AP959A - Isoquinolines. - Google Patents
Isoquinolines. Download PDFInfo
- Publication number
- AP959A AP959A APAP/P/1998/001366A AP9801366A AP959A AP 959 A AP959 A AP 959A AP 9801366 A AP9801366 A AP 9801366A AP 959 A AP959 A AP 959A
- Authority
- AP
- ARIPO
- Prior art keywords
- alkylene
- optionally substituted
- halogen
- compound
- alkyl optionally
- Prior art date
Links
- 150000002537 isoquinolines Chemical class 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 156
- 150000003839 salts Chemical class 0.000 claims abstract description 66
- 150000002367 halogens Chemical class 0.000 claims description 112
- 229910052736 halogen Inorganic materials 0.000 claims description 111
- 238000002360 preparation method Methods 0.000 claims description 95
- 125000000217 alkyl group Chemical group 0.000 claims description 72
- 239000000203 mixture Substances 0.000 claims description 72
- -1 CH(OH)Ph Chemical group 0.000 claims description 52
- 125000002947 alkylene group Chemical group 0.000 claims description 45
- 238000000034 method Methods 0.000 claims description 41
- 125000001424 substituent group Chemical group 0.000 claims description 41
- 125000003545 alkoxy group Chemical group 0.000 claims description 32
- 125000003118 aryl group Chemical group 0.000 claims description 29
- 229910052794 bromium Inorganic materials 0.000 claims description 26
- 229910052739 hydrogen Inorganic materials 0.000 claims description 25
- 229910052760 oxygen Inorganic materials 0.000 claims description 25
- 238000006243 chemical reaction Methods 0.000 claims description 22
- 125000001072 heteroaryl group Chemical group 0.000 claims description 20
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 14
- 125000002496 methyl group Chemical group [H]C([H])([H])* 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
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- 210000001519 tissue Anatomy 0.000 claims description 12
- 206010028980 Neoplasm Diseases 0.000 claims description 11
- 239000003153 chemical reaction reagent Substances 0.000 claims description 11
- 229920006395 saturated elastomer Polymers 0.000 claims description 11
- 208000025865 Ulcer Diseases 0.000 claims description 10
- 125000004429 atom Chemical group 0.000 claims description 10
- 229910052799 carbon Inorganic materials 0.000 claims description 10
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 10
- 229910052801 chlorine Inorganic materials 0.000 claims description 10
- 238000010511 deprotection reaction Methods 0.000 claims description 10
- 231100000397 ulcer Toxicity 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 9
- 230000033115 angiogenesis Effects 0.000 claims description 8
- 230000015572 biosynthetic process Effects 0.000 claims description 8
- 230000001684 chronic effect 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
- 230000009545 invasion Effects 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
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 7
- 125000005605 benzo group Chemical group 0.000 claims description 7
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 238000011282 treatment Methods 0.000 claims description 7
- 210000004881 tumor cell Anatomy 0.000 claims description 7
- 230000037314 wound repair 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
- 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[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
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 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
- 230000002500 effect on skin 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
- 230000001404 mediated effect Effects 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
