SI20017A - Dušik vsebujoči heteroaromati kot inhibitorji faktorja Xa - Google Patents
Dušik vsebujoči heteroaromati kot inhibitorji faktorja Xa Download PDFInfo
- Publication number
- SI20017A SI20017A SI9720082A SI9720082A SI20017A SI 20017 A SI20017 A SI 20017A SI 9720082 A SI9720082 A SI 9720082A SI 9720082 A SI9720082 A SI 9720082A SI 20017 A SI20017 A SI 20017A
- Authority
- SI
- Slovenia
- Prior art keywords
- aminocarbonyl
- pyrazole
- biphen
- phenyl
- methyl
- Prior art date
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- 229910052757 nitrogen Inorganic materials 0.000 title claims abstract description 59
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 title description 29
- 229940123583 Factor Xa inhibitor Drugs 0.000 title description 5
- 150000002390 heteroarenes Chemical class 0.000 title description 4
- -1 nitrogen containing heteroaromatics Chemical class 0.000 claims abstract description 826
- 150000003839 salts Chemical group 0.000 claims abstract description 30
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 551
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 claims description 280
- 150000001875 compounds Chemical class 0.000 claims description 231
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 154
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 108
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Substances C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 92
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 76
- 125000000217 alkyl group Chemical group 0.000 claims description 65
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 58
- 150000003536 tetrazoles Chemical class 0.000 claims description 50
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 48
- 229910052717 sulfur Inorganic materials 0.000 claims description 48
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 46
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 229910052760 oxygen Inorganic materials 0.000 claims description 38
- 229910052801 chlorine Inorganic materials 0.000 claims description 35
- 125000002837 carbocyclic group Chemical group 0.000 claims description 34
- 125000005842 heteroatom Chemical group 0.000 claims description 34
- 229910052731 fluorine Inorganic materials 0.000 claims description 32
- 229920006395 saturated elastomer Polymers 0.000 claims description 32
- 125000004076 pyridyl group Chemical group 0.000 claims description 29
- 229910052739 hydrogen Inorganic materials 0.000 claims description 28
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 26
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 24
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 23
- 229910052799 carbon Inorganic materials 0.000 claims description 22
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 17
- 125000002883 imidazolyl group Chemical group 0.000 claims description 17
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 16
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 15
- 125000004193 piperazinyl group Chemical group 0.000 claims description 15
- 125000001544 thienyl group Chemical group 0.000 claims description 15
- 125000002541 furyl group Chemical group 0.000 claims description 14
- 125000002971 oxazolyl group Chemical group 0.000 claims description 13
- 125000003386 piperidinyl group Chemical group 0.000 claims description 13
- 125000000335 thiazolyl group Chemical group 0.000 claims description 13
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 12
- 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 12
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 12
- 125000002757 morpholinyl group Chemical group 0.000 claims description 11
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 11
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 10
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims description 10
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 10
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 10
