NO312416B1 - Sulfonsyre- eller sulfonylamino-N-(heteroaralkyl)- azaheterocyklylamidforbindelser - Google Patents
Sulfonsyre- eller sulfonylamino-N-(heteroaralkyl)- azaheterocyklylamidforbindelser Download PDFInfo
- Publication number
- NO312416B1 NO312416B1 NO19992853A NO992853A NO312416B1 NO 312416 B1 NO312416 B1 NO 312416B1 NO 19992853 A NO19992853 A NO 19992853A NO 992853 A NO992853 A NO 992853A NO 312416 B1 NO312416 B1 NO 312416B1
- Authority
- NO
- Norway
- Prior art keywords
- sulfonic acid
- oxopyrrolidin
- ylmethyl
- methoxynaphthalene
- chloro
- Prior art date
Links
- 150000001875 compounds Chemical class 0.000 title claims description 369
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 title description 2
- 125000004475 heteroaralkyl group Chemical group 0.000 title 1
- 150000003839 salts Chemical class 0.000 claims description 48
- 229910052739 hydrogen Inorganic materials 0.000 claims description 47
- 229910052757 nitrogen Inorganic materials 0.000 claims description 47
- 108010074860 Factor Xa Proteins 0.000 claims description 33
- 230000000694 effects Effects 0.000 claims description 27
- -1 dihydroquinolyl Chemical group 0.000 claims description 26
- 239000003146 anticoagulant agent Substances 0.000 claims description 23
- 208000007536 Thrombosis Diseases 0.000 claims description 19
- 230000015572 biosynthetic process Effects 0.000 claims description 17
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
- 238000002560 therapeutic procedure Methods 0.000 claims description 14
- 230000002792 vascular Effects 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 11
- 210000001367 artery Anatomy 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 10
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 210000003462 vein Anatomy 0.000 claims description 9
- 230000001154 acute effect Effects 0.000 claims description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 8
- 208000035475 disorder Diseases 0.000 claims description 7
- 206010000891 acute myocardial infarction Diseases 0.000 claims description 6
- 238000007887 coronary angioplasty Methods 0.000 claims description 6
- 229910052736 halogen Inorganic materials 0.000 claims description 6
- VFHQLCGAUYJSRP-FERBBOLQSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2SC(S(=O)(=O)N[C@H]3CCN(C3=O)CC3=CC=C4C=CN=C(C4=C3)N)=CC2=C1 VFHQLCGAUYJSRP-FERBBOLQSA-N 0.000 claims description 6
- WNQJRFJOLDUOFH-FERBBOLQSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-6-chloro-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C=C2SC(S(=O)(=O)N[C@H]3CCN(C3=O)CC3=CC=C4C=CN=C(C4=C3)N)=CC2=C1 WNQJRFJOLDUOFH-FERBBOLQSA-N 0.000 claims description 6
- MMPKCFIXJKMLPC-FTBISJDPSA-N n-[(3s)-1-[(2-aminoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC(N)=NC2=CC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 MMPKCFIXJKMLPC-FTBISJDPSA-N 0.000 claims description 6
- 230000001575 pathological effect Effects 0.000 claims description 6
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- 125000005493 quinolyl group Chemical group 0.000 claims description 6
