HRP20000217A2 - Isoquinolines as urokinase inhibitors - Google Patents
Isoquinolines as urokinase inhibitors Download PDFInfo
- Publication number
- HRP20000217A2 HRP20000217A2 HR20000217A HRP20000217A HRP20000217A2 HR P20000217 A2 HRP20000217 A2 HR P20000217A2 HR 20000217 A HR20000217 A HR 20000217A HR P20000217 A HRP20000217 A HR P20000217A HR P20000217 A2 HRP20000217 A2 HR P20000217A2
- Authority
- HR
- Croatia
- Prior art keywords
- alkylene
- optionally substituted
- compound
- halogens
- group
- Prior art date
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- 239000002797 plasminogen activator inhibitor Substances 0.000 title description 9
- 150000002537 isoquinolines Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 172
- 229910052736 halogen Inorganic materials 0.000 claims description 111
- 238000002360 preparation method Methods 0.000 claims description 100
- 239000000203 mixture Substances 0.000 claims description 83
- 125000005843 halogen group Chemical group 0.000 claims description 66
- 150000003839 salts Chemical class 0.000 claims description 60
- 238000000034 method Methods 0.000 claims description 56
- -1 dioxolyl Chemical group 0.000 claims description 54
- 150000002367 halogens Chemical class 0.000 claims description 48
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 44
- 125000001424 substituent group Chemical group 0.000 claims description 42
- 125000003118 aryl group Chemical group 0.000 claims description 30
- 229910052739 hydrogen Inorganic materials 0.000 claims description 30
- 229910052794 bromium Inorganic materials 0.000 claims description 27
- 125000000217 alkyl group Chemical group 0.000 claims description 26
- 229910052760 oxygen Inorganic materials 0.000 claims description 26
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 23
- 238000006243 chemical reaction Methods 0.000 claims description 21
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 15
- 125000001072 heteroaryl group Chemical group 0.000 claims description 14
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 230000008569 process Effects 0.000 claims description 12
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 11
- 239000003153 chemical reaction reagent Substances 0.000 claims description 11
- OSILBMSORKFRTB-UHFFFAOYSA-N isoquinolin-1-amine Chemical compound C1=CC=C2C(N)=NC=CC2=C1 OSILBMSORKFRTB-UHFFFAOYSA-N 0.000 claims description 11
- 125000004429 atom Chemical group 0.000 claims description 10
- 229920006395 saturated elastomer Polymers 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 8
- 230000033115 angiogenesis Effects 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 230000006378 damage Effects 0.000 claims description 8
- 125000002541 furyl group Chemical group 0.000 claims description 8
- 125000002883 imidazolyl group Chemical group 0.000 claims description 8
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 8
- 125000001624 naphthyl group Chemical group 0.000 claims description 8
- 125000001544 thienyl group Chemical group 0.000 claims description 8
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 claims description 7
- 210000004881 tumor cell Anatomy 0.000 claims description 7
- 230000029663 wound healing Effects 0.000 claims description 7
- 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims description 6
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 6
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 6
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 6
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 6
- 206010040943 Skin Ulcer Diseases 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000005605 benzo group Chemical group 0.000 claims description 6
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 6
- 239000003814 drug Substances 0.000 claims description 6
- 230000002757 inflammatory effect Effects 0.000 claims description 6
- 125000001786 isothiazolyl group Chemical group 0.000 claims description 6
- 125000000842 isoxazolyl group Chemical group 0.000 claims description 6
- 230000001394 metastastic effect Effects 0.000 claims description 6
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 6
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 6
- 125000002971 oxazolyl group Chemical group 0.000 claims description 6
- 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 6
- 125000004309 pyranyl group Chemical group O1C(C=CC=C1)* 0.000 claims description 6
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 6
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 6
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 6
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
