SK9192000A3 - Integrin receptor antagonists - Google Patents
Integrin receptor antagonists Download PDFInfo
- Publication number
- SK9192000A3 SK9192000A3 SK919-2000A SK9192000A SK9192000A3 SK 9192000 A3 SK9192000 A3 SK 9192000A3 SK 9192000 A SK9192000 A SK 9192000A SK 9192000 A3 SK9192000 A3 SK 9192000A3
- Authority
- SK
- Slovakia
- Prior art keywords
- alkyl
- aryl
- naphthyridin
- tetrahydro
- nonanoic acid
- Prior art date
Links
- 229940127449 Integrin Receptor Antagonists Drugs 0.000 title claims abstract description 19
- 150000001875 compounds Chemical class 0.000 claims abstract description 77
- 102000006495 integrins Human genes 0.000 claims abstract description 61
- 108010044426 integrins Proteins 0.000 claims abstract description 61
- 208000006386 Bone Resorption Diseases 0.000 claims abstract description 30
- 230000024279 bone resorption Effects 0.000 claims abstract description 30
- 230000004614 tumor growth Effects 0.000 claims abstract description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 23
- 206010061218 Inflammation Diseases 0.000 claims abstract description 22
- 201000010099 disease Diseases 0.000 claims abstract description 22
- 230000004054 inflammatory process Effects 0.000 claims abstract description 22
- 206010027476 Metastases Diseases 0.000 claims abstract description 21
- 230000033115 angiogenesis Effects 0.000 claims abstract description 21
- 230000009401 metastasis Effects 0.000 claims abstract description 21
- 206010012689 Diabetic retinopathy Diseases 0.000 claims abstract description 19
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 19
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 18
- 208000037803 restenosis Diseases 0.000 claims abstract description 18
- 230000003612 virological effect Effects 0.000 claims abstract description 15
- 239000005557 antagonist Substances 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 608
- 125000003118 aryl group Chemical group 0.000 claims description 352
- -1 amino, amino Chemical group 0.000 claims description 213
- 239000000203 mixture Substances 0.000 claims description 121
- 125000001424 substituent group Chemical group 0.000 claims description 66
- 229910052739 hydrogen Inorganic materials 0.000 claims description 64
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 62
- 239000001257 hydrogen Substances 0.000 claims description 58
- 229910052799 carbon Inorganic materials 0.000 claims description 57
- 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 53
- XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 50
- 125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 49
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 48
- 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 47
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 44
- 239000000126 substance Substances 0.000 claims description 43
- 229940044551 receptor antagonist Drugs 0.000 claims description 40
- 239000002464 receptor antagonist Substances 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 40
- 239000002253 acid Substances 0.000 claims description 39
- 125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 39
- 150000002148 esters Chemical class 0.000 claims description 39
- 125000003545 alkoxy group Chemical group 0.000 claims description 33
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 33
- 230000003042 antagnostic effect Effects 0.000 claims description 33
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 32