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- GNSUPVVLHBGDAU-QHCPKHFHSA-N 7-methoxy-n-[(3s)-2-oxo-1-[(2-oxo-1h-quinolin-6-yl)methyl]pyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound N1=C(O)C=CC2=CC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 GNSUPVVLHBGDAU-QHCPKHFHSA-N 0.000 claims description 5
- WJDBPMVSXWUXAW-DEOSSOPVSA-N 7-methoxy-n-methyl-n-[(3s)-2-oxo-1-[(2-oxo-1h-quinolin-5-yl)methyl]pyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound N1C(=O)C=CC2=C1C=CC=C2CN(C1=O)CC[C@@H]1N(C)S(=O)(=O)C1=CC2=CC(OC)=CC=C2C=C1 WJDBPMVSXWUXAW-DEOSSOPVSA-N 0.000 claims description 5
- 206010053567 Coagulopathies Diseases 0.000 claims description 5
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 claims description 5
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- 125000005945 imidazopyridyl group Chemical group 0.000 claims description 5
- 230000002401 inhibitory effect Effects 0.000 claims description 5
- 125000005956 isoquinolyl group Chemical group 0.000 claims description 5
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- VCVKZPRYRNNAHF-FYZYNONXSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-5-pyridin-3-ylthiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@H]1CCN(C1=O)CC1=CC=C2C=CN=C(C2=C1)N)S(=O)(=O)C(S1)=CC=C1C1=CC=CN=C1 VCVKZPRYRNNAHF-FYZYNONXSA-N 0.000 claims description 5
- CDIMXWPYBBXLPZ-FYZYNONXSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-5-pyridin-4-ylthiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N([C@H]1CCN(C1=O)CC1=CC=C2C=CN=C(C2=C1)N)S(=O)(=O)C(S1)=CC=C1C1=CC=NC=C1 CDIMXWPYBBXLPZ-FYZYNONXSA-N 0.000 claims description 5
- XQYHQVFBDDWDCG-BQAIUKQQSA-N n-[(3s)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CN=C(N)C2=CC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 XQYHQVFBDDWDCG-BQAIUKQQSA-N 0.000 claims description 5
- SEYWMQRAUGNBSI-LMOVPXPDSA-N n-[(3s)-1-[(2-aminoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-6-chloro-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C(Cl)C=C2SC(S(=O)(=O)N[C@H]3CCN(C3=O)CC=3C=CC4=CC=C(N=C4C=3)N)=CC2=C1 SEYWMQRAUGNBSI-LMOVPXPDSA-N 0.000 claims description 5
- KHZHBQZHEIZBHY-FYZYNONXSA-N n-[(3s)-1-[(4-aminoquinolin-6-yl)methyl]-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2SC(S(=O)(=O)N[C@H]3CCN(C3=O)CC3=CC=C4N=CC=C(C4=C3)N)=CC2=C1 KHZHBQZHEIZBHY-FYZYNONXSA-N 0.000 claims description 5
- 239000008194 pharmaceutical composition Substances 0.000 claims description 5
- 125000006085 pyrrolopyridyl group Chemical group 0.000 claims description 5
- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 claims description 5
- 208000037803 restenosis Diseases 0.000 claims description 5
- 230000002537 thrombolytic effect Effects 0.000 claims description 5
- 210000005166 vasculature Anatomy 0.000 claims description 5
- DCVXLCIPWIKDJU-BOXHHOBZSA-N 7-methoxy-n-[(3s)-2-oxo-1-(1h-pyrrolo[3,2-b]pyridin-2-ylmethyl)pyrrolidin-3-yl]naphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2NC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC2=N1 DCVXLCIPWIKDJU-BOXHHOBZSA-N 0.000 claims description 4
- JAEKEOJFYOBMBH-DEOSSOPVSA-N 7-methoxy-n-methyl-n-[(3s)-2-oxo-1-[(2-oxo-1h-quinolin-7-yl)methyl]pyrrolidin-3-yl]naphthalene-2-sulfonamide Chemical compound C1=CC(=O)NC2=CC(CN3CC[C@@H](C3=O)N(C)S(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 JAEKEOJFYOBMBH-DEOSSOPVSA-N 0.000 claims description 4