- 125000000335 thiazolyl group Chemical group 0.000 claims description 6
- 210000001519 tissue Anatomy 0.000 claims description 6
- 230000007838 tissue remodeling Effects 0.000 claims description 6
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- 206010016654 Fibrosis Diseases 0.000 claims description 5
- 206010064390 Tumour invasion Diseases 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 5
- 210000000988 bone and bone Anatomy 0.000 claims description 5
- 230000009400 cancer invasion Effects 0.000 claims description 5
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 5
- 230000004069 differentiation Effects 0.000 claims description 5
- 230000004761 fibrosis Effects 0.000 claims description 5
- 239000012458 free base Substances 0.000 claims description 5
- 210000002865 immune cell Anatomy 0.000 claims description 5
- 230000008595 infiltration Effects 0.000 claims description 5
- 238000001764 infiltration Methods 0.000 claims description 5
- 238000004519 manufacturing process Methods 0.000 claims description 5
- 230000016087 ovulation Effects 0.000 claims description 5
- 230000021595 spermatogenesis Effects 0.000 claims description 5
- 238000011282 treatment Methods 0.000 claims description 5
- 210000004291 uterus Anatomy 0.000 claims description 5
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-UHFFFAOYSA-N 0.000 claims description 4
- WFWVGNODYCIFAT-UHFFFAOYSA-N 2-(4-chloro-7-phenylsulfanylisoquinolin-1-yl)guanidine Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1SC1=CC=CC=C1 WFWVGNODYCIFAT-UHFFFAOYSA-N 0.000 claims description 4
- NRVVFOKWKSWIIV-UHFFFAOYSA-N 2-(7-sulfamoylisoquinolin-1-yl)guanidine Chemical compound C1=C(S(N)(=O)=O)C=C2C(NC(=N)N)=NC=CC2=C1 NRVVFOKWKSWIIV-UHFFFAOYSA-N 0.000 claims description 4
- RFKKRFPXGHPURP-UHFFFAOYSA-N 2-[7-(benzenesulfonyl)-4-chloroisoquinolin-1-yl]guanidine Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)C1=CC=CC=C1 RFKKRFPXGHPURP-UHFFFAOYSA-N 0.000 claims description 4
- NNEJXIJKGKRBBF-UHFFFAOYSA-N 2-[7-(phenylsulfamoyl)isoquinolin-1-yl]guanidine Chemical compound C1=C2C(NC(=N)N)=NC=CC2=CC=C1S(=O)(=O)NC1=CC=CC=C1 NNEJXIJKGKRBBF-UHFFFAOYSA-N 0.000 claims description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 4
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 4
- 206010029113 Neovascularisation Diseases 0.000 claims description 4
- 125000002947 alkylene group Chemical group 0.000 claims description 4
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 4
- 235000019256 formaldehyde Nutrition 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 4
- 125000004430 oxygen atom Chemical group O* 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
- 125000004434 sulfur atom Chemical group 0.000 claims description 4
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 3
- LZCYTJFZWSPVRX-UHFFFAOYSA-N 2-(4-chloro-7-morpholin-4-ylsulfonylisoquinolin-1-yl)guanidine;hydrochloride Chemical compound Cl.C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)N1CCOCC1 LZCYTJFZWSPVRX-UHFFFAOYSA-N 0.000 claims description 3
- QXVKRCPMWGQPQV-UHFFFAOYSA-N 2-[4-bromo-7-(4-methoxyphenyl)isoquinolin-1-yl]guanidine Chemical compound C1=CC(OC)=CC=C1C1=CC=C(C(Br)=CN=C2NC(N)=N)C2=C1 QXVKRCPMWGQPQV-UHFFFAOYSA-N 0.000 claims description 3
- 150000001409 amidines Chemical class 0.000 claims description 3
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- VYCKDIRCVDCQAE-UHFFFAOYSA-N isoquinolin-3-amine Chemical class C1=CC=C2C=NC(N)=CC2=C1 VYCKDIRCVDCQAE-UHFFFAOYSA-N 0.000 claims description 3
- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 3
- HCACCYBLVLISIO-UHFFFAOYSA-N 2-[4-bromo-7-(3-methoxyphenyl)isoquinolin-1-yl]guanidine Chemical compound COC1=CC=CC(C=2C=C3C(NC(N)=N)=NC=C(Br)C3=CC=2)=C1 HCACCYBLVLISIO-UHFFFAOYSA-N 0.000 claims description 2
- RZXRBCPKMICCFA-UHFFFAOYSA-N 2-[4-chloro-7-(2,6-dimethoxyphenyl)isoquinolin-1-yl]guanidine Chemical compound COC1=CC=CC(OC)=C1C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 RZXRBCPKMICCFA-UHFFFAOYSA-N 0.000 claims description 2
- RJODTPBPYVAHPU-UHFFFAOYSA-N 2-[4-chloro-7-(2-methoxyphenyl)isoquinolin-1-yl]guanidine Chemical compound COC1=CC=CC=C1C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 RJODTPBPYVAHPU-UHFFFAOYSA-N 0.000 claims description 2
- XJVLWXLPNJUSJK-UHFFFAOYSA-N 2-[4-chloro-7-(3-methoxyphenyl)isoquinolin-1-yl]guanidine Chemical compound COC1=CC=CC(C=2C=C3C(NC(N)=N)=NC=C(Cl)C3=CC=2)=C1 XJVLWXLPNJUSJK-UHFFFAOYSA-N 0.000 claims description 2
- MOZIDBOJSUCARX-UHFFFAOYSA-N 2-[4-chloro-7-(4-methoxyphenyl)isoquinolin-1-yl]guanidine Chemical compound C1=CC(OC)=CC=C1C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 MOZIDBOJSUCARX-UHFFFAOYSA-N 0.000 claims description 2
