NO311129B1 - Aromatiske forbindelser, anvendelse derav og farmasöytiske blandinger inneholdende dem - Google Patents
Aromatiske forbindelser, anvendelse derav og farmasöytiske blandinger inneholdende dem Download PDFInfo
- Publication number
- NO311129B1 NO311129B1 NO19975985A NO975985A NO311129B1 NO 311129 B1 NO311129 B1 NO 311129B1 NO 19975985 A NO19975985 A NO 19975985A NO 975985 A NO975985 A NO 975985A NO 311129 B1 NO311129 B1 NO 311129B1
- Authority
- NO
- Norway
- Prior art keywords
- alkyl
- ethylamino
- bromo
- pyridazine
- benzyl
- Prior art date
Links
- 239000008194 pharmaceutical composition Substances 0.000 title description 4
- 150000001491 aromatic compounds Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims description 166
- -1 hydroxy, amino Chemical group 0.000 claims description 119
- 125000000217 alkyl group Chemical group 0.000 claims description 86
- 239000000203 mixture Substances 0.000 claims description 49
- 229910052736 halogen Inorganic materials 0.000 claims description 35
- 150000002367 halogens Chemical class 0.000 claims description 35
- 239000001257 hydrogen Substances 0.000 claims description 27
- 229910052739 hydrogen Inorganic materials 0.000 claims description 27
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 27
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 26
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 23
- 150000002148 esters Chemical class 0.000 claims description 22
- 125000001424 substituent group Chemical group 0.000 claims description 22
- 208000002193 Pain Diseases 0.000 claims description 21
- DMYLUKNFEYWGCH-UHFFFAOYSA-N pyridazine-3-carboxamide Chemical compound NC(=O)C1=CC=CN=N1 DMYLUKNFEYWGCH-UHFFFAOYSA-N 0.000 claims description 21
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 20
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- RUUOPSRRIKJHNH-UHFFFAOYSA-N pyridazine-3-carboxylic acid Chemical compound OC(=O)C1=CC=CN=N1 RUUOPSRRIKJHNH-UHFFFAOYSA-N 0.000 claims description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 18
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 17
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 16
- 229910052757 nitrogen Inorganic materials 0.000 claims description 16
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 14
- XIUVRDRLZYFQCI-UHFFFAOYSA-N 6-[[5-bromo-2-(cyclopropylmethoxy)phenyl]methyl-ethylamino]pyridazine-3-carboxylic acid Chemical group C=1C=C(C(O)=O)N=NC=1N(CC)CC1=CC(Br)=CC=C1OCC1CC1 XIUVRDRLZYFQCI-UHFFFAOYSA-N 0.000 claims description 13
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 13
- 125000004432 carbon atom Chemical group C* 0.000 claims description 13
- 125000000623 heterocyclic group Chemical group 0.000 claims description 13
- 125000003545 alkoxy group Chemical group 0.000 claims description 12
- 238000001727 in vivo Methods 0.000 claims description 11
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 11
- 125000003282 alkyl amino group Chemical group 0.000 claims description 10
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 10
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 10
- 150000002431 hydrogen Chemical class 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 239000001301 oxygen Substances 0.000 claims description 10
- 125000001544 thienyl group Chemical group 0.000 claims description 10
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 9
- 150000001408 amides Chemical class 0.000 claims description 9
- 125000002098 pyridazinyl group Chemical group 0.000 claims description 9
- 125000004076 pyridyl group Chemical group 0.000 claims description 9
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 8
- 125000000335 thiazolyl group Chemical group 0.000 claims description 8
- 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 7
- 125000001072 heteroaryl group Chemical group 0.000 claims description 7
- 125000002971 oxazolyl group Chemical group 0.000 claims description 7