- 125000001399 1,2,3-triazolyl group Chemical group N1N=NC(=C1)* 0.000 claims description 9
- 125000001376 1,2,4-triazolyl group Chemical group N1N=C(N=C1)* 0.000 claims description 9
- 125000004517 1,2,5-thiadiazolyl group Chemical group 0.000 claims description 9
- 125000001781 1,3,4-oxadiazolyl group Chemical group 0.000 claims description 9
- 125000004520 1,3,4-thiadiazolyl group Chemical group 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- 125000004511 1,2,3-thiadiazolyl group Chemical group 0.000 claims description 8
- KOPFEFZSAMLEHK-UHFFFAOYSA-N 1h-pyrazole-5-carboxylic acid Chemical compound OC(=O)C=1C=CNN=1 KOPFEFZSAMLEHK-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 7
- 125000006569 (C5-C6) heterocyclic group Chemical group 0.000 claims description 7
- 125000004514 1,2,4-thiadiazolyl group Chemical group 0.000 claims description 7
- 125000004506 1,2,5-oxadiazolyl group Chemical group 0.000 claims description 7
- LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical group NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 claims description 7
- 125000005196 alkyl carbonyloxy group Chemical group 0.000 claims description 7
- 125000002816 methylsulfanyl group Chemical group [H]C([H])([H])S[*] 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- XKVUYEYANWFIJX-UHFFFAOYSA-N 5-methyl-1h-pyrazole Chemical compound CC1=CC=NN1 XKVUYEYANWFIJX-UHFFFAOYSA-N 0.000 claims description 6
- 125000002947 alkylene group Chemical group 0.000 claims description 6
- 125000003785 benzimidazolyl group Chemical group N1=C(NC2=C1C=CC=C2)* 0.000 claims description 6
- 125000004603 benzisoxazolyl group Chemical group O1N=C(C2=C1C=CC=C2)* 0.000 claims description 6
- 125000004122 cyclic group Chemical group 0.000 claims description 6
- 125000001041 indolyl group Chemical group 0.000 claims description 6
- 125000003971 isoxazolinyl group Chemical group 0.000 claims description 6
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 6
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
- BNYCHCAYYYRJSH-UHFFFAOYSA-N 1h-pyrazole-5-carboxamide Chemical compound NC(=O)C1=CC=NN1 BNYCHCAYYYRJSH-UHFFFAOYSA-N 0.000 claims description 5
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 5
- 125000005161 aryl oxy carbonyl group Chemical group 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 5
- 125000005322 morpholin-1-yl group Chemical group 0.000 claims description 5
- 230000009424 thromboembolic effect Effects 0.000 claims description 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 4
- 125000004916 (C1-C6) alkylcarbonyl group Chemical group 0.000 claims description 4
- 125000004173 1-benzimidazolyl group Chemical group [H]C1=NC2=C([H])C([H])=C([H])C([H])=C2N1* 0.000 claims description 4
- ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 4
- 125000004182 2-chlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 4
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 4
- VLRGXXKFHVJQOL-UHFFFAOYSA-N 3-chloropentane-2,4-dione Chemical compound CC(=O)C(Cl)C(C)=O VLRGXXKFHVJQOL-UHFFFAOYSA-N 0.000 claims description 4
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000005199 aryl carbonyloxy group Chemical group 0.000 claims description 4
- 125000004604 benzisothiazolyl group Chemical group S1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000001164 benzothiazolyl group Chemical group S1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000004541 benzoxazolyl group Chemical group O1C(=NC2=C1C=CC=C2)* 0.000 claims description 4
- 125000003739 carbamimidoyl group Chemical group C(N)(=N)* 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 claims description 4
- 125000005438 isoindazolyl group Chemical group 0.000 claims description 4
- 125000006533 methyl amino methyl group Chemical group [H]N(C([H])([H])[H])C([H])([H])* 0.000 claims description 4
- LYSRTEUWXYZUDB-UHFFFAOYSA-N n-methyl-1-(1h-pyrazol-5-yl)methanesulfonamide Chemical compound CNS(=O)(=O)CC=1C=CNN=1 LYSRTEUWXYZUDB-UHFFFAOYSA-N 0.000 claims description 4
