chromatography Methods 0.000 description 69
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 68
- 238000000746 purification Methods 0.000 description 66
- 239000003480 eluent Substances 0.000 description 64
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 60
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 57
- 239000007858 starting material Substances 0.000 description 51
- 239000011734 sodium Substances 0.000 description 46
- 150000002148 esters Chemical class 0.000 description 45
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 44
- 239000003921 oil Substances 0.000 description 44
- 235000019198 oils Nutrition 0.000 description 44
- 235000002639 sodium chloride Nutrition 0.000 description 44
- 239000000047 product Substances 0.000 description 43
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 36
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 36
- 238000005160 1H NMR spectroscopy Methods 0.000 description 35
- 238000002844 melting Methods 0.000 description 35
- 230000008018 melting Effects 0.000 description 35
- ZLSTXEBTAJKDKH-UHFFFAOYSA-N benzyl 4-amino-4-oxobutanoate Chemical compound NC(=O)CCC(=O)OCC1=CC=CC=C1 ZLSTXEBTAJKDKH-UHFFFAOYSA-N 0.000 description 34
- 238000002000 high resolution fast-atom bombardment mass spectrometry Methods 0.000 description 34
- 239000012044 organic layer Substances 0.000 description 34
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 33
- 239000010410 layer Substances 0.000 description 32
- 102000002274 Matrix Metalloproteinases Human genes 0.000 description 30
- 108010000684 Matrix Metalloproteinases Proteins 0.000 description 30
- 229910004373 HOAc Inorganic materials 0.000 description 29
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 28
- 150000001412 amines Chemical class 0.000 description 28
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 27
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 27
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 27
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 24
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
- 230000008878 coupling Effects 0.000 description 23
- 238000010168 coupling process Methods 0.000 description 23
- 238000005859 coupling reaction Methods 0.000 description 23
- 229920006395 saturated elastomer Polymers 0.000 description 23
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 20
- 239000012267 brine Substances 0.000 description 20
- 239000008363 phosphate buffer Substances 0.000 description 20
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 20
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
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- 239000000843 powder Substances 0.000 description 19
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 18
- RROBIDXNTUAHFW-UHFFFAOYSA-N benzotriazol-1-yloxy-tris(dimethylamino)phosphanium Chemical compound C1=CC=C2N(O[P+](N(C)C)(N(C)C)N(C)C)N=NC2=C1 RROBIDXNTUAHFW-UHFFFAOYSA-N 0.000 description 18
- 239000001257 hydrogen Substances 0.000 description 18
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- 239000000725 suspension Substances 0.000 description 18
- 239000002904 solvent Substances 0.000 description 17
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 16
- 239000000706 filtrate Substances 0.000 description 16
- 239000003112 inhibitor Substances 0.000 description 16
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
- KMMJMRXVYSYXQC-UHFFFAOYSA-N 2,5-dimethoxy-3-(4-phenylphenyl)oxolane Chemical compound COC1OC(OC)CC1C1=CC=C(C=2C=CC=CC=2)C=C1 KMMJMRXVYSYXQC-UHFFFAOYSA-N 0.000 description 14
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 14
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- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 14
- VFRSADQPWYCXDG-LEUCUCNGSA-N ethyl (2s,5s)-5-methylpyrrolidine-2-carboxylate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.CCOC(=O)[C@@H]1CC[C@H](C)N1 VFRSADQPWYCXDG-LEUCUCNGSA-N 0.000 description 14
- 125000000623 heterocyclic group Chemical group 0.000 description 14
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
- 239000012317 TBTU Substances 0.000 description 13
- CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 13
- 239000002585 base Substances 0.000 description 13
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- 239000001384 succinic acid Substances 0.000 description 13
- KAJBMCZQVSQJDE-RXMQYKEDSA-N (2r)-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanedioic acid Chemical compound CC(C)(C)OC(=O)N[C@@H](C(O)=O)CC(O)=O KAJBMCZQVSQJDE-RXMQYKEDSA-N 0.000 description 12
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- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
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- 150000001345 alkine derivatives Chemical class 0.000 description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 11
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- 230000003197 catalytic effect Effects 0.000 description 11
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- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 10
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
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- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 7
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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 7
- BNKZAMCRVRPGCU-UHFFFAOYSA-N 2,5-dimethoxy-3-(4-phenylphenyl)-2,5-dihydrofuran Chemical compound COC1OC(OC)C(C=2C=CC(=CC=2)C=2C=CC=CC=2)=C1 BNKZAMCRVRPGCU-UHFFFAOYSA-N 0.000 description 6
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 6
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Classifications