- 125000001425 triazolyl group Chemical group 0.000 claims description 6
- FXVHAOFNNRNCRJ-UHFFFAOYSA-N 2-(4-chloro-7-sulfamoylisoquinolin-1-yl)guanidine Chemical compound C1=C(S(N)(=O)=O)C=C2C(NC(=N)N)=NC=C(Cl)C2=C1 FXVHAOFNNRNCRJ-UHFFFAOYSA-N 0.000 claims description 5
- 206010016654 Fibrosis Diseases 0.000 claims description 5
- 206010003246 arthritis Diseases 0.000 claims description 5
- 210000000988 bone and bone Anatomy 0.000 claims description 5
- 125000004432 carbon atom Chemical group C* 0.000 claims description 5
- 230000006378 damage Effects 0.000 claims description 5
- 230000004069 differentiation Effects 0.000 claims description 5
- 230000032692 embryo implantation 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
- 230000002757 inflammatory effect Effects 0.000 claims description 5
- VYCKDIRCVDCQAE-UHFFFAOYSA-N isoquinolin-3-amine Chemical class C1=CC=C2C=NC(N)=CC2=C1 VYCKDIRCVDCQAE-UHFFFAOYSA-N 0.000 claims description 5
- 230000001394 metastastic effect Effects 0.000 claims description 5
- 206010061289 metastatic neoplasm Diseases 0.000 claims description 5
- 210000000056 organ Anatomy 0.000 claims description 5
- 230000016087 ovulation Effects 0.000 claims description 5
- 230000021595 spermatogenesis Effects 0.000 claims description 5
- 210000004291 uterus Anatomy 0.000 claims description 5
- 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
- XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 claims description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 4
- 206010029113 Neovascularisation Diseases 0.000 claims description 4
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 4
- 239000003814 drug Substances 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
- 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
- KLIDCXVFHGNTTM-UHFFFAOYSA-N 2,6-dimethoxyphenol Chemical group COC1=CC=CC(OC)=C1O KLIDCXVFHGNTTM-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
- QABOEPAYXSLSDJ-UHFFFAOYSA-N 2-[4-chloro-7-(cyclopentylsulfamoyl)isoquinolin-1-yl]guanidine Chemical compound C1=C2C(NC(=N)N)=NC=C(Cl)C2=CC=C1S(=O)(=O)NC1CCCC1 QABOEPAYXSLSDJ-UHFFFAOYSA-N 0.000 claims description 3
- 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 3
- 239000002671 adjuvant Substances 0.000 claims description 3
- 150000001409 amidines Chemical class 0.000 claims description 3
- 239000003085 diluting agent Substances 0.000 claims description 3
- 238000006073 displacement reaction Methods 0.000 claims description 3
- IYRMNDOLPONSCJ-UHFFFAOYSA-N isoquinolin-2-ium;chloride Chemical compound Cl.C1=NC=CC2=CC=CC=C21 IYRMNDOLPONSCJ-UHFFFAOYSA-N 0.000 claims description 3
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 3
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical group CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 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
- LBCZLHDJYLATSU-UHFFFAOYSA-N 2-[4-chloro-7-(4-methylpiperazin-1-yl)sulfonylisoquinolin-1-yl]guanidine Chemical compound C1CN(C)CCN1S(=O)(=O)C1=CC=C(C(Cl)=CN=C2NC(N)=N)C2=C1 LBCZLHDJYLATSU-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
- 125000006519 CCH3 Chemical group 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
- 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
- 125000005843 halogen group Chemical group 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
- 239000008194 pharmaceutical composition Substances 0.000 claims description 2
- 229910052717 sulfur Inorganic materials 0.000 claims description 2
- 125000004305 thiazinyl group Chemical group S1NC(=CC=C1)* 0.000 claims description 2
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims 3
- 229910052698 phosphorus Inorganic materials 0.000 claims 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 abstract description 30