- 125000003261 o-tolyl group Chemical group [H]C1=C([H])C(*)=C(C([H])=C1[H])C([H])([H])[H] 0.000 claims description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims description 4
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000004504 1,2,4-oxadiazolyl group Chemical group 0.000 claims description 3
- XTRBYUHWHOHGKT-UHFFFAOYSA-N 2-(3-carbamimidoylphenyl)-5-methyl-n-(3-phenylpropyl)pyrazole-3-carboxamide Chemical compound C=1C=CC(C(N)=N)=CC=1N1N=C(C)C=C1C(=O)NCCCC1=CC=CC=C1 XTRBYUHWHOHGKT-UHFFFAOYSA-N 0.000 claims description 3
- JOIGRZLCDQUNIN-UHFFFAOYSA-N 2-(3-carbamimidoylphenyl)-5-methyl-n-(4-propan-2-yloxyphenyl)pyrazole-3-carboxamide Chemical compound C1=CC(OC(C)C)=CC=C1NC(=O)C1=CC(C)=NN1C1=CC=CC(C(N)=N)=C1 JOIGRZLCDQUNIN-UHFFFAOYSA-N 0.000 claims description 3
- VJZDWFPLYNSLAI-UHFFFAOYSA-N 2-(3-cyanophenyl)-5-methyl-n-[5-(2-methylsulfonylphenyl)pyrimidin-2-yl]pyrazole-3-carboxamide Chemical compound C=1C=CC(C#N)=CC=1N1N=C(C)C=C1C(=O)NC(N=C1)=NC=C1C1=CC=CC=C1S(C)(=O)=O VJZDWFPLYNSLAI-UHFFFAOYSA-N 0.000 claims description 3
- IMBBXSASDSZJSX-UHFFFAOYSA-N 4-Carboxypyrazole Chemical compound OC(=O)C=1C=NNC=1 IMBBXSASDSZJSX-UHFFFAOYSA-N 0.000 claims description 3
- PYXNITNKYBLBMW-UHFFFAOYSA-N 5-(trifluoromethyl)-1h-pyrazole Chemical compound FC(F)(F)C1=CC=NN1 PYXNITNKYBLBMW-UHFFFAOYSA-N 0.000 claims description 3
- 150000003937 benzamidines Chemical class 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
- 229960001760 dimethyl sulfoxide Drugs 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 3
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 3
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 3
- 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 2
- LZADISKPQALSQY-UHFFFAOYSA-N 2-(3-carbamimidoylphenyl)-5-methyl-N-[4-(trifluoromethyl)phenyl]pyrazole-3-carboxamide Chemical compound C=1C=CC(C(N)=N)=CC=1N1N=C(C)C=C1C(=O)NC1=CC=C(C(F)(F)F)C=C1 LZADISKPQALSQY-UHFFFAOYSA-N 0.000 claims description 2
- 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 2
- UMAOEOPCSCXTLY-UHFFFAOYSA-N 5-(methylsulfonylmethyl)-1h-pyrazole Chemical compound CS(=O)(=O)CC1=CC=NN1 UMAOEOPCSCXTLY-UHFFFAOYSA-N 0.000 claims description 2
- JDRGMCYOFFMFLW-UHFFFAOYSA-N 5-methylsulfinyl-1h-pyrazole Chemical compound CS(=O)C=1C=CNN=1 JDRGMCYOFFMFLW-UHFFFAOYSA-N 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 230000002265 prevention Effects 0.000 claims description 2
- 125000006413 ring segment Chemical group 0.000 claims description 2
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims 2
- NNLOFVIBAZFDRB-UHFFFAOYSA-N 2-(3-carbamimidoylphenyl)-5-methyl-n-[5-(2-methylsulfonylphenyl)pyrimidin-2-yl]pyrazole-3-carboxamide Chemical compound C=1C=CC(C(N)=N)=CC=1N1N=C(C)C=C1C(=O)NC(N=C1)=NC=C1C1=CC=CC=C1S(C)(=O)=O NNLOFVIBAZFDRB-UHFFFAOYSA-N 0.000 claims 1
- ZPAJAVGZZKPCTN-UHFFFAOYSA-N 5-methyl-1h-pyrazole-4-carboxamide Chemical compound CC1=NNC=C1C(N)=O ZPAJAVGZZKPCTN-UHFFFAOYSA-N 0.000 claims 1
- DBTDEFJAFBUGPP-UHFFFAOYSA-N Methanethial Chemical compound S=C DBTDEFJAFBUGPP-UHFFFAOYSA-N 0.000 claims 1
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 1
- 125000002962 imidazol-1-yl group Chemical group [*]N1C([H])=NC([H])=C1[H] 0.000 claims 1
- MYWUZJCMWCOHBA-VIFPVBQESA-N methamphetamine Chemical class CN[C@@H](C)CC1=CC=CC=C1 MYWUZJCMWCOHBA-VIFPVBQESA-N 0.000 claims 1
- 125000006261 methyl amino sulfonyl group Chemical group [H]N(C([H])([H])[H])S(*)(=O)=O 0.000 claims 1
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims 1
- 239000000651 prodrug Chemical group 0.000 abstract description 14
- 229940002612 prodrug Drugs 0.000 abstract description 14
- 108010074860 Factor Xa Proteins 0.000 abstract description 7
- 239000003112 inhibitor Substances 0.000 abstract description 4
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- 238000002360 preparation method Methods 0.000 description 124
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- 235000019439 ethyl acetate Nutrition 0.000 description 114
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 102