- YQIZHNTYJAUADB-UHFFFAOYSA-N 2-[4-chloro-7-[hydroxy(phenyl)methyl]isoquinolin-1-yl]guanidine Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1C(O)C1=CC=CC=C1 YQIZHNTYJAUADB-UHFFFAOYSA-N 0.000 claims description 2
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 2
- UXNWIRHZMHGOCE-UHFFFAOYSA-N 3-[4-chloro-1-(diaminomethylideneamino)isoquinolin-7-yl]benzoic acid Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1C1=CC=CC(C(O)=O)=C1 UXNWIRHZMHGOCE-UHFFFAOYSA-N 0.000 claims description 2
- 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 claims description 2
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 2
- 125000006519 CCH3 Chemical group 0.000 claims description 2
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 2
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 claims description 2
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
- 125000000649 benzylidene group Chemical group [H]C(=[*])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 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 2
- 125000005879 dioxolanyl group Chemical group 0.000 claims description 2
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
- ZIPLUEXSCPLCEI-UHFFFAOYSA-N iminomethylideneazanide Chemical compound [NH-]C#N ZIPLUEXSCPLCEI-UHFFFAOYSA-N 0.000 claims description 2
- IYRMNDOLPONSCJ-UHFFFAOYSA-N isoquinolin-2-ium;chloride Chemical compound Cl.C1=NC=CC2=CC=CC=C21 IYRMNDOLPONSCJ-UHFFFAOYSA-N 0.000 claims description 2
- 125000005647 linker group Chemical group 0.000 claims description 2
- 125000006237 oxymethylenoxy group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 2
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims description 2
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 2
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical group CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 claims description 2
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 claims description 2
- 230000032692 embryo implantation Effects 0.000 claims 2
- 239000012752 auxiliary agent Substances 0.000 claims 1
- 239000007787 solid Substances 0.000 description 86
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 74
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 74
- 239000000243 solution Substances 0.000 description 65
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 55
- 238000000921 elemental analysis Methods 0.000 description 52
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 41
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 37
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 34
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- 239000002904 solvent Substances 0.000 description 25
- 238000005160 1H NMR spectroscopy Methods 0.000 description 22
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 22
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 22
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 22
- 229910052757 nitrogen Inorganic materials 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
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- 239000003480 eluent Substances 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 18
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- 229910052943 magnesium sulfate Inorganic materials 0.000 description 17
- 235000019341 magnesium sulphate Nutrition 0.000 description 17
- 238000010992 reflux Methods 0.000 description 16
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
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- KWXXBZNOKYQKAI-UHFFFAOYSA-N 7-bromo-1,4-dichloroisoquinoline Chemical compound BrC1=CC=C2C(Cl)=CN=C(Cl)C2=C1 KWXXBZNOKYQKAI-UHFFFAOYSA-N 0.000 description 13
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- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 13
- 239000002253 acid Substances 0.000 description 13
- 239000012267 brine Substances 0.000 description 13
- 229940012957 plasmin Drugs 0.000 description 13
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- 238000004587 chromatography analysis Methods 0.000 description 12
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 12
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
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- 229910002027 silica gel Inorganic materials 0.000 description 11
- 239000000725 suspension Substances 0.000 description 11
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- 229960005356 urokinase Drugs 0.000 description 10
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 9
- 239000002585 base Substances 0.000 description 9
- 238000010511 deprotection reaction Methods 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 8