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 abstract description 29
- 229960005356 urokinase Drugs 0.000 abstract description 12
- 239000003112 inhibitor Substances 0.000 abstract description 6
- 239000007787 solid Substances 0.000 description 85
- XEKOWRVHYACXOJ-UHFFFAOYSA-N ethyl acetate Substances CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 72
- 239000000243 solution Substances 0.000 description 66
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 55
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 50
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 43
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 40
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 34
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 27
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
- 235000019439 ethyl acetate Nutrition 0.000 description 26
- 239000000741 silica gel Substances 0.000 description 26
- 229910002027 silica gel Inorganic materials 0.000 description 26
- 238000004440 column chromatography Methods 0.000 description 25
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 22
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 239000002904 solvent Substances 0.000 description 22
- 238000005481 NMR spectroscopy Methods 0.000 description 20
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 20
- 239000012267 brine Substances 0.000 description 18
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 18
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 17
- 238000010992 reflux Methods 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
- 229910052757 nitrogen Inorganic materials 0.000 description 14
- 229940012957 plasmin Drugs 0.000 description 14
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 13
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 11
- 238000000921 elemental analysis Methods 0.000 description 11
- 239000000843 powder Substances 0.000 description 11
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 11
- UMSWWSIVPWVJOX-UHFFFAOYSA-N 7-bromo-1-chloroisoquinoline Chemical compound C1=C(Br)C=C2C(Cl)=NC=CC2=C1 UMSWWSIVPWVJOX-UHFFFAOYSA-N 0.000 description 10
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 10
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 229910000104 sodium hydride Inorganic materials 0.000 description 10
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 9
- 239000002253 acid Substances 0.000 description 9
- 238000001914 filtration Methods 0.000 description 9
- 238000007429 general method Methods 0.000 description 9
- 239000003921 oil Substances 0.000 description 9
- 239000000725 suspension Substances 0.000 description 9
- BHJHBXRXPODWGU-UHFFFAOYSA-N 1-[3-(1-aminoisoquinolin-6-yl)-1-oxo-1-piperidin-1-ylpropan-2-yl]-3-[(2,2,5,7,8-pentamethyl-3,4-dihydrochromen-6-yl)sulfonylamino]urea Chemical compound CC=1C=2CCC(C)(C)OC=2C(C)=C(C)C=1S(=O)(=O)NNC(=O)NC(CC=1C=C2C=CN=C(N)C2=CC=1)C(=O)N1CCCCC1 BHJHBXRXPODWGU-UHFFFAOYSA-N 0.000 description 8
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000006071 cream Substances 0.000 description 8
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 8
- 239000006185 dispersion Substances 0.000 description 8
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical compound O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 7
- 239000002480 mineral oil Substances 0.000 description 7
- 235000010446 mineral oil Nutrition 0.000 description 7
- 239000002797 plasminogen activator inhibitor Substances 0.000 description 7
- 238000003786 synthesis reaction Methods 0.000 description 7
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 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