- FBUKVWPVBMHYJY-UHFFFAOYSA-N nonanoic acid Chemical compound CCCCCCCCC(O)=O FBUKVWPVBMHYJY-UHFFFAOYSA-N 0.000 claims description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 30
- 125000004432 carbon atom Chemical group C* 0.000 claims description 29
- 150000002431 hydrogen Chemical class 0.000 claims description 29
- ORTFAQDWJHRMNX-UHFFFAOYSA-N hydroxidooxidocarbon(.) Chemical group O[C]=O ORTFAQDWJHRMNX-UHFFFAOYSA-N 0.000 claims description 28
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 26
- 239000008194 pharmaceutical composition Substances 0.000 claims description 26
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
- 241000124008 Mammalia Species 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 23
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 21
- 125000005842 heteroatom Chemical group 0.000 claims description 21
- 239000003795 chemical substances by application Substances 0.000 claims description 20
- 125000004657 aryl sulfonyl amino group Chemical group 0.000 claims description 19
- 229910052757 nitrogen Inorganic materials 0.000 claims description 19
- 230000005764 inhibitory process Effects 0.000 claims description 18
- 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 17
- 150000002367 halogens Chemical class 0.000 claims description 17
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 16
- 125000004658 aryl carbonyl amino group Chemical group 0.000 claims description 15
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 15
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 15
- 239000003814 drug Substances 0.000 claims description 15
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 15
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 14
- 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 14
- 235000019260 propionic acid Nutrition 0.000 claims description 14
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
- 230000000694 effects Effects 0.000 claims description 13
- 229910052760 oxygen Inorganic materials 0.000 claims description 12
- 229940122361 Bisphosphonate Drugs 0.000 claims description 11
- 125000005100 aryl amino carbonyl group Chemical group 0.000 claims description 11
- 150000004663 bisphosphonates Chemical class 0.000 claims description 11
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 11
- 125000004103 aminoalkyl group Chemical group 0.000 claims description 10
- 239000003937 drug carrier Substances 0.000 claims description 10
- 230000030991 negative regulation of bone resorption Effects 0.000 claims description 10
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
- 239000004480 active ingredient Substances 0.000 claims description 9
- 125000004442 acylamino group Chemical group 0.000 claims description 9
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 9
- 125000005162 aryl oxy carbonyl amino group Chemical group 0.000 claims description 9
- 125000005605 benzo group Chemical group 0.000 claims description 9
- 230000009977 dual effect Effects 0.000 claims description 9
- 239000000463 material Substances 0.000 claims description 9
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 9
- 125000004043 oxo group Chemical group O=* 0.000 claims description 9
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 9
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 8
- 239000003112 inhibitor Substances 0.000 claims description 8
- 125000003367 polycyclic group Polymers 0.000 claims description 8
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 7
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 claims description 7