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- XQYHQVFBDDWDCG-GNAFDRTKSA-N n-[(3r)-1-[(1-aminoisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CN=C(N)C2=CC(CN3CC[C@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 XQYHQVFBDDWDCG-GNAFDRTKSA-N 0.000 claims description 4
- MGBXCZRURZLLGG-BOXHHOBZSA-N n-[(3s)-1-(3h-benzimidazol-5-ylmethyl)-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=C2NC=NC2=CC(CN2CC[C@@H](C2=O)NS(=O)(=O)C=2C=CC3=CC=C(C=C3C=2)OC)=C1 MGBXCZRURZLLGG-BOXHHOBZSA-N 0.000 claims description 4
- HZBSKFFTPFUHBU-BQAIUKQQSA-N n-[(3s)-1-[(1-amino-6-methoxyisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide;hydrochloride Chemical compound Cl.N1=CC=C2C=C(OC)C(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC2=C1N HZBSKFFTPFUHBU-BQAIUKQQSA-N 0.000 claims description 4
- QTMHKYIZBVUMKD-QHCPKHFHSA-N n-[(3s)-1-[(2-aminoquinolin-6-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxynaphthalene-2-sulfonamide Chemical compound N1=C(N)C=CC2=CC(CN3CC[C@@H](C3=O)NS(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 QTMHKYIZBVUMKD-QHCPKHFHSA-N 0.000 claims description 4
- QFZAMTBGXXFFQX-LMOVPXPDSA-N n-[(3s)-1-[(2-aminoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2SC(S(=O)(=O)N[C@H]3CCN(C3=O)CC=3C=CC4=CC=C(N=C4C=3)N)=CC2=C1 QFZAMTBGXXFFQX-LMOVPXPDSA-N 0.000 claims description 4
- PXHFGDWQPIVXFA-BQAIUKQQSA-N n-[(3s)-1-[(4-aminoquinazolin-6-yl)methyl]-2-oxopyrrolidin-3-yl]-7-methoxy-n-methylnaphthalene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.N1=CN=C(N)C2=CC(CN3CC[C@@H](C3=O)N(C)S(=O)(=O)C=3C=CC4=CC=C(C=C4C=3)OC)=CC=C21 PXHFGDWQPIVXFA-BQAIUKQQSA-N 0.000 claims description 4
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 4
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- RROZPQBCANKSJH-GXKRWWSZSA-N (3S)-1-[(1-aminoisoquinolin-7-yl)methyl]-3-(methylamino)pyrrolidin-2-one 7-methoxynaphthalene-2-sulfonic acid 2,2,2-trifluoroacetic acid Chemical compound CN[C@@H](CCN1CC2=CC=C(C=CN=C3N)C3=C2)C1=O.COC1=CC=C(C=CC(S(O)(=O)=O)=C2)C2=C1.OC(C(F)(F)F)=O RROZPQBCANKSJH-GXKRWWSZSA-N 0.000 claims description 3
- IJZYUSAXPDDIKX-HNNXBMFYSA-N 6-chloro-n-[(3s)-1-(furo[3,2-b]pyridin-2-ylmethyl)-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound C1=CC=C2OC(CN3CC[C@@H](C3=O)NS(=O)(=O)C3=CC4=CC=C(C=C4S3)Cl)=CC2=N1 IJZYUSAXPDDIKX-HNNXBMFYSA-N 0.000 claims description 3
- ROMBXSYEYVFYBT-INIZCTEOSA-N 6-chloro-n-[(3s)-1-[(4-chloro-1h-pyrrolo[3,2-c]pyridin-2-yl)methyl]-2-oxopyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide Chemical compound N1=CC=C2NC(CN3CC[C@@H](C3=O)NS(=O)(=O)C3=CC4=CC=C(C=C4S3)Cl)=CC2=C1Cl ROMBXSYEYVFYBT-INIZCTEOSA-N 0.000 claims description 3
- FCKLLRUYGATBJZ-NTISSMGPSA-N 6-chloro-n-[(3s)-2-oxo-1-(1h-pyrrolo[2,3-c]pyridin-2-ylmethyl)pyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=NC=C2NC(CN3CC[C@@H](C3=O)NS(=O)(=O)C3=CC4=CC=C(C=C4S3)Cl)=CC2=C1 FCKLLRUYGATBJZ-NTISSMGPSA-N 0.000 claims description 3