- 210000004027 cell Anatomy 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 229960000789 guanidine hydrochloride Drugs 0.000 description 6
- PJJJBBJSCAKJQF-UHFFFAOYSA-N guanidinium chloride Chemical compound [Cl-].NC(N)=[NH2+] PJJJBBJSCAKJQF-UHFFFAOYSA-N 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- MBXFJGWNDTUZLK-UHFFFAOYSA-N 2-isoquinolin-1-ylguanidine Chemical class C1=CC=C2C(NC(=N)N)=NC=CC2=C1 MBXFJGWNDTUZLK-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 5
- 239000007832 Na2SO4 Substances 0.000 description 5
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 5
- 150000001412 amines Chemical class 0.000 description 5
- 229910021529 ammonia Inorganic materials 0.000 description 5
- 229960004198 guanidine Drugs 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- 239000011541 reaction mixture Substances 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
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- 230000000593 degrading effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 239000007933 dermal patch Substances 0.000 description 1
- 125000000950 dibromo group Chemical group Br* 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- 238000010790 dilution Methods 0.000 description 1
- 239000012895 dilution Substances 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940113088 dimethylacetamide Drugs 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000010410 dusting Methods 0.000 description 1
- 239000000839 emulsion Substances 0.000 description 1
- 210000002889 endothelial cell Anatomy 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- CCIVGXIOQKPBKL-UHFFFAOYSA-M ethanesulfonate Chemical compound CCS([O-])(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-M 0.000 description 1
- WZPBFJCUISVKMO-UHFFFAOYSA-N ethyl 1-chloroisoquinoline-5-carboxylate Chemical compound N1=CC=C2C(C(=O)OCC)=CC=CC2=C1Cl WZPBFJCUISVKMO-UHFFFAOYSA-N 0.000 description 1
- FCZCIXQGZOUIDN-UHFFFAOYSA-N ethyl 2-diethoxyphosphinothioyloxyacetate Chemical compound CCOC(=O)COP(=S)(OCC)OCC FCZCIXQGZOUIDN-UHFFFAOYSA-N 0.000 description 1
- UIPMSQCRENDMKW-UHFFFAOYSA-N ethyl 2-isoquinolin-5-yloxyacetate Chemical compound N1=CC=C2C(OCC(=O)OCC)=CC=CC2=C1 UIPMSQCRENDMKW-UHFFFAOYSA-N 0.000 description 1
- 239000002360 explosive Substances 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229950003499 fibrin Drugs 0.000 description 1
- 210000002950 fibroblast Anatomy 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 229940083094 guanine derivative acting on arteriolar smooth muscle Drugs 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 150000002391 heterocyclic compounds Chemical class 0.000 description 1
- 239000008241 heterogeneous mixture Substances 0.000 description 1
- OCUALGGRTZGVPG-UHFFFAOYSA-N hydrazinylidenemethanesulfonic acid Chemical compound NN=CS(O)(=O)=O OCUALGGRTZGVPG-UHFFFAOYSA-N 0.000 description 1
- 125000001145 hydrido group Chemical group *[H] 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- 239000000416 hydrocolloid Substances 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 239000005457 ice water Substances 0.000 description 1
- 150000002463 imidates Chemical class 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 210000004969 inflammatory cell Anatomy 0.000 description 1
- 229940030980 inova Drugs 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 150000002500 ions Chemical class 0.000 description 1
- VDBNYAPERZTOOF-UHFFFAOYSA-N isoquinolin-1(2H)-one Chemical compound C1=CC=C2C(=O)NC=CC2=C1 VDBNYAPERZTOOF-UHFFFAOYSA-N 0.000 description 1
- 125000004254 isoquinolin-1-yl group Chemical group [H]C1=C([H])C2=C([H])C([H])=C([H])C([H])=C2C(*)=N1 0.000 description 1
- JGMSGABJHLXRRW-UHFFFAOYSA-N isoquinoline-7-carbonitrile Chemical compound C1=CN=CC2=CC(C#N)=CC=C21 JGMSGABJHLXRRW-UHFFFAOYSA-N 0.000 description 1