- 125000004429 atom Chemical group 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 230000001404 mediated effect Effects 0.000 claims description 7
- YICWVYSPJDTUBI-IBGZPJMESA-N (2s)-2-pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1([C@H](CCCCCCCC=2N=C3NCCCC3=CC=2)C(=O)O)=CN=CN=C1 YICWVYSPJDTUBI-IBGZPJMESA-N 0.000 claims description 6
- JTWYZWVIMIDABC-SFHVURJKSA-N (3s)-3-pyridin-3-yl-3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]propanoic acid Chemical compound C1([C@@H](NC(=O)CCCCC=2N=C3NCCCC3=CC=2)CC(=O)O)=CC=CN=C1 JTWYZWVIMIDABC-SFHVURJKSA-N 0.000 claims description 6
- DSVRSYVZAMHQET-QFIPXVFZSA-N (3s)-3-quinolin-3-yl-3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]propanoic acid Chemical compound C1=CC=CC2=CC([C@@H](NC(=O)CCCCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CN=C21 DSVRSYVZAMHQET-QFIPXVFZSA-N 0.000 claims description 6
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 6
- 229940122156 Cathepsin K inhibitor Drugs 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 239000002834 estrogen receptor modulator Substances 0.000 claims description 6
- 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 6
- YICWVYSPJDTUBI-LJQANCHMSA-N (2r)-2-pyrimidin-5-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1([C@@H](CCCCCCCC=2N=C3NCCCC3=CC=2)C(=O)O)=CN=CN=C1 YICWVYSPJDTUBI-LJQANCHMSA-N 0.000 claims description 5
- IBRHOSNJPHFAIP-UHFFFAOYSA-N 3-quinolin-3-yl-7-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-ylmethylamino)heptanoic acid Chemical compound C1=CC=CC2=CC(C(CCCCNCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CN=C21 IBRHOSNJPHFAIP-UHFFFAOYSA-N 0.000 claims description 5
- 208000027418 Wounds and injury Diseases 0.000 claims description 5
- 125000004691 alkyl thio carbonyl group Chemical group 0.000 claims description 5
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 5
- 230000001028 anti-proliverative effect Effects 0.000 claims description 5
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 5
- 231100000433 cytotoxic Toxicity 0.000 claims description 5
- 230000001472 cytotoxic effect Effects 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 5
- BECORCOXZFLCKV-LJQANCHMSA-N (2R)-2-(6-aminopyridin-3-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound Nc1ccc(cn1)[C@@H](CCCCCCCc1ccc2CCCNc2n1)C(O)=O BECORCOXZFLCKV-LJQANCHMSA-N 0.000 claims description 4
- ANCHZQJTSKHDFM-HXUWFJFHSA-N (2S)-2-(2,3-dihydro-1-benzofuran-6-yl)-3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]propanoic acid Chemical compound OC(=O)[C@H](CNC(=O)CCCCc1ccc2CCCNc2n1)c1ccc2CCOc2c1 ANCHZQJTSKHDFM-HXUWFJFHSA-N 0.000 claims description 4
- YUGIIBOBDNRWTQ-QFIPXVFZSA-N (2S)-2-(2,3-dihydro-1-benzofuran-6-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@@H](CCCCCCCc1ccc2CCCNc2n1)c1ccc2CCOc2c1 YUGIIBOBDNRWTQ-QFIPXVFZSA-N 0.000 claims description 4
- YHEYEOGCIDCGAJ-HSZRJFAPSA-N (2r)-2-quinolin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=CC2=CC([C@@H](CCCCCCCC=3N=C4NCCCC4=CC=3)C(=O)O)=CN=C21 YHEYEOGCIDCGAJ-HSZRJFAPSA-N 0.000 claims description 4
- BZNJQSLXUULJOU-NRFANRHFSA-N (2s)-2-(benzenesulfonamido)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound N([C@@H](CCCCCCCC=1N=C2NCCCC2=CC=1)C(=O)O)S(=O)(=O)C1=CC=CC=C1 BZNJQSLXUULJOU-NRFANRHFSA-N 0.000 claims description 4
- HXXQXENMUIBGAJ-FQEVSTJZSA-N (2s)-2-pyridin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1([C@H](CCCCCCCC=2N=C3NCCCC3=CC=2)C(=O)O)=CC=CN=C1 HXXQXENMUIBGAJ-FQEVSTJZSA-N 0.000 claims description 4