- MOPNSDIFLDWQAX-NTISSMGPSA-N 6-chloro-n-[(3s)-2-oxo-1-(1h-pyrrolo[3,2-b]pyridin-2-ylmethyl)pyrrolidin-3-yl]-1-benzothiophene-2-sulfonamide;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.C1=CC=C2NC(CN3CC[C@@H](C3=O)NS(=O)(=O)C3=CC4=CC=C(C=C4S3)Cl)=CC2=N1 MOPNSDIFLDWQAX-NTISSMGPSA-N 0.000 claims description 3
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- 235000010288 sodium nitrite Nutrition 0.000 description 1
- IGESERIYEHZBPY-UHFFFAOYSA-M sodium;7-methoxynaphthalene-2-sulfonate Chemical compound [Na+].C1=CC(S([O-])(=O)=O)=CC2=CC(OC)=CC=C21 IGESERIYEHZBPY-UHFFFAOYSA-M 0.000 description 1
- 239000008247 solid mixture Substances 0.000 description 1
- 238000012453 sprague-dawley rat model Methods 0.000 description 1
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- 229910001220 stainless steel Inorganic materials 0.000 description 1
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- 238000010561 standard procedure Methods 0.000 description 1
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- 230000036262 stenosis Effects 0.000 description 1
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- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
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- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 description 1
- BECQKEJNGIMSSG-IBGZPJMESA-N tert-butyl 2-[[(3s)-3-[(6-chloro-1-benzothiophen-2-yl)sulfonylamino]-2-oxopyrrolidin-1-yl]methyl]pyrrolo[2,3-c]pyridine-1-carboxylate Chemical compound C1=NC=C2N(C(=O)OC(C)(C)C)C(CN3C([C@@H](NS(=O)(=O)C=4SC5=CC(Cl)=CC=C5C=4)CC3)=O)=CC2=C1 BECQKEJNGIMSSG-IBGZPJMESA-N 0.000 description 1
- BNWCETAHAJSBFG-UHFFFAOYSA-N tert-butyl 2-bromoacetate Chemical compound CC(C)(C)OC(=O)CBr BNWCETAHAJSBFG-UHFFFAOYSA-N 0.000 description 1
- FUKNUVWILSPUSJ-UHFFFAOYSA-N tert-butyl n-(4-iodopyridin-3-yl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CN=CC=C1I FUKNUVWILSPUSJ-UHFFFAOYSA-N 0.000 description 1
- ZJXGXLAOYWYMCQ-HNNXBMFYSA-N tert-butyl n-[(3s)-1-[(1-amino-6-methoxyisoquinolin-7-yl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound COC1=CC2=CC=NC(N)=C2C=C1CN1CC[C@H](NC(=O)OC(C)(C)C)C1=O ZJXGXLAOYWYMCQ-HNNXBMFYSA-N 0.000 description 1
- HKSOXCDXUDXKCF-HNNXBMFYSA-N tert-butyl n-[(3s)-1-[(2-chloroquinolin-5-yl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CC=CC2=NC(Cl)=CC=C12 HKSOXCDXUDXKCF-HNNXBMFYSA-N 0.000 description 1
- RFMPJYFOJBRPQN-HNNXBMFYSA-N tert-butyl n-[(3s)-1-[(2-chloroquinolin-6-yl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CC=C(N=C(Cl)C=C2)C2=C1 RFMPJYFOJBRPQN-HNNXBMFYSA-N 0.000 description 1
- UDPQZCMVNDMLAU-LBPRGKRZSA-N tert-butyl n-[(3s)-1-[(7-chlorothieno[2,3-c]pyridin-3-yl)methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CSC2=C(Cl)N=CC=C12 UDPQZCMVNDMLAU-LBPRGKRZSA-N 0.000 description 1
- XDWCTOGIJLPLAB-AWEZNQCLSA-N tert-butyl n-[(3s)-1-[2-(4-nitrophenyl)ethyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CCC1=CC=C([N+]([O-])=O)C=C1 XDWCTOGIJLPLAB-AWEZNQCLSA-N 0.000 description 1
- JEQCOMGANLGZGA-SFHVURJKSA-N tert-butyl n-[(3s)-1-[[1-(benzenesulfonyl)-4-chloropyrrolo[3,2-c]pyridin-2-yl]methyl]-2-oxopyrrolidin-3-yl]carbamate Chemical compound O=C1[C@@H](NC(=O)OC(C)(C)C)CCN1CC1=CC2=C(Cl)N=CC=C2N1S(=O)(=O)C1=CC=CC=C1 JEQCOMGANLGZGA-SFHVURJKSA-N 0.000 description 1