- 230000000155 isotopic effect Effects 0.000 description 1
- 150000002576 ketones Chemical class 0.000 description 1
- 229940001447 lactate Drugs 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 229940057995 liquid paraffin Drugs 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 1
- CCZVEWRRAVASGL-UHFFFAOYSA-N lithium;2-methanidylpropane Chemical compound [Li+].CC(C)[CH2-] CCZVEWRRAVASGL-UHFFFAOYSA-N 0.000 description 1
- IHLVCKWPAMTVTG-UHFFFAOYSA-N lithium;carbanide Chemical compound [Li+].[CH3-] IHLVCKWPAMTVTG-UHFFFAOYSA-N 0.000 description 1
- 239000006210 lotion Substances 0.000 description 1
- 210000002540 macrophage Anatomy 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 229910052751 metal Inorganic materials 0.000 description 1
- 239000002184 metal Substances 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- LCARMRMLFMRMAA-UHFFFAOYSA-N methyl n'-(4-methoxy-2,3,6-trimethylphenyl)sulfonylcarbamimidothioate Chemical compound COC1=CC(C)=C(S(=O)(=O)N=C(N)SC)C(C)=C1C LCARMRMLFMRMAA-UHFFFAOYSA-N 0.000 description 1
- GLIKYKRDYKKEBJ-UHFFFAOYSA-N methyl n'-nitrocarbamimidate Chemical compound CO\C(N)=N/[N+]([O-])=O GLIKYKRDYKKEBJ-UHFFFAOYSA-N 0.000 description 1
- FLZZNZJENFNFOJ-UHFFFAOYSA-N methyl n'-nitrocarbamimidothioate Chemical compound CSC(N)=N[N+]([O-])=O FLZZNZJENFNFOJ-UHFFFAOYSA-N 0.000 description 1
- KNPNGMXRGITFLE-UHFFFAOYSA-N methylperoxy(phenyl)borinic acid Chemical compound COOB(O)C1=CC=CC=C1 KNPNGMXRGITFLE-UHFFFAOYSA-N 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 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
- 239000012038 nucleophile Substances 0.000 description 1
- JRZJOMJEPLMPRA-UHFFFAOYSA-N olefin Natural products CCCCCCCC=C JRZJOMJEPLMPRA-UHFFFAOYSA-N 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 230000002018 overexpression Effects 0.000 description 1
- 229910052763 palladium Inorganic materials 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
- 238000007911 parenteral administration Methods 0.000 description 1
- 239000012071 phase Substances 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- UXCDUFKZSUBXGM-UHFFFAOYSA-N phosphoric tribromide Chemical compound BrP(Br)(Br)=O UXCDUFKZSUBXGM-UHFFFAOYSA-N 0.000 description 1
- 229920000058 polyacrylate Polymers 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
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 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
- 230000002797 proteolythic effect 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
- 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
- 150000003378 silver Chemical class 0.000 description 1
- 239000010802 sludge Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 210000000329 smooth muscle myocyte Anatomy 0.000 description 1
- 235000017557 sodium bicarbonate Nutrition 0.000 description 1
- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 230000003595 spectral effect Effects 0.000 description 1
- 235000015096 spirit Nutrition 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000007858 starting material 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
- FDDDEECHVMSUSB-UHFFFAOYSA-N sulfanilamide Chemical compound NC1=CC=C(S(N)(=O)=O)C=C1 FDDDEECHVMSUSB-UHFFFAOYSA-N 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- XTHPWXDJESJLNJ-UHFFFAOYSA-N sulfurochloridic acid Chemical compound OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 238000010998 test method Methods 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
- 230000017423 tissue regeneration Effects 0.000 description 1
- 238000011426 transformation method Methods 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
- 108010065822 urokinase inhibitor Proteins 0.000 description 1