- CIPHVAAOCRJYHM-SFHVURJKSA-N (3s)-3-(3-fluorophenyl)-3-[3-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)propylcarbamoylamino]propanoic acid Chemical compound C1([C@@H](NC(=O)NCCCC=2N=C3NCCCC3=CC=2)CC(=O)O)=CC=CC(F)=C1 CIPHVAAOCRJYHM-SFHVURJKSA-N 0.000 claims description 4
- ALHZHUMUPQSMPP-SFHVURJKSA-N (3s)-3-[5-(2-aminopyrimidin-4-yl)pentanoylamino]-3-quinolin-3-ylpropanoic acid Chemical compound NC1=NC=CC(CCCCC(=O)N[C@@H](CC(O)=O)C=2C=C3C=CC=CC3=NC=2)=N1 ALHZHUMUPQSMPP-SFHVURJKSA-N 0.000 claims description 4
- 125000006624 (C1-C6) alkoxycarbonylamino group Chemical group 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 4
- ZCZVGQCBSJLDDS-UHFFFAOYSA-N 1,2,3,4-tetrahydro-1,8-naphthyridine Chemical compound C1=CC=C2CCCNC2=N1 ZCZVGQCBSJLDDS-UHFFFAOYSA-N 0.000 claims description 4
- ZYFFFEKOJMRMKW-UHFFFAOYSA-N 2-(benzenesulfonamido)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)non-4-enoic acid Chemical compound C=1C=C2CCCNC2=NC=1CCCCC=CCC(C(=O)O)NS(=O)(=O)C1=CC=CC=C1 ZYFFFEKOJMRMKW-UHFFFAOYSA-N 0.000 claims description 4
- XBHBFRSVZRSVIA-UHFFFAOYSA-N 3-(2,3-dihydro-1-benzofuran-6-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=C2CCOC2=CC(C(CCCCCCC=2N=C3NCCCC3=CC=2)CC(=O)O)=C1 XBHBFRSVZRSVIA-UHFFFAOYSA-N 0.000 claims description 4
- SQIDFFKYMURYAR-UHFFFAOYSA-N 3-(6-methoxypyridin-3-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(OC)=CC=C1C(CC(O)=O)CCCCCCC1=CC=C(CCCN2)C2=N1 SQIDFFKYMURYAR-UHFFFAOYSA-N 0.000 claims description 4
- KZJICBSAPNYGNW-UHFFFAOYSA-N 9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1CCNC2=NC(CCCCCCCCC(=O)O)=CC=C21 KZJICBSAPNYGNW-UHFFFAOYSA-N 0.000 claims description 4
- 229940124226 Farnesyltransferase inhibitor Drugs 0.000 claims description 4
- 229940122091 Geranylgeranyltransferase inhibitor Drugs 0.000 claims description 4
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 claims description 4
- 206010052428 Wound Diseases 0.000 claims description 4
- 125000005197 alkyl carbonyloxy alkyl group Chemical group 0.000 claims description 4
- 125000005154 alkyl sulfonyl amino alkyl group Chemical group 0.000 claims description 4
- 125000002950 monocyclic group Chemical group 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000006574 non-aromatic ring group Chemical group 0.000 claims description 4
- JIOVRWQIZPEDAX-HXUWFJFHSA-N (2R)-2-(6-methoxypyridin-3-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound COc1ccc(cn1)[C@@H](CCCCCCCc1ccc2CCCNc2n1)C(O)=O JIOVRWQIZPEDAX-HXUWFJFHSA-N 0.000 claims description 3
- JDEQVTXOWUTPAS-OAQYLSRUSA-N (2R)-2-furo[2,3-b]pyridin-5-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound O1C=CC=2C1=NC=C(C=2)[C@H](C(=O)O)CCCCCCCC1=NC=2NCCCC=2C=C1 JDEQVTXOWUTPAS-OAQYLSRUSA-N 0.000 claims description 3
- KJHPWLBZAADRMA-OAQYLSRUSA-N (2S)-2-(1-benzothiophen-2-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@H](CCCCCCCc1ccc2CCCNc2n1)c1cc2ccccc2s1 KJHPWLBZAADRMA-OAQYLSRUSA-N 0.000 claims description 3
- JEFVGZNNIIERNY-IBGZPJMESA-N (2S)-2-(2,3-dihydrofuro[3,2-b]pyridin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@@H](CCCCCCCc1ccc2CCCNc2n1)c1ccc2OCCc2n1 JEFVGZNNIIERNY-IBGZPJMESA-N 0.000 claims description 3
- KGWGLIZVXQHKNZ-NRFANRHFSA-N (2S)-2-(3-fluorophenyl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound OC(=O)[C@@H](CCCCCCCc1ccc2CCCNc2n1)c1cccc(F)c1 KGWGLIZVXQHKNZ-NRFANRHFSA-N 0.000 claims description 3
- KJHPWLBZAADRMA-NRFANRHFSA-N (2r)-2-(1-benzothiophen-2-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=C2SC([C@H](CCCCCCCC=3N=C4NCCCC4=CC=3)C(=O)O)=CC2=C1 KJHPWLBZAADRMA-NRFANRHFSA-N 0.000 claims description 3