- WKHGDPZRLXDVMJ-UHFFFAOYSA-N tert-butyl n-pyridin-3-ylcarbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=CN=C1 WKHGDPZRLXDVMJ-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- DBDCNCCRPKTRSD-UHFFFAOYSA-N thieno[3,2-b]pyridine Chemical compound C1=CC=C2SC=CC2=N1 DBDCNCCRPKTRSD-UHFFFAOYSA-N 0.000 description 1
- KHXSHOAPGUCQLC-UHFFFAOYSA-N thieno[3,2-b]pyridine-2-sulfonyl chloride Chemical compound C1=CC=C2SC(S(=O)(=O)Cl)=CC2=N1 KHXSHOAPGUCQLC-UHFFFAOYSA-N 0.000 description 1
- 230000002885 thrombogenetic effect Effects 0.000 description 1
- 239000002396 thromboxane receptor blocking agent Substances 0.000 description 1
- 238000004448 titration Methods 0.000 description 1
- 210000003437 trachea Anatomy 0.000 description 1
- 230000000472 traumatic effect Effects 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 229960001322 trypsin Drugs 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 210000002268 wool Anatomy 0.000 description 1
- UGZADUVQMDAIAO-UHFFFAOYSA-L zinc hydroxide Chemical compound [OH-].[OH-].[Zn+2] UGZADUVQMDAIAO-UHFFFAOYSA-L 0.000 description 1
- 229910021511 zinc hydroxide Inorganic materials 0.000 description 1
- 229940007718 zinc hydroxide Drugs 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- 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
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/4164—1,3-Diazoles
- A61K31/4184—1,3-Diazoles condensed with carbocyclic rings, e.g. benzimidazoles
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4365—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system having sulfur as a ring hetero atom, e.g. ticlopidine
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
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- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/02—Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/06—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
- C07D409/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- 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
- C07D491/02—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 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Hematology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (2)
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US3315996P | 1996-12-13 | 1996-12-13 | |
PCT/US1997/022406 WO1998025611A1 (en) | 1996-12-13 | 1997-12-03 | Sulfonic acid or sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds |
Publications (3)
Publication Number | Publication Date |
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NO992853D0 NO992853D0 (no) | 1999-06-11 |
NO992853L NO992853L (no) | 1999-08-10 |
NO312416B1 true NO312416B1 (no) | 2002-05-06 |
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NO19992853A NO312416B1 (no) | 1996-12-13 | 1999-06-11 | Sulfonsyre- eller sulfonylamino-N-(heteroaralkyl)- azaheterocyklylamidforbindelser |
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EP (1) | EP0944386B1 (pt) |
JP (1) | JP4223560B2 (pt) |
KR (1) | KR20000057528A (pt) |
CN (1) | CN1244798A (pt) |
AP (1) | AP1032A (pt) |
AT (1) | ATE224192T1 (pt) |
AU (1) | AU726637B2 (pt) |