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- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 78
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- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
- 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 description 1
- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- 125000004621 quinuclidinyl group Chemical group N12C(CC(CC1)CC2)* 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 239000012047 saturated solution Substances 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- JPJALAQPGMAKDF-UHFFFAOYSA-N selenium dioxide Chemical compound O=[Se]=O JPJALAQPGMAKDF-UHFFFAOYSA-N 0.000 description 1
- 239000003521 serotonin 5-HT1 receptor agonist Substances 0.000 description 1
- 229910001961 silver nitrate Inorganic materials 0.000 description 1
- XGVXKJKTISMIOW-ZDUSSCGKSA-N simurosertib Chemical compound N1N=CC(C=2SC=3C(=O)NC(=NC=3C=2)[C@H]2N3CCC(CC3)C2)=C1C XGVXKJKTISMIOW-ZDUSSCGKSA-N 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 235000010288 sodium nitrite Nutrition 0.000 description 1
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical class [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 1
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 description 1
- OVYTZAASVAZITK-UHFFFAOYSA-M sodium;ethanol;hydroxide Chemical compound [OH-].[Na+].CCO OVYTZAASVAZITK-UHFFFAOYSA-M 0.000 description 1
- 239000008279 sol Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 150000003413 spiro compounds Chemical class 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Inorganic materials O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 229940042055 systemic antimycotics triazole derivative Drugs 0.000 description 1
- FTYCOVOIQULCRH-UHFFFAOYSA-N tert-butyl 2-amino-5-(2-methylsulfonylphenyl)pyridine-3-carboxylate Chemical compound C(C)(C)(C)OC(=O)C=1C(=NC=C(C=1)C1=C(C=CC=C1)S(=O)(=O)C)N FTYCOVOIQULCRH-UHFFFAOYSA-N 0.000 description 1
- PCGBBORWJGYBGC-UHFFFAOYSA-N tert-butyl 3-amino-5-bromopyridine-2-carboxylate Chemical compound CC(C)(C)OC(=O)C1=NC=C(Br)C=C1N PCGBBORWJGYBGC-UHFFFAOYSA-N 0.000 description 1
- UEOGBYVGMCQSIN-UHFFFAOYSA-N tert-butyl N-[(2-methylpropan-2-yl)oxycarbonyl]-N-[5-(2-methylsulfonylphenyl)pyridin-2-yl]carbamate Chemical compound C(C)(C)(C)OC(=O)N(C(=O)OC(C)(C)C)C1=NC=C(C=C1)C1=C(C=CC=C1)S(=O)(=O)C UEOGBYVGMCQSIN-UHFFFAOYSA-N 0.000 description 1
- DMHILFAMOKMHSO-UHFFFAOYSA-N tert-butyl n-(4-bromo-2-fluorophenyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1=CC=C(Br)C=C1F DMHILFAMOKMHSO-UHFFFAOYSA-N 0.000 description 1
- DIWWZVFHGNWBBT-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonyl]-n-[5-(2-methylsulfanylphenyl)pyridin-2-yl]carbamate Chemical compound CSC1=CC=CC=C1C1=CC=C(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)N=C1 DIWWZVFHGNWBBT-UHFFFAOYSA-N 0.000 description 1
- WRRWQJHGYFNSNN-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonyl]-n-[5-(2-methylsulfonylphenyl)pyrimidin-2-yl]carbamate Chemical compound C1=NC(N(C(=O)OC(C)(C)C)C(=O)OC(C)(C)C)=NC=C1C1=CC=CC=C1S(C)(=O)=O WRRWQJHGYFNSNN-UHFFFAOYSA-N 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000003039 tetrahydroisoquinolinyl group Chemical group C1(NCCC2=CC=CC=C12)* 0.000 description 1
- 125000000147 tetrahydroquinolinyl group Chemical group N1(CCCC2=CC=CC=C12)* 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 125000004001 thioalkyl group Chemical group 0.000 description 1
- DHCDFWKWKRSZHF-UHFFFAOYSA-L thiosulfate(2-) Chemical compound [O-]S([S-])(=O)=O DHCDFWKWKRSZHF-UHFFFAOYSA-L 0.000 description 1
- 210000001519 tissue Anatomy 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 238000001890 transfection Methods 0.000 description 1
- 125000005270 trialkylamine group Chemical group 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- 230000001960 triggered effect Effects 0.000 description 1
- NHDIQVFFNDKAQU-UHFFFAOYSA-N tripropan-2-yl borate Chemical compound CC(C)OB(OC(C)C)OC(C)C NHDIQVFFNDKAQU-UHFFFAOYSA-N 0.000 description 1
- 239000012588 trypsin Substances 0.000 description 1