- FIEWTBHPTPMJPY-NRFANRHFSA-N (2r)-2-quinolin-3-yl-3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]propanoic acid Chemical compound C1=CC=CC2=CC([C@H](CNC(=O)CCCCC=3N=C4NCCCC4=CC=3)C(=O)O)=CN=C21 FIEWTBHPTPMJPY-NRFANRHFSA-N 0.000 claims description 3
- BECORCOXZFLCKV-IBGZPJMESA-N (2s)-2-(6-aminopyridin-3-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(N)=CC=C1[C@@H](C(O)=O)CCCCCCCC1=CC=C(CCCN2)C2=N1 BECORCOXZFLCKV-IBGZPJMESA-N 0.000 claims description 3
- MFTUHLIYZMISCB-QFIPXVFZSA-N (2s)-2-(benzenesulfonamido)-10-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)decanoic acid Chemical compound N([C@@H](CCCCCCCCC=1N=C2NCCCC2=CC=1)C(=O)O)S(=O)(=O)C1=CC=CC=C1 MFTUHLIYZMISCB-QFIPXVFZSA-N 0.000 claims description 3
- LTSYOWOYZKAEHL-IBGZPJMESA-N (2s)-2-(benzenesulfonamido)-3-[5-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)pentanoylamino]propanoic acid Chemical compound N([C@@H](CNC(=O)CCCCC=1N=C2NCCCC2=CC=1)C(=O)O)S(=O)(=O)C1=CC=CC=C1 LTSYOWOYZKAEHL-IBGZPJMESA-N 0.000 claims description 3
- KLWNZLIFUDCWEC-FQEVSTJZSA-N (2s)-2-(benzenesulfonamido)-8-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)octanoic acid Chemical compound N([C@@H](CCCCCCC=1N=C2NCCCC2=CC=1)C(=O)O)S(=O)(=O)C1=CC=CC=C1 KLWNZLIFUDCWEC-FQEVSTJZSA-N 0.000 claims description 3
- WCPGJSACNAWSRU-FTBISJDPSA-N (2s)-2-(cyclohexylmethylsulfonylamino)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid;hydrochloride Chemical compound Cl.N([C@@H](CCCCCCCC=1N=C2NCCCC2=CC=1)C(=O)O)S(=O)(=O)CC1CCCCC1 WCPGJSACNAWSRU-FTBISJDPSA-N 0.000 claims description 3
- HXBWKHOYFZZPIE-VITLOXRHSA-N (2s)-2-[[(4s)-7,7-dimethyl-3-oxo-4-bicyclo[2.2.1]heptanyl]methylsulfonylamino]-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid;hydrochloride Chemical compound Cl.C1CCNC2=NC(CCCCCCC[C@H](NS(=O)(=O)C[C@@]34CCC(CC4=O)C3(C)C)C(O)=O)=CC=C21 HXBWKHOYFZZPIE-VITLOXRHSA-N 0.000 claims description 3
- YHEYEOGCIDCGAJ-QHCPKHFHSA-N (2s)-2-quinolin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=CC2=CC([C@H](CCCCCCCC=3N=C4NCCCC4=CC=3)C(=O)O)=CN=C21 YHEYEOGCIDCGAJ-QHCPKHFHSA-N 0.000 claims description 3
- ZZIXZGZHBBXCPU-UHFFFAOYSA-N 3-(1-benzothiophen-2-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=C2SC(C(CCCCCCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CC2=C1 ZZIXZGZHBBXCPU-UHFFFAOYSA-N 0.000 claims description 3
- ASZOUZVUOPXKBN-UHFFFAOYSA-N 3-(2,3-dihydrofuro[3,2-b]pyridin-5-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=C2OCCC2=NC(C(CCCCCCC=2N=C3NCCCC3=CC=2)CC(=O)O)=C1 ASZOUZVUOPXKBN-UHFFFAOYSA-N 0.000 claims description 3
- UKHMZQUOAFMAEY-UHFFFAOYSA-N 3-(6-aminopyridin-3-yl)-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=NC(N)=CC=C1C(CC(O)=O)CCCCCCC1=CC=C(CCCN2)C2=N1 UKHMZQUOAFMAEY-UHFFFAOYSA-N 0.000 claims description 3
- UVCMFCSWFKXNDZ-UHFFFAOYSA-N 6-oxo-3-quinolin-3-yl-9-(5,6,7,8-tetrahydro-1,8-naphthyridin-2-yl)nonanoic acid Chemical compound C1=CC=CC2=CC(C(CCC(=O)CCCC=3N=C4NCCCC4=CC=3)CC(=O)O)=CN=C21 UVCMFCSWFKXNDZ-UHFFFAOYSA-N 0.000 claims description 3
- MFQYADPOLMPVJP-UHFFFAOYSA-N 7-[acetyl(5,6,7,8-tetrahydro-1,8-naphthyridin-2-ylmethyl)amino]-3-quinolin-3-ylheptanoic acid Chemical compound C1CCNC2=NC(CN(CCCCC(CC(O)=O)C=3C=C4C=CC=CC4=NC=3)C(=O)C)=CC=C21 MFQYADPOLMPVJP-UHFFFAOYSA-N 0.000 claims description 3
- WLLGDCBGYWAWAY-UHFFFAOYSA-N 7-[methylsulfonyl(5,6,7,8-tetrahydro-1,8-naphthyridin-2-ylmethyl)amino]-3-quinolin-3-ylheptanoic acid Chemical compound C1CCNC2=NC(CN(CCCCC(CC(O)=O)C=3C=C4C=CC=CC4=NC=3)S(=O)(=O)C)=CC=C21 WLLGDCBGYWAWAY-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
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- C07D213/63—One oxygen atom