- 229940045860 white wax Drugs 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- 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
- 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
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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
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
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- 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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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- 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
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- A—HUMAN NECESSITIES
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- 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
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- 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)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Reproductive Health (AREA)
- Epidemiology (AREA)
- Rheumatology (AREA)
- Physical Education & Sports Medicine (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)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9721964.6A GB9721964D0 (en) | 1997-10-16 | 1997-10-16 | Isoquinolines |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| AP9801366A0 AP9801366A0 (en) | 1998-12-31 |
| AP959A true AP959A (en) | 2001-04-17 |
Family
ID=10820680
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| APAP/P/1998/001366A AP959A (en) | 1997-10-16 | 1998-10-19 | Isoquinolines. |
Country Status (41)
| Country | Link |
|---|---|
| US (1) | US6248738B1 (no) |
| EP (1) | EP1023268B1 (no) |
| JP (1) | JP3600794B2 (no) |
| KR (1) | KR20010031163A (no) |
| CN (1) | CN1275979A (no) |
| AP (1) | AP959A (no) |
| AR (1) | AR015964A1 (no) |
| AT (1) | ATE240943T1 (no) |
| AU (1) | AU727315B2 (no) |
| BG (1) | BG104328A (no) |
| BR (1) | BR9812922A (no) |
| CA (1) | CA2306782C (no) |
| CO (1) | CO4990959A1 (no) |
| DE (1) | DE69814894T2 (no) |
| DK (1) | DK1023268T3 (no) |
| DZ (1) | DZ2624A1 (no) |
| EA (1) | EA002632B1 (no) |
| ES (1) | ES2197514T3 (no) |
| GB (1) | GB9721964D0 (no) |
| GT (1) | GT199800159A (no) |
| HN (1) | HN1998000158A (no) |
| HR (1) | HRP20000217A2 (no) |
| HU (1) | HUP0004491A3 (no) |
| ID (1) | ID23913A (no) |
| IL (1) | IL135122A0 (no) |
| IS (1) | IS5412A (no) |
| MA (1) | MA26552A1 (no) |
| NO (1) | NO20001924L (no) |
| NZ (1) | NZ503390A (no) |
| OA (1) | OA11348A (no) |
| PA (1) | PA8461601A1 (no) |
| PE (1) | PE121299A1 (no) |
| PL (1) | PL340035A1 (no) |
| PT (1) | PT1023268E (no) |
| SK (1) | SK4872000A3 (no) |
| TN (1) | TNSN98185A1 (no) |
| TR (1) | TR200001010T2 (no) |
| UY (2) | UY25211A1 (no) |
| WO (1) | WO1999020608A1 (no) |
| YU (1) | YU21100A (no) |
| ZA (1) | ZA989412B (no) |
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 |
| GB0026490D0 (en) * | 2000-10-30 | 2000-12-13 | Pfizer Ltd | Process |
| ATE415162T1 (de) * | 2001-06-11 | 2008-12-15 | Vertex Pharma | Isochinolin-inhibitoren von p38 |
| EP1549632A4 (en) | 2002-05-28 | 2005-11-09 | Dimensional Pharm Inc | NEW THIOPHENAMIDINE, COMPOSITIONS AND METHOD FOR THE TREATMENT OF COMPLEMENTED DISEASES AND SUFFERING |
| DE60329318D1 (de) * | 2002-11-20 | 2009-10-29 | Japan Tobacco Inc | 4-oxochinolinverbindungen und deren verwendung als hiv-integrase-inhibitoren |
| GB0326964D0 (en) * | 2003-11-19 | 2003-12-24 | Glaxo Group Ltd | Chemical compounds |
| MY134672A (en) * | 2004-05-20 | 2007-12-31 | Japan Tobacco Inc | Stable crystal of 4-oxoquinoline compound |
| WO2005113509A1 (en) * | 2004-05-20 | 2005-12-01 | Japan Tobacco Inc. | Novel 4-oxoquinoline compound and use thereof as hiv integrase inhibitor |