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 239000006071 cream Substances 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 230000007062 hydrolysis Effects 0.000 description 7
- 238000006460 hydrolysis reaction Methods 0.000 description 7
- 239000002480 mineral oil Substances 0.000 description 7
- 235000010446 mineral oil Nutrition 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 7
- MBXFJGWNDTUZLK-UHFFFAOYSA-N 2-isoquinolin-1-ylguanidine Chemical class C1=CC=C2C(NC(=N)N)=NC=CC2=C1 MBXFJGWNDTUZLK-UHFFFAOYSA-N 0.000 description 6
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
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- PEHDMKYTTRTXSH-UHFFFAOYSA-N n-[6-amino-1-(4-nitroanilino)-1-oxohexan-2-yl]-1-[2-[(4-methylphenyl)sulfonylamino]acetyl]pyrrolidine-2-carboxamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)NCC(=O)N1C(C(=O)NC(CCCCN)C(=O)NC=2C=CC(=CC=2)[N+]([O-])=O)CCC1 PEHDMKYTTRTXSH-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 1
- 230000037311 normal skin Effects 0.000 description 1
- 239000012038 nucleophile Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 230000003287 optical effect Effects 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- LXNAVEXFUKBNMK-UHFFFAOYSA-N palladium(II) acetate Substances [Pd].CC(O)=O.CC(O)=O LXNAVEXFUKBNMK-UHFFFAOYSA-N 0.000 description 1
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- 239000012071 phase Substances 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910000027 potassium carbonate Inorganic materials 0.000 description 1
- NTTOTNSKUYCDAV-UHFFFAOYSA-N potassium hydride Chemical compound [KH] NTTOTNSKUYCDAV-UHFFFAOYSA-N 0.000 description 1
- 229910000105 potassium hydride Inorganic materials 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000003380 propellant Substances 0.000 description 1
- 230000001681 protective effect Effects 0.000 description 1
- 230000017854 proteolysis Effects 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- 230000007017 scission Effects 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 229910052709 silver Chemical class 0.000 description 1
- 239000004332 silver Chemical class 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- CSMWJXBSXGUPGY-UHFFFAOYSA-L sodium dithionate Chemical compound [Na+].[Na+].[O-]S(=O)(=O)S([O-])(=O)=O CSMWJXBSXGUPGY-UHFFFAOYSA-L 0.000 description 1
- 229940075931 sodium dithionate Drugs 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 229940086735 succinate Drugs 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003458 sulfonic acid derivatives Chemical class 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- DQCYGMOBLZGOOP-UHFFFAOYSA-N tert-butyl (ne)-n-[(isoquinolin-3-ylamino)-[(2-methylpropan-2-yl)oxycarbonylamino]methylidene]carbamate Chemical compound C1=CC=C2C=NC(NC(NC(=O)OC(C)(C)C)=NC(=O)OC(C)(C)C)=CC2=C1 DQCYGMOBLZGOOP-UHFFFAOYSA-N 0.000 description 1
- CSOJECDGWHHWRS-UHFFFAOYSA-N tert-butyl n-[(2-methylpropan-2-yl)oxycarbonylcarbamothioyl]carbamate Chemical compound CC(C)(C)OC(=O)NC(=S)NC(=O)OC(C)(C)C CSOJECDGWHHWRS-UHFFFAOYSA-N 0.000 description 1
- UQJXXWHAJKRDKY-UHFFFAOYSA-N tert-butyl n-[[(2-methylpropan-2-yl)oxycarbonylamino]-methylsulfanylmethylidene]carbamate Chemical compound CC(C)(C)OC(=O)NC(SC)=NC(=O)OC(C)(C)C UQJXXWHAJKRDKY-UHFFFAOYSA-N 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- QNMBSXGYAQZCTN-UHFFFAOYSA-N thiophen-3-ylboronic acid Chemical compound OB(O)C=1C=CSC=1 QNMBSXGYAQZCTN-UHFFFAOYSA-N 0.000 description 1
- FYOWZTWVYZOZSI-UHFFFAOYSA-N thiourea dioxide Chemical compound NC(=N)S(O)=O FYOWZTWVYZOZSI-UHFFFAOYSA-N 0.000 description 1
- 230000002885 thrombogenetic effect Effects 0.000 description 1
- 238000013334 tissue model Methods 0.000 description 1
- 125000005147 toluenesulfonyl group Chemical group C=1(C(=CC=CC1)S(=O)(=O)*)C 0.000 description 1
- WRECIMRULFAWHA-UHFFFAOYSA-N trimethyl borate Chemical compound COB(OC)OC WRECIMRULFAWHA-UHFFFAOYSA-N 0.000 description 1
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 1
- 230000002485 urinary effect Effects 0.000 description 1
- 108010065822 urokinase inhibitor Proteins 0.000 description 1
- 239000001993 wax Substances 0.000 description 1
- 230000037314 wound repair Effects 0.000 description 1
- 150000003751 zinc Chemical class 0.000 description 1
Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- 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
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- A—HUMAN NECESSITIES
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- 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
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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