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- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/08—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having 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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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three 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
- C07D237/14—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/30—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D263/32—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole 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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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole 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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- 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
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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
- C07D401/14—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 three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- 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
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- 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
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- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
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- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US6989997P | 1997-12-17 | 1997-12-17 | |
| GBGB9807382.8A GB9807382D0 (en) | 1998-04-06 | 1998-04-06 | Vitronectin receptor antagonists |
| US8320998P | 1998-04-27 | 1998-04-27 | |
| GBGB9811295.6A GB9811295D0 (en) | 1998-05-26 | 1998-05-26 | Vitronectin receptor antagonists |
| US9262298P | 1998-07-13 | 1998-07-13 | |
| PCT/US1998/026484 WO1999031061A1 (fr) | 1997-12-17 | 1998-12-14 | Antagonistes du recepteur de l'integrine |
Publications (1)
| Publication Number | Publication Date |
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| SK9192000A3 true SK9192000A3 (en) | 2001-03-12 |
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| Application Number | Title | Priority Date | Filing Date |
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| SK919-2000A SK9192000A3 (en) | 1997-12-17 | 1998-12-14 | Integrin receptor antagonists |
Country Status (25)
| Country | Link |
|---|---|
| EP (1) | EP1040098B1 (fr) |
| JP (1) | JP3585839B2 (fr) |
| KR (1) | KR20010033248A (fr) |
| CN (1) | CN1284944A (fr) |
| AT (1) | ATE294163T1 (fr) |
| AU (1) | AU739811B2 (fr) |
| BG (1) | BG104605A (fr) |
| BR (1) | BR9813769A (fr) |
| CA (1) | CA2315220C (fr) |
| DE (1) | DE69829996T2 (fr) |
| EA (1) | EA002822B1 (fr) |
| EE (1) | EE200000362A (fr) |
| ES (1) | ES2241192T3 (fr) |
| GE (1) | GEP20032921B (fr) |
| HR (1) | HRP20000401A2 (fr) |
| HU (1) | HUP0100397A3 (fr) |
| ID (1) | ID24955A (fr) |
| IL (1) | IL136495A0 (fr) |
| IS (1) | IS5521A (fr) |
| NO (1) | NO20003114L (fr) |
| NZ (1) | NZ504893A (fr) |
| PL (1) | PL341215A1 (fr) |
| SK (1) | SK9192000A3 (fr) |
| TR (1) | TR200002557T2 (fr) |
| WO (1) | WO1999031061A1 (fr) |
Families Citing this family (65)
| Publication number | Priority date | Publication date | Assignee | Title |
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| GB9805655D0 (en) | 1998-03-16 | 1998-05-13 | Celltech Therapeutics Ltd | Chemical compounds |
| US6521626B1 (en) | 1998-03-24 | 2003-02-18 | Celltech R&D Limited | Thiocarboxamide derivatives |