BG (1) | BG103558A (pt) |
BR (1) | BR9713921A (pt) |
CA (1) | CA2274686C (pt) |
DE (1) | DE69715658T2 (pt) |
DK (1) | DK0944386T3 (pt) |
EA (1) | EA002817B1 (pt) |
ES (1) | ES2184145T3 (pt) |
HU (1) | HUP9904188A3 (pt) |
IL (1) | IL130152A0 (pt) |
NO (1) | NO312416B1 (pt) |
OA (1) | OA11062A (pt) |
PL (1) | PL333921A1 (pt) |
PT (1) | PT944386E (pt) |
SK (1) | SK71299A3 (pt) |
WO (1) | WO1998025611A1 (pt) |
ZA (1) | ZA9711207B (pt) |
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US6602864B1 (en) * | 1996-12-13 | 2003-08-05 | Aventis Pharma Deutschland Gmbh | Sulfonic acid or sulfonylamino N-(heteroaralkyl)-azaheterocyclylamide compounds |
US6281227B1 (en) * | 1996-12-13 | 2001-08-28 | Aventis Pharma Deutschland Gmbh | Sulfonic acid sulfonylamino n-(heteroaralkyl)-azaheterocyclylamide compounds |
IL123986A (en) * | 1997-04-24 | 2011-10-31 | Organon Nv | Medicinal compounds |
AR016817A1 (es) * | 1997-08-14 | 2001-08-01 | Smithkline Beecham Plc | Derivados de fenilurea o feniltiourea, procedimiento para su preparacion, coleccion de compuestos, compuestos intermediarios, composicion farmaceutica,metodo de tratamiento y uso de dichos compuestos para la manufactura de un medicamento |
EP1009758B1 (en) | 1997-08-29 | 2005-06-01 | Tularik Limited | Meta-benzamidine derivatives as serine protease inhibitors |
BR9815377A (pt) | 1997-09-30 | 2001-01-16 | Daiichi Pharmaceutical Co Ltda | Derivados de sulfonil |
EP1065200A4 (en) | 1998-03-19 | 2003-01-02 | Ajinomoto Kk | Aminoisoquinoline DERIVATIVES |
AU5196399A (en) * | 1998-08-11 | 2000-03-06 | Daiichi Pharmaceutical Co., Ltd. | Novel sulfonyl derivatives |
CA2408913A1 (en) * | 2000-05-16 | 2001-11-22 | Takeda Chemical Industries, Ltd. | Melanin-concentrating hormone antagonist |
GB0114005D0 (en) | 2001-06-08 | 2001-08-01 | Glaxo Group Ltd | Chemical compounds |
GB0114004D0 (en) | 2001-06-08 | 2001-08-01 | Glaxo Group Ltd | Chemical compounds |
GB0127568D0 (en) | 2001-11-16 | 2002-01-09 | Glaxo Group Ltd | Chemical compounds |
AU2003232173A1 (en) * | 2002-06-12 | 2003-12-31 | Qsi Pharma A/S | Compounds and methods for controlling bacterial virulence |
EP2982668A3 (en) | 2002-12-03 | 2016-04-13 | Pharmacyclics LLC | 2-(2-hydroxybiphenyl-3-yl)-1h-benzoimidazole-5-carboxamidine derivatives as factor viia inhibitors for the treatment of thromboembolic disorders |
JP2008509222A (ja) * | 2004-08-09 | 2008-03-27 | グラクソ グループ リミテッド | 抗菌剤 |
FR2890072A1 (fr) | 2005-09-01 | 2007-03-02 | Fournier S A Sa Lab | Nouveaux composesde pyrrolopyridine |
US8143285B2 (en) * | 2005-09-06 | 2012-03-27 | Shionogi & Co., Ltd. | Indolecarboxylic acid derivative having PGD2 receptor antagonistic activity |
FR2955110A1 (fr) | 2010-01-08 | 2011-07-15 | Fournier Lab Sa | Nouveaux derives de type pyrrolopyridine benzoique |
EP2606893A1 (en) | 2011-12-21 | 2013-06-26 | Sanofi | Sulphonylaminopyrrolidinone derivatives, their preparation and their therapeutic application |
CN104098497B (zh) * | 2014-06-17 | 2016-04-13 | 王庚禹 | 一种新的酰胺类化合物 |
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DE4121947A1 (de) * | 1991-07-03 | 1993-01-07 | Basf Ag | 2-(3-(4-amidino-phenyl))-propionsaeurederivate, ihre herstellung und verwendung |