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- 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
- C07D207/32—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/325—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals directly attached to the ring nitrogen atom
- C07D207/327—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- 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
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- 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
- C07D207/32—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/33—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 only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms with substituted hydrocarbon radicals, directly attached to ring carbon atoms
- C07D207/337—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
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- C07D231/12—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
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- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
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- C07D307/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
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US08/823,962 US6008243A (en) | 1996-10-24 | 1997-03-25 | Metalloproteinase inhibitors, pharmaceutical compositions containing them, and their use |
PCT/US1997/017809 WO1998017643A1 (en) | 1996-10-24 | 1997-10-06 | Heteroaryl succinamides and their use as metalloproteinase inhibitors |
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NO991922L NO991922L (no) | 1999-04-22 |
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NO19991922A NO313281B1 (no) | 1996-10-24 | 1999-04-22 | Heteroarylsuccinamider og deres anvendelse for fremstilling av preparat som metalloproteinaseinhibitor |
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US (1) | US6008243A (et) |
EP (1) | EP0937042A1 (et) |
JP (1) | JP2000511201A (et) |
KR (1) | KR20000052779A (et) |
CN (1) | CN1233237A (et) |
AP (1) | AP1360A (et) |
AR (1) | AR009124A1 (et) |
AU (1) | AU735194C (et) |
BG (1) | BG64506B1 (et) |
BR (1) | BR9713278A (et) |
CA (1) | CA2267879C (et) |
CZ (1) | CZ132199A3 (et) |
EA (1) | EA003127B1 (et) |
EE (1) | EE9900171A (et) |
GE (1) | GEP20012578B (et) |
IL (1) | IL128914A (et) |
IS (1) | IS5000A (et) |
NO (1) | NO313281B1 (et) |
NZ (1) | NZ334886A (et) |
OA (1) | OA11035A (et) |
PL (1) | PL332947A1 (et) |
SK (1) | SK48499A3 (et) |
TR (2) | TR199900874T2 (et) |
WO (1) | WO1998017643A1 (et) |
YU (1) | YU20199A (et) |
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1997
- 1997-03-25 US US08/823,962 patent/US6008243A/en not_active Expired - Fee Related
- 1997-10-06 SK SK484-99A patent/SK48499A3/sk unknown
- 1997-10-06 AU AU48060/97A patent/AU735194C/en not_active Ceased
- 1997-10-06 BR BR9713278-0A patent/BR9713278A/pt not_active Application Discontinuation
- 1997-10-06 JP JP10519394A patent/JP2000511201A/ja not_active Ceased
- 1997-10-06 TR TR1999/00874T patent/TR199900874T2/xx unknown
- 1997-10-06 CZ CZ991321A patent/CZ132199A3/cs unknown
- 1997-10-06 EE EEP199900171A patent/EE9900171A/et unknown
- 1997-10-06 YU YU20199A patent/YU20199A/sh unknown
- 1997-10-06 PL PL97332947A patent/PL332947A1/xx unknown
- 1997-10-06 GE GEAP19974822A patent/GEP20012578B/en unknown
- 1997-10-06 NZ NZ334886A patent/NZ334886A/xx unknown
- 1997-10-06 CN CN97198705A patent/CN1233237A/zh active Pending
- 1997-10-06 AP APAP/P/1999/001536A patent/AP1360A/en active
- 1997-10-06 EA EA199900366A patent/EA003127B1/ru not_active IP Right Cessation
- 1997-10-06 KR KR1019990703591A patent/KR20000052779A/ko not_active Application Discontinuation
- 1997-10-06 WO PCT/US1997/017809 patent/WO1998017643A1/en not_active Application Discontinuation
- 1997-10-06 EP EP97910770A patent/EP0937042A1/en not_active Withdrawn
- 1997-10-06 CA CA002267879A patent/CA2267879C/en not_active Expired - Fee Related
- 1997-10-06 IL IL12891497A patent/IL128914A/xx not_active IP Right Cessation
- 1997-10-06 TR TR2004/02157T patent/TR200402157T2/xx unknown
- 1997-10-23 AR ARP970104894A patent/AR009124A1/es unknown
-
1999
- 1999-03-12 IS IS5000A patent/IS5000A/is unknown
- 1999-04-16 OA OA9900084A patent/OA11035A/en unknown
- 1999-04-22 NO NO19991922A patent/NO313281B1/no not_active IP Right Cessation
- 1999-05-20 BG BG103415A patent/BG64506B1/bg unknown
Also Published As
Publication number | Publication date |
---|---|
EA003127B1 (ru) | 2003-02-27 |
IS5000A (is) | 1999-03-12 |
AP1360A (en) | 2005-01-05 |
BG103415A (en) | 2000-07-31 |
BG64506B1 (bg) | 2005-05-31 |
IL128914A0 (en) | 2000-02-17 |
CZ132199A3 (cs) | 1999-09-15 |
NO991922L (no) | 1999-04-22 |
AR009124A1 (es) | 2000-03-08 |
JP2000511201A (ja) | 2000-08-29 |
NZ334886A (en) | 2000-11-24 |
PL332947A1 (en) | 1999-10-25 |
AU735194C (en) | 2002-08-08 |
OA11035A (en) | 2002-03-06 |
TR199900874T2 (xx) | 1999-07-21 |
TR200402157T2 (tr) | 2005-02-21 |
EA199900366A1 (ru) | 1999-10-28 |
AU735194B2 (en) | 2001-07-05 |
YU20199A (sh) | 2001-09-28 |
GEP20012578B (en) | 2001-11-26 |
CA2267879C (en) | 2006-03-14 |
AP9901536A0 (en) | 1999-06-30 |
CN1233237A (zh) | 1999-10-27 |
CA2267879A1 (en) | 1998-04-30 |
NO991922D0 (no) | 1999-04-22 |
IL128914A (en) | 2003-04-10 |
WO1998017643A1 (en) | 1998-04-30 |
BR9713278A (pt) | 1999-11-03 |
KR20000052779A (ko) | 2000-08-25 |
EP0937042A1 (en) | 1999-08-25 |
EE9900171A (et) | 1999-12-15 |
AU4806097A (en) | 1998-05-15 |
SK48499A3 (en) | 2000-04-10 |
US6008243A (en) | 1999-12-28 |
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MM1K | Lapsed by not paying the annual fees |