| BR9909625A (pt) * | 1998-04-16 | 2002-01-15 | Texas Biotechnology Corp | Amidas n,n-di-substituìdas que inibem a ligação de integrinas a seus receptores |
| GB9814414D0 (en) | 1998-07-03 | 1998-09-02 | Celltech Therapeutics Ltd | Chemical compounds |
| JP2002522540A (ja) * | 1998-08-13 | 2002-07-23 | メルク エンド カムパニー インコーポレーテッド | インテグリン受容体拮抗薬 |
| GB9821061D0 (en) | 1998-09-28 | 1998-11-18 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9826174D0 (en) | 1998-11-30 | 1999-01-20 | Celltech Therapeutics Ltd | Chemical compounds |
| US6518283B1 (en) | 1999-05-28 | 2003-02-11 | Celltech R&D Limited | Squaric acid derivatives |
| CZ20014308A3 (cs) * | 1999-06-02 | 2002-03-13 | Merck And Co., Inc. | Deriváty kyseliny nonanové |
| US6534513B1 (en) | 1999-09-29 | 2003-03-18 | Celltech R&D Limited | Phenylalkanoic acid derivatives |
| CA2386030A1 (fr) * | 1999-10-04 | 2001-04-12 | Merck & Co., Inc. | Antagonistes des recepteurs d'integrine |
| CA2386457A1 (fr) * | 1999-10-06 | 2001-04-12 | Basf Aktiengesellschaft | Inhibiteurs de voie de signalisation de l'endotheline et antagonistes de recepteurs de l'integrine pour traitement combine |
| US6407241B1 (en) | 1999-11-08 | 2002-06-18 | Merck & Co., Inc. | Process and intermediates for the preparation of imidazolidinone αv integrin antagonists |
| GB2356630A (en) | 1999-11-10 | 2001-05-30 | Merck & Co Inc | Intermediates used in the preparation of tetrahydronaphthyridine |
| ATE258177T1 (de) | 1999-11-23 | 2004-02-15 | Merck & Co Inc | Verfahren für die herstellung und zwischenprodukte von tetrahydro-(1,8)- naphthyridin |
| US6455539B2 (en) | 1999-12-23 | 2002-09-24 | Celltech R&D Limited | Squaric acid derivates |
| JP2003520271A (ja) * | 2000-01-24 | 2003-07-02 | メルク エンド カムパニー インコーポレーテッド | αvインテグリン受容体拮抗薬 |
| DE60130910T2 (de) | 2000-04-17 | 2008-07-10 | Ucb Pharma, S.A. | Enamin-derivate als zell-adhäsionsmoleküle |
| US6403608B1 (en) | 2000-05-30 | 2002-06-11 | Celltech R&D, Ltd. | 3-Substituted isoquinolin-1-yl derivatives |
| US6545013B2 (en) | 2000-05-30 | 2003-04-08 | Celltech R&D Limited | 2,7-naphthyridine derivatives |
| US6740654B2 (en) | 2000-07-07 | 2004-05-25 | Celltech R & D Limited | Squaric acid derivatives |
| AU2001275724A1 (en) | 2000-08-02 | 2002-02-13 | Celltech R&D Limited | 3-substituted isoquinolin-1-yl derivatives |
| AU2001290772A1 (en) * | 2000-09-14 | 2002-03-26 | Merck And Co., Inc. | Alpha v integrin receptor antagonists |
| US6444680B1 (en) | 2000-11-30 | 2002-09-03 | Merck & Co., Inc. | Amine salts of an integrin receptor antagonist |
| US6764842B2 (en) | 2001-03-28 | 2004-07-20 | Merck & Co., Inc. | Enantioselective bioreduction for the preparation of integrin receptor antagonist intermediates |
| RU2316337C2 (ru) | 2001-04-24 | 2008-02-10 | Мерк Патент Гмбх | КОМБИНИРОВАННАЯ ТЕРАПИЯ, ИСПОЛЬЗУЮЩАЯ АНТИАНГИОГЕННЫЕ СРЕДСТВА И TNF-α |
| PE20030120A1 (es) * | 2001-06-19 | 2003-02-12 | Merck & Co Inc | Sal amina de un antagonista de receptor de integrin |
| US20040224986A1 (en) | 2002-08-16 | 2004-11-11 | Bart De Corte | Piperidinyl targeting compounds that selectively bind integrins |
| GB0420424D0 (en) * | 2004-09-14 | 2004-10-20 | Ionix Pharmaceuticals Ltd | Therapeutic compounds |
| CA2637387A1 (fr) | 2006-01-18 | 2007-07-26 | Simon Goodman | Traitement specifique utilisant des ligands de l'integrine destine a traiter un cancer |
| EP2101805B1 (fr) | 2007-01-18 | 2012-11-07 | Merck Patent GmbH | Ligands d'intégrine pour utilisation en traitement du cancer |
| CN102026671B (zh) | 2008-03-14 | 2014-09-03 | Visen医药公司 | 整联蛋白靶向试剂及使用其的体内和体外成像方法 |