- 230000001810 trypsinlike Effects 0.000 description 1
- PXXNTAGJWPJAGM-UHFFFAOYSA-N vertaline Natural products C1C2C=3C=C(OC)C(OC)=CC=3OC(C=C3)=CC=C3CCC(=O)OC1CC1N2CCCC1 PXXNTAGJWPJAGM-UHFFFAOYSA-N 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 238000010792 warming Methods 0.000 description 1
- 125000001834 xanthenyl group Chemical group C1=CC=CC=2OC3=CC=CC=C3C(C12)* 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
- 239000011592 zinc chloride Substances 0.000 description 1
- 235000005074 zinc chloride Nutrition 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D257/00—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms
- C07D257/02—Heterocyclic compounds containing rings having four nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D257/04—Five-membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—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
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—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
- C07D231/14—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 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—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
- C07D231/14—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 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
- C07D231/16—Halogen atoms or nitro radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—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
- C07D231/14—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 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
- C07D231/18—One oxygen or sulfur atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—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
- C07D231/14—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 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
- C07D231/38—Nitrogen atoms
- C07D231/40—Acylated on said nitrogen atom
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—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
- C07D231/14—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 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
- C07D231/38—Nitrogen atoms
- C07D231/42—Benzene-sulfonamido pyrazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- 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
- C07D233/66—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 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
- C07D233/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/04—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles
- C07D249/06—1,2,3-Triazoles; Hydrogenated 1,2,3-triazoles with aryl radicals directly attached to ring atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
- C07D249/10—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles 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
-
- 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
- C07D401/04—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 directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D401/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D403/12—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 chain containing hetero atoms as chain links
-
- 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
- C07D417/02—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 two hetero rings
- C07D417/12—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 two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Hematology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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US76985996A | 1996-12-23 | 1996-12-23 | |
US87994497A | 1997-06-20 | 1997-06-20 | |
PCT/US1997/022895 WO1998028269A1 (en) | 1996-12-23 | 1997-12-15 | NITROGEN CONTAINING HETEROAROMATICS AS FACTOR Xa INHIBITORS |
Publications (1)
Publication Number | Publication Date |
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SI20017A true SI20017A (sl) | 2000-02-29 |
Family
ID=27118232