- 150000003536 tetrazoles Chemical class 0.000 claims description 7
- ZWMUNUOJAOFVHX-UHFFFAOYSA-N 6-[[5-bromo-2-(3,3,3-trifluoro-2-hydroxypropoxy)phenyl]methyl-ethylamino]pyridazine-3-carboxylic acid Chemical compound C=1C=C(C(O)=O)N=NC=1N(CC)CC1=CC(Br)=CC=C1OCC(O)C(F)(F)F ZWMUNUOJAOFVHX-UHFFFAOYSA-N 0.000 claims description 6
- VZDUVYKVJJHFGC-UHFFFAOYSA-N 6-[[5-chloro-2-(cyclopropylmethoxy)phenyl]methyl-ethylamino]pyridazine-3-carboxamide Chemical compound C=1C=C(C(N)=O)N=NC=1N(CC)CC1=CC(Cl)=CC=C1OCC1CC1 VZDUVYKVJJHFGC-UHFFFAOYSA-N 0.000 claims description 6
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 6
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 6
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 6
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 6
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 6
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
- 125000006413 ring segment Chemical group 0.000 claims description 6
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 6
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 5
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 5
- 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 4
- 125000005647 linker group Chemical group 0.000 claims description 4
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 229910052717 sulfur Chemical group 0.000 claims description 4
- 239000011593 sulfur Chemical group 0.000 claims description 4
- 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- JJLIONLDXUJJOW-UHFFFAOYSA-N 5-[(2,5-dimethoxyphenyl)methylamino]-2-hydroxybenzoic acid Chemical compound COC1=CC=C(OC)C(CNC=2C=C(C(O)=CC=2)C(O)=O)=C1 JJLIONLDXUJJOW-UHFFFAOYSA-N 0.000 claims description 3
- GMMBETCEGBXFIY-UHFFFAOYSA-N 6-[(2-methoxyphenyl)methylamino]pyridine-3-carboxylic acid Chemical compound COC1=CC=CC=C1CNC1=CC=C(C(O)=O)C=N1 GMMBETCEGBXFIY-UHFFFAOYSA-N 0.000 claims description 3
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 3
- 125000000539 amino acid group Chemical group 0.000 claims description 3
- 125000001589 carboacyl group Chemical group 0.000 claims description 3
- 125000002883 imidazolyl group Chemical group 0.000 claims description 3
- 125000005322 morpholin-1-yl group Chemical group 0.000 claims description 3
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 3
- 125000005344 pyridylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 2
- WELGATNESZMLPG-UHFFFAOYSA-N 2-chloro-5-[(2,3-dimethoxyphenyl)methylamino]-3-sulfamoylbenzoic acid Chemical compound COC1=CC=CC(CNC=2C=C(C(Cl)=C(C(O)=O)C=2)S(N)(=O)=O)=C1OC WELGATNESZMLPG-UHFFFAOYSA-N 0.000 claims description 2
- NEAQRZUHTPSBBM-UHFFFAOYSA-N 2-hydroxy-3,3-dimethyl-7-nitro-4h-isoquinolin-1-one Chemical compound C1=C([N+]([O-])=O)C=C2C(=O)N(O)C(C)(C)CC2=C1 NEAQRZUHTPSBBM-UHFFFAOYSA-N 0.000 claims description 2
- IKNZBNHVVQIRTO-UHFFFAOYSA-N 2h-tetrazole-5-carboxylic acid Chemical compound OC(=O)C=1N=NNN=1 IKNZBNHVVQIRTO-UHFFFAOYSA-N 0.000 claims description 2
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 claims description 2
- 150000001204 N-oxides Chemical class 0.000 claims description 2
- 125000004423 acyloxy group Chemical group 0.000 claims description 2
- 150000003857 carboxamides Chemical class 0.000 claims description 2
- PGRHXDWITVMQBC-UHFFFAOYSA-N dehydroacetic acid Natural products CC(=O)C1C(=O)OC(C)=CC1=O PGRHXDWITVMQBC-UHFFFAOYSA-N 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000005842 heteroatom Chemical group 0.000 claims description 2
- RCCPEORTSYDPMB-UHFFFAOYSA-N hydroxy benzenecarboximidothioate Chemical compound OSC(=N)C1=CC=CC=C1 RCCPEORTSYDPMB-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- LLAMBAMNQBTXOO-UHFFFAOYSA-N n-[[5-bromo-2-(cyclopropylmethoxy)phenyl]methyl]-n-ethyl-6-(2h-tetrazol-5-yl)pyridazin-3-amine Chemical compound C=1C=C(C=2NN=NN=2)N=NC=1N(CC)CC1=CC(Br)=CC=C1OCC1CC1 LLAMBAMNQBTXOO-UHFFFAOYSA-N 0.000 claims description 2