| WO2010136168A2 (fr) | 2009-05-25 | 2010-12-02 | Merck Patent Gmbh | Administration continue de ligands d'intégrines pour le traitement du cancer |
| WO2011068211A1 (fr) * | 2009-12-04 | 2011-06-09 | 大正製薬株式会社 | Composés 2-pyridones |
| HUE035357T2 (en) * | 2013-02-07 | 2018-05-02 | Scifluor Life Sciences Inc | Fluorinated integrin antagonists |
| US8901144B2 (en) | 2013-02-07 | 2014-12-02 | Scifluor Life Sciences, Llc | Fluorinated 3-(2-oxo-3-(3-arylpropyl)imidazolidin-1-yl)-3-arylpropanoic acid derivatives |
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-
1998
- 1998-12-14 EP EP98963136A patent/EP1040098B1/fr not_active Expired - Lifetime
- 1998-12-14 ES ES98963136T patent/ES2241192T3/es not_active Expired - Lifetime
- 1998-12-14 JP JP2000538988A patent/JP3585839B2/ja not_active Expired - Fee Related
- 1998-12-14 PL PL98341215A patent/PL341215A1/xx unknown
- 1998-12-14 KR KR1020007006677A patent/KR20010033248A/ko not_active Ceased
- 1998-12-14 NZ NZ504893A patent/NZ504893A/xx unknown
- 1998-12-14 AU AU18220/99A patent/AU739811B2/en not_active Ceased
- 1998-12-14 SK SK919-2000A patent/SK9192000A3/sk unknown
- 1998-12-14 WO PCT/US1998/026484 patent/WO1999031061A1/fr not_active Ceased
- 1998-12-14 CA CA002315220A patent/CA2315220C/fr not_active Expired - Fee Related
- 1998-12-14 HU HU0100397A patent/HUP0100397A3/hu unknown
- 1998-12-14 HR HR20000401A patent/HRP20000401A2/hr not_active Application Discontinuation
- 1998-12-14 IL IL13649598A patent/IL136495A0/xx unknown
- 1998-12-14 BR BR9813769-7A patent/BR9813769A/pt not_active IP Right Cessation
- 1998-12-14 AT AT98963136T patent/ATE294163T1/de not_active IP Right Cessation
- 1998-12-14 CN CN98813567A patent/CN1284944A/zh active Pending
- 1998-12-14 GE GEAP19985463A patent/GEP20032921B/en unknown
- 1998-12-14 DE DE69829996T patent/DE69829996T2/de not_active Expired - Fee Related
- 1998-12-14 EA EA200000660A patent/EA002822B1/ru not_active IP Right Cessation
- 1998-12-14 ID IDW20001164A patent/ID24955A/id unknown
- 1998-12-14 EE EEP200000362A patent/EE200000362A/xx unknown
- 1998-12-14 TR TR2000/02557T patent/TR200002557T2/xx unknown
-
2000
- 2000-05-31 IS IS5521A patent/IS5521A/is unknown
- 2000-06-16 NO NO20003114A patent/NO20003114L/no unknown
- 2000-07-13 BG BG104605A patent/BG104605A/bg unknown
Also Published As
| Publication number | Publication date |
|---|---|
| ES2241192T3 (es) | 2005-10-16 |
| IL136495A0 (en) | 2001-06-14 |
| TR200002557T2 (tr) | 2000-12-21 |
| NO20003114L (no) | 2000-08-16 |
| CA2315220A1 (fr) | 1999-06-24 |
| HUP0100397A3 (en) | 2002-10-28 |
| NO20003114D0 (no) | 2000-06-16 |
| HRP20000401A2 (en) | 2001-12-31 |
| GEP20032921B (en) | 2003-03-25 |
| JP3585839B2 (ja) | 2004-11-04 |
| AU1822099A (en) | 1999-07-05 |
| WO1999031061A1 (fr) | 1999-06-24 |
| EP1040098A1 (fr) | 2000-10-04 |
| JP2002508355A (ja) | 2002-03-19 |
| EP1040098B1 (fr) | 2005-04-27 |
| EA200000660A1 (ru) | 2001-02-26 |
| EE200000362A (et) | 2001-12-17 |
| BG104605A (bg) | 2001-05-31 |
| DE69829996D1 (de) | 2005-06-02 |
| EA002822B1 (ru) | 2002-10-31 |
| CA2315220C (fr) | 2006-03-21 |
| ID24955A (id) | 2000-08-31 |
| EP1040098A4 (fr) | 2002-10-30 |
| ATE294163T1 (de) | 2005-05-15 |
| KR20010033248A (ko) | 2001-04-25 |
| BR9813769A (pt) | 2000-10-10 |
| IS5521A (is) | 2000-05-31 |
| PL341215A1 (en) | 2001-03-26 |
| DE69829996T2 (de) | 2006-02-23 |
| HUP0100397A2 (hu) | 2001-09-28 |
| NZ504893A (en) | 2002-10-25 |
| AU739811B2 (en) | 2001-10-18 |
| CN1284944A (zh) | 2001-02-21 |
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