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
- A61P15/08—Drugs for genital or sexual disorders; Contraceptives for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/02—Drugs for dermatological disorders for treating wounds, ulcers, burns, scars, keloids, or the like
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A61P35/04—Antineoplastic agents specific for metastasis
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- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/46—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with hetero atoms directly attached to the ring nitrogen atom
- C07D207/48—Sulfur atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/12—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring
- C07D217/14—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals
- C07D217/16—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with radicals, substituted by hetero atoms, attached to carbon atoms of the nitrogen-containing ring other than aralkyl radicals substituted by oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/24—Oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems 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 carbon atoms of the nitrogen-containing ring
- C07D217/26—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- 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
- 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
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/22—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with hetero atoms directly attached to ring nitrogen atoms
- C07D295/26—Sulfur 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
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
- C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- 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
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Physical Education & Sports Medicine (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Reproductive Health (AREA)
- Pain & Pain Management (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Gynecology & Obstetrics (AREA)
- Pregnancy & Childbirth (AREA)
- Immunology (AREA)
- Endocrinology (AREA)
- Dermatology (AREA)
- Oncology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GBGB9721964.6A GB9721964D0 (en) | 1997-10-16 | 1997-10-16 | Isoquinolines |
PCT/EP1998/006353 WO1999020608A1 (en) | 1997-10-16 | 1998-10-05 | Isoquinolines as urokinase inhibitors |
Publications (1)
Publication Number | Publication Date |
---|---|
HRP20000217A2 true HRP20000217A2 (en) | 2000-10-31 |
Family
ID=10820680
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
HR20000217A HRP20000217A2 (en) | 1997-10-16 | 2000-04-14 | Isoquinolines as urokinase inhibitors |
Country Status (41)
Country | Link |
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US (1) | US6248738B1 (bg) |
EP (1) | EP1023268B1 (bg) |
JP (1) | JP3600794B2 (bg) |
KR (1) | KR20010031163A (bg) |
CN (1) | CN1275979A (bg) |
AP (1) | AP959A (bg) |
AR (1) | AR015964A1 (bg) |
AT (1) | ATE240943T1 (bg) |
AU (1) | AU727315B2 (bg) |
BG (1) | BG104328A (bg) |
BR (1) | BR9812922A (bg) |
CA (1) | CA2306782C (bg) |
CO (1) | CO4990959A1 (bg) |
DE (1) | DE69814894T2 (bg) |
DK (1) | DK1023268T3 (bg) |
DZ (1) | DZ2624A1 (bg) |
EA (1) | EA002632B1 (bg) |
ES (1) | ES2197514T3 (bg) |
GB (1) | GB9721964D0 (bg) |
GT (1) | GT199800159A (bg) |
HN (1) | HN1998000158A (bg) |
HR (1) | HRP20000217A2 (bg) |
HU (1) | HUP0004491A3 (bg) |
ID (1) | ID23913A (bg) |
IL (1) | IL135122A0 (bg) |
IS (1) | IS5412A (bg) |
MA (1) | MA26552A1 (bg) |
NO (1) | NO20001924L (bg) |
NZ (1) | NZ503390A (bg) |
OA (1) | OA11348A (bg) |
PA (1) | PA8461601A1 (bg) |
PE (1) | PE121299A1 (bg) |
PL (1) | PL340035A1 (bg) |
PT (1) | PT1023268E (bg) |
SK (1) | SK4872000A3 (bg) |
TN (1) | TNSN98185A1 (bg) |
TR (1) | TR200001010T2 (bg) |
UY (2) | UY25211A1 (bg) |
WO (1) | WO1999020608A1 (bg) |
YU (1) | YU21100A (bg) |
ZA (1) | ZA989412B (bg) |
Families Citing this family (18)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2000005214A2 (en) * | 1998-07-24 | 2000-02-03 | Pfizer Inc. | Isoquinolines as urokinase inhibitors |
DE19940389A1 (de) | 1999-08-25 | 2001-03-01 | Wilex Biotechnology Gmbh | Selektive Inhibitoren des Urokinase-Plasminogen Aktivators |
ES2172376B1 (es) * | 2000-01-28 | 2003-11-16 | Servier Lab | Nuevos derivados de isoquinoleinas, su procedimiento de preparacion y las composiciones farmaceuticas que los contienen. |
DE10013715A1 (de) * | 2000-03-20 | 2001-09-27 | Wilex Biotechnology Gmbh | Hochselektive Inhibitoren des Urokinase-Plasminogenaktivators |
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