- PEQJBOMPGWYIRO-UHFFFAOYSA-N n-ethyl-3,4-dimethoxyaniline Chemical compound CCNC1=CC=C(OC)C(OC)=C1 PEQJBOMPGWYIRO-UHFFFAOYSA-N 0.000 claims description 2
- 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 2
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims 2
- XHJGWSCVFJSARY-UHFFFAOYSA-N 6-[(5-bromo-2-propoxyphenyl)methyl-ethylamino]-n-propylpyridazine-3-carboxamide Chemical compound N1=NC(C(=O)NCCC)=CC=C1N(CC)CC1=CC(Br)=CC=C1OCCC XHJGWSCVFJSARY-UHFFFAOYSA-N 0.000 claims 1
- ADCIPJAKISDYKT-UHFFFAOYSA-N 6-[[5-bromo-2-(2-methylpropoxy)phenyl]methyl-ethylamino]-n-[(3,5-dimethyl-1,2-oxazol-4-yl)sulfonyl]pyridazine-3-carboxamide Chemical compound C=1C=C(C(=O)NS(=O)(=O)C2=C(ON=C2C)C)N=NC=1N(CC)CC1=CC(Br)=CC=C1OCC(C)C ADCIPJAKISDYKT-UHFFFAOYSA-N 0.000 claims 1
- VLPVTBMFQIQCRR-UHFFFAOYSA-N 6-[[5-bromo-2-(cyclopentylmethoxy)phenyl]methyl-ethylamino]pyridine-3-carboxylic acid Chemical compound C=1C=C(C(O)=O)C=NC=1N(CC)CC1=CC(Br)=CC=C1OCC1CCCC1 VLPVTBMFQIQCRR-UHFFFAOYSA-N 0.000 claims 1
- HHWZQCBRLCZKSO-UHFFFAOYSA-N 6-[[5-bromo-2-(cyclopropylmethoxy)phenyl]methyl-ethylamino]pyridine-3-carboxylic acid Chemical compound C=1C=C(C(O)=O)C=NC=1N(CC)CC1=CC(Br)=CC=C1OCC1CC1 HHWZQCBRLCZKSO-UHFFFAOYSA-N 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 claims 1
- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
- IISVYLICOYGZAR-UHFFFAOYSA-N n-[(5-bromo-2-propoxyphenyl)methyl]-n-ethyl-6-(2h-tetrazol-5-yl)pyridazin-3-amine Chemical compound CCCOC1=CC=C(Br)C=C1CN(CC)C1=CC=C(C=2NN=NN=2)N=N1 IISVYLICOYGZAR-UHFFFAOYSA-N 0.000 claims 1
- QHGGDMKTVMQGTL-UHFFFAOYSA-N n-[[2-(cyclopropylmethoxy)-5-methylsulfonylphenyl]methyl]-n-ethyl-6-(2h-tetrazol-5-yl)pyridazin-3-amine Chemical compound C=1C=C(C=2NN=NN=2)N=NC=1N(CC)CC1=CC(S(C)(=O)=O)=CC=C1OCC1CC1 QHGGDMKTVMQGTL-UHFFFAOYSA-N 0.000 claims 1
- FYYWQGDNMOZWLL-UHFFFAOYSA-N n-[[5-chloro-2-(cyclopropylmethoxy)phenyl]methyl]-n-ethyl-6-(2h-tetrazol-5-yl)pyridazin-3-amine Chemical compound C=1C=C(C=2NN=NN=2)N=NC=1N(CC)CC1=CC(Cl)=CC=C1OCC1CC1 FYYWQGDNMOZWLL-UHFFFAOYSA-N 0.000 claims 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 claims 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 133
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 123
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 67
- 239000000243 solution Substances 0.000 description 67
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 63
- 238000006243 chemical reaction Methods 0.000 description 60
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 59
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 50
- 238000000034 method Methods 0.000 description 50
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 45
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 45
- 239000007787 solid Substances 0.000 description 37
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 26
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 25
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 24
- 239000000047 product Substances 0.000 description 24
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 22
- 235000011121 sodium hydroxide Nutrition 0.000 description 21
- 239000000460 chlorine Substances 0.000 description 20
- 239000012044 organic layer Substances 0.000 description 19
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 18
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 18
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 17
- 239000011541 reaction mixture Substances 0.000 description 17
- 229920006395 saturated elastomer Polymers 0.000 description 17
- 229960000583 acetic acid Drugs 0.000 description 16
- 238000000921 elemental analysis Methods 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 16
- 239000012267 brine Substances 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 15
- 239000002904 solvent Substances 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 14