JPH10503176A (ja) * | 1994-06-17 | 1998-03-24 | コーバス インターナショナル, インコーポレイテッド | 酵素インヒビターとしての3−アミノ−2−オキソ−1−ピペリジン酢酸誘導体 |
US5612353A (en) * | 1995-06-07 | 1997-03-18 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Substituted (sulfinic acid, sulfonic acid, sulfonylamino or sulfinylamino) N-[(aminoiminomethyl)phenylalkyl]-azaheterocyclylamide compounds |
-
1997
- 1997-12-03 ES ES97951573T patent/ES2184145T3/es not_active Expired - Lifetime
- 1997-12-03 DE DE69715658T patent/DE69715658T2/de not_active Expired - Lifetime
- 1997-12-03 SK SK712-99A patent/SK71299A3/sk unknown
- 1997-12-03 CN CN97181387A patent/CN1244798A/zh active Pending
- 1997-12-03 EA EA199900542A patent/EA002817B1/ru not_active IP Right Cessation
- 1997-12-03 IL IL13015297A patent/IL130152A0/xx unknown
- 1997-12-03 PL PL97333921A patent/PL333921A1/xx unknown
- 1997-12-03 BR BR9713921A patent/BR9713921A/pt not_active IP Right Cessation
- 1997-12-03 AP APAP/P/1999/001552A patent/AP1032A/en active
- 1997-12-03 KR KR1019990705236A patent/KR20000057528A/ko not_active Application Discontinuation
- 1997-12-03 CA CA002274686A patent/CA2274686C/en not_active Expired - Fee Related
- 1997-12-03 PT PT97951573T patent/PT944386E/pt unknown
- 1997-12-03 AU AU55182/98A patent/AU726637B2/en not_active Ceased
- 1997-12-03 EP EP97951573A patent/EP0944386B1/en not_active Expired - Lifetime
- 1997-12-03 WO PCT/US1997/022406 patent/WO1998025611A1/en not_active Application Discontinuation
- 1997-12-03 DK DK97951573T patent/DK0944386T3/da active
- 1997-12-03 AT AT97951573T patent/ATE224192T1/de not_active IP Right Cessation
- 1997-12-03 HU HU9904188A patent/HUP9904188A3/hu unknown
- 1997-12-03 JP JP52684498A patent/JP4223560B2/ja not_active Expired - Fee Related
- 1997-12-12 ZA ZA9711207A patent/ZA9711207B/xx unknown
-
1999
- 1999-06-11 OA OA9900124A patent/OA11062A/en unknown
- 1999-06-11 NO NO19992853A patent/NO312416B1/no unknown
- 1999-07-07 BG BG103558A patent/BG103558A/xx unknown
Also Published As
Publication number | Publication date |
---|---|
EP0944386A4 (en) | 2001-04-11 |
EP0944386B1 (en) | 2002-09-18 |
AU5518298A (en) | 1998-07-03 |
HUP9904188A3 (en) | 2003-02-28 |
CN1244798A (zh) | 2000-02-16 |
JP4223560B2 (ja) | 2009-02-12 |
EA199900542A1 (ru) | 2000-02-28 |
NO992853D0 (no) | 1999-06-11 |
ATE224192T1 (de) | 2002-10-15 |
JP2001506630A (ja) | 2001-05-22 |
ZA9711207B (en) | 1998-07-20 |
DK0944386T3 (da) | 2003-01-27 |
SK71299A3 (en) | 2000-12-11 |
KR20000057528A (ko) | 2000-09-25 |
NO992853L (no) | 1999-08-10 |
IL130152A0 (en) | 2000-06-01 |
PT944386E (pt) | 2003-01-31 |
HUP9904188A1 (hu) | 2000-06-28 |
BR9713921A (pt) | 2000-03-21 |
CA2274686A1 (en) | 1998-06-18 |
AP9901552A0 (en) | 1999-06-30 |
OA11062A (en) | 2002-03-11 |
CA2274686C (en) | 2009-02-03 |
PL333921A1 (en) | 2000-01-31 |
AP1032A (en) | 2001-12-24 |
BG103558A (en) | 2000-04-28 |
EP0944386A1 (en) | 1999-09-29 |
ES2184145T3 (es) | 2003-04-01 |
DE69715658T2 (de) | 2003-05-22 |
DE69715658D1 (de) | 2002-10-24 |
WO1998025611A1 (en) | 1998-06-18 |
EA002817B1 (ru) | 2002-10-31 |
AU726637B2 (en) | 2000-11-16 |
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