| US7872136B2 (en) | 2005-02-25 | 2011-01-18 | Kowa Co., Ltd. | Process for production of 4-fluoroisoquinoline-5-sulfonyl halide or salt thereof |
| DE602006009257D1 (de) | 2005-06-24 | 2009-10-29 | Wilex Ag | Verwendung von urokinase-inhibitoren zur behandlunklerose (als) |
| BRPI0708685B8 (pt) * | 2006-03-06 | 2021-05-25 | Japan Tobacco Inc | composto de 4-oxoquinolina, seu uso e método para produção dos mesmos |
| TWI795381B (zh) * | 2016-12-21 | 2023-03-11 | 比利時商健生藥品公司 | 作為ｍａｌｔ１抑制劑之吡唑衍生物 |
| CN106831575B (zh) * | 2017-02-13 | 2019-04-16 | 北京六合宁远科技有限公司 | 一种1-氨基异喹啉-6-甲醇的制备方法 |
| CN113877483B (zh) * | 2021-07-20 | 2023-11-24 | 烟台宁远药业有限公司 | 医药中间体卤代异喹啉类硼酸的低温连续合成装置与方法 |
| CN115286573B (zh) * | 2022-08-04 | 2024-12-10 | 常州工程职业技术学院 | 一种1-烷氧基异喹啉化合物的绿色合成方法 |
-
1997
- 1997-10-16 GB GBGB9721964.6A patent/GB9721964D0/en not_active Ceased
-
1998
- 1998-10-05 NZ NZ503390A patent/NZ503390A/en unknown
- 1998-10-05 DE DE69814894T patent/DE69814894T2/de not_active Expired - Fee Related
- 1998-10-05 HR HR20000217A patent/HRP20000217A2/hr not_active Application Discontinuation
- 1998-10-05 JP JP2000516950A patent/JP3600794B2/ja not_active Expired - Fee Related
- 1998-10-05 ES ES98954357T patent/ES2197514T3/es not_active Expired - Lifetime
- 1998-10-05 PT PT98954357T patent/PT1023268E/pt unknown
- 1998-10-05 ID IDW20000691A patent/ID23913A/id unknown
- 1998-10-05 US US09/424,497 patent/US6248738B1/en not_active Expired - Fee Related
- 1998-10-05 WO PCT/EP1998/006353 patent/WO1999020608A1/en not_active Ceased
- 1998-10-05 TR TR2000/01010T patent/TR200001010T2/xx unknown
- 1998-10-05 CA CA002306782A patent/CA2306782C/en not_active Expired - Fee Related
- 1998-10-05 CN CN98810108A patent/CN1275979A/zh active Pending
- 1998-10-05 DK DK98954357T patent/DK1023268T3/da active
- 1998-10-05 HU HU0004491A patent/HUP0004491A3/hu unknown
- 1998-10-05 PL PL98340035A patent/PL340035A1/xx unknown
- 1998-10-05 AU AU11508/99A patent/AU727315B2/en not_active Ceased
- 1998-10-05 IL IL13512298A patent/IL135122A0/xx unknown
- 1998-10-05 KR KR1020007004083A patent/KR20010031163A/ko not_active Abandoned
- 1998-10-05 BR BR9812922-8A patent/BR9812922A/pt not_active Application Discontinuation
- 1998-10-05 EP EP98954357A patent/EP1023268B1/en not_active Expired - Lifetime
- 1998-10-05 SK SK487-2000A patent/SK4872000A3/sk unknown
- 1998-10-05 EA EA200000320A patent/EA002632B1/ru not_active IP Right Cessation
- 1998-10-05 YU YU21100A patent/YU21100A/sh unknown
- 1998-10-05 AT AT98954357T patent/ATE240943T1/de not_active IP Right Cessation
- 1998-10-08 HN HN1998000158A patent/HN1998000158A/es unknown
- 1998-10-09 GT GT199800159A patent/GT199800159A/es unknown
- 1998-10-12 PA PA19988461601A patent/PA8461601A1/es unknown
- 1998-10-14 MA MA25298A patent/MA26552A1/fr unknown
- 1998-10-14 DZ DZ980234A patent/DZ2624A1/xx active
- 1998-10-14 TN TNTNSN98185A patent/TNSN98185A1/fr unknown
- 1998-10-14 AR ARP980105113A patent/AR015964A1/es not_active Application Discontinuation
- 1998-10-15 ZA ZA9809412A patent/ZA989412B/xx unknown
- 1998-10-15 PE PE1998000973A patent/PE121299A1/es not_active Application Discontinuation
- 1998-10-15 UY UY25211A patent/UY25211A1/es unknown
- 1998-10-16 CO CO98060365A patent/CO4990959A1/es unknown
- 1998-10-19 AP APAP/P/1998/001366A patent/AP959A/en active
- 1998-12-08 UY UY25291A patent/UY25291A1/es not_active IP Right Cessation
-
2000
- 2000-03-21 IS IS5412A patent/IS5412A/is unknown
- 2000-04-07 OA OA1200000102A patent/OA11348A/en unknown
- 2000-04-11 BG BG104328A patent/BG104328A/bg unknown
- 2000-04-13 NO NO20001924A patent/NO20001924L/no unknown
Non-Patent Citations (1)
| Title |
|---|
| JOURNAL OF MEDICINAL CHEMISTRY., vol. 33, no. 11, 1990, pages 2956-2961 * |
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