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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SI9720082A SI20017A (sl) | 1996-12-23 | 1997-12-15 | Dušik vsebujoči heteroaromati kot inhibitorji faktorja Xa |
Country Status (25)
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EP (1) | EP0946508B1 (cs) |
JP (1) | JP2001509145A (cs) |
KR (1) | KR20000062284A (cs) |
CN (1) | CN1246847A (cs) |
AR (1) | AR020305A1 (cs) |
AT (1) | ATE443698T1 (cs) |
AU (1) | AU730224B2 (cs) |
CA (1) | CA2275796A1 (cs) |
CZ (1) | CZ225699A3 (cs) |
DE (1) | DE69739593D1 (cs) |
EA (1) | EA003056B1 (cs) |
EE (1) | EE9900316A (cs) |
ES (1) | ES2331860T3 (cs) |
HR (1) | HRP970698A2 (cs) |
HU (1) | HUP0000735A3 (cs) |
IL (1) | IL130286A0 (cs) |
LV (1) | LV12430B (cs) |
MX (1) | MX9905878A (cs) |
NO (1) | NO313190B1 (cs) |
NZ (1) | NZ336162A (cs) |
PL (1) | PL334250A1 (cs) |
SI (1) | SI20017A (cs) |
SK (1) | SK86699A3 (cs) |
TW (1) | TW492971B (cs) |
WO (1) | WO1998028269A1 (cs) |
Families Citing this family (131)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1998052944A1 (en) * | 1997-05-19 | 1998-11-26 | Sugen, Inc. | Heteroarylcarboxamide compounds active against protein tyrosine kinase related disorders |
AU7976998A (en) * | 1997-06-19 | 1999-01-04 | Du Pont Merck Pharmaceutical Company, The | (amidino)6-membered aromatics as factor xa inhibitors |
US6271237B1 (en) | 1997-12-22 | 2001-08-07 | Dupont Pharmaceuticals Company | Nitrogen containing heteromatics with ortho-substituted P1s as factor Xa inhabitors |
AU1724499A (en) * | 1997-12-22 | 1999-07-12 | Du Pont Pharmaceuticals Company | Nitrogen containing heteroaromatics with ortho-substituted p1's as factor xa inhibitors |
US6900228B1 (en) | 1998-03-10 | 2005-05-31 | Research Triangle Institute | Opiate compounds, methods of making and methods of use |
ES2230841T3 (es) * | 1998-03-27 | 2005-05-01 | Bristol-Myers Squibb Pharma Company | Pirazolinas y triazolinas disustituidas como inhibidores del factor xa. |
CA2348740A1 (en) * | 1998-12-23 | 2000-07-06 | Ruth R. Wexler | Thrombin or factor xa inhibitors |
JP2003522733A (ja) | 1999-02-11 | 2003-07-29 | コア セラピューティクス,インコーポレイティド | Xa因子の阻害剤としてのアルケニルおよびアルキニル化合物 |
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- 1997-12-15 EE EEP199900316A patent/EE9900316A/xx unknown
- 1997-12-15 AU AU56020/98A patent/AU730224B2/en not_active Ceased
- 1997-12-15 DE DE69739593T patent/DE69739593D1/de not_active Expired - Lifetime
- 1997-12-15 CA CA002275796A patent/CA2275796A1/en not_active Abandoned
- 1997-12-22 HR HR08/879,944A patent/HRP970698A2/hr not_active Application Discontinuation
- 1997-12-23 AR ARP970106177A patent/AR020305A1/es not_active Application Discontinuation
-
1998
- 1998-02-03 TW TW086119637A patent/TW492971B/zh not_active IP Right Cessation
-
1999
- 1999-06-01 NO NO19992633A patent/NO313190B1/no unknown
- 1999-06-22 MX MX9905878A patent/MX9905878A/es not_active Application Discontinuation
- 1999-07-30 LV LVP-99-99A patent/LV12430B/en unknown
Also Published As
Publication number | Publication date |
---|---|
NZ336162A (en) | 2000-09-29 |
SK86699A3 (en) | 2000-11-07 |
NO992633L (no) | 1999-08-20 |
PL334250A1 (en) | 2000-02-14 |
EA003056B1 (ru) | 2002-12-26 |
IL130286A0 (en) | 2000-06-01 |
CN1246847A (zh) | 2000-03-08 |
DE69739593D1 (de) | 2009-11-05 |
HUP0000735A3 (en) | 2002-03-28 |
HUP0000735A2 (hu) | 2001-04-28 |
CZ225699A3 (cs) | 2000-09-13 |
ES2331860T3 (es) | 2010-01-18 |
JP2001509145A (ja) | 2001-07-10 |
WO1998028269A1 (en) | 1998-07-02 |
EP0946508B1 (en) | 2009-09-23 |
HRP970698A2 (en) | 1998-10-31 |
AU730224B2 (en) | 2001-03-01 |
CA2275796A1 (en) | 1998-07-02 |
NO992633D0 (no) | 1999-06-01 |
LV12430B (en) | 2000-07-20 |
LV12430A (lv) | 2000-02-20 |
ATE443698T1 (de) | 2009-10-15 |
AU5602098A (en) | 1998-07-17 |
NO313190B1 (no) | 2002-08-26 |
EE9900316A (et) | 2000-02-15 |
MX9905878A (en) | 2000-01-01 |
EP0946508A1 (en) | 1999-10-06 |
KR20000062284A (ko) | 2000-10-25 |
AR020305A1 (es) | 2002-05-08 |
TW492971B (en) | 2002-07-01 |
EA199900591A1 (ru) | 2000-08-28 |
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