- 239000003921 oil Substances 0.000 description 14
- 235000019198 oils Nutrition 0.000 description 14
- 125000002252 acyl group Chemical group 0.000 description 13
- 229910052786 argon Inorganic materials 0.000 description 13
- 239000002585 base Substances 0.000 description 13
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
- 238000003820 Medium-pressure liquid chromatography Methods 0.000 description 12
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 12
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 12
- 229910052794 bromium Inorganic materials 0.000 description 12
- 229910000027 potassium carbonate Inorganic materials 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- SIGLSFHKYOINAE-UHFFFAOYSA-N 6-[(5-bromo-2-propoxyphenyl)methyl-ethylamino]pyridazine-3-carboxylic acid Chemical compound CCCOC1=CC=C(Br)C=C1CN(CC)C1=CC=C(C(O)=O)N=N1 SIGLSFHKYOINAE-UHFFFAOYSA-N 0.000 description 11
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 238000012360 testing method Methods 0.000 description 11
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- 229910052801 chlorine Inorganic materials 0.000 description 10
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 10
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 10
- 125000006239 protecting group Chemical group 0.000 description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 9
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 239000000284 extract Substances 0.000 description 9
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 9
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 8
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 8
- 235000019270 ammonium chloride Nutrition 0.000 description 8
- 239000003480 eluent Substances 0.000 description 8
- 239000006260 foam Substances 0.000 description 8
- 210000003405 ileum Anatomy 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 238000003786 synthesis reaction Methods 0.000 description 8
- 238000004809 thin layer chromatography Methods 0.000 description 8
- PVNIIMVLHYAWGP-UHFFFAOYSA-N Niacin Chemical compound OC(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-N 0.000 description 7
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 238000004587 chromatography analysis Methods 0.000 description 7
- LDZABGNKWYFWFH-UHFFFAOYSA-N methyl 6-[(5-bromo-2-propoxyphenyl)methyl-ethylamino]pyridine-3-carboxylate Chemical compound CCCOC1=CC=C(Br)C=C1CN(CC)C1=CC=C(C(=O)OC)C=N1 LDZABGNKWYFWFH-UHFFFAOYSA-N 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 239000012279 sodium borohydride Substances 0.000 description 7
- 229910000033 sodium borohydride Inorganic materials 0.000 description 7
- AFABGHUZZDYHJO-UHFFFAOYSA-N 2-Methylpentane Chemical compound CCCC(C)C AFABGHUZZDYHJO-UHFFFAOYSA-N 0.000 description 6
- NMCKZYHQHAZHIO-UHFFFAOYSA-N 6-chloropyridazine-3-carboxamide Chemical compound NC(=O)C1=CC=C(Cl)N=N1 NMCKZYHQHAZHIO-UHFFFAOYSA-N 0.000 description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- WVDDGKGOMKODPV-UHFFFAOYSA-N Benzyl alcohol Chemical compound OCC1=CC=CC=C1 WVDDGKGOMKODPV-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
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- XXSLZJZUSYNITM-UHFFFAOYSA-N tetrabutylammonium tribromide Chemical compound Br[Br-]Br.CCCC[N+](CCCC)(CCCC)CCCC XXSLZJZUSYNITM-UHFFFAOYSA-N 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
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- UPSPUYADGBWSHF-UHFFFAOYSA-N tolmetin Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC=C(CC(O)=O)N1C UPSPUYADGBWSHF-UHFFFAOYSA-N 0.000 description 1
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- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/79—Acids; Esters
- C07D213/80—Acids; Esters in position 3
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- 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]
-
- 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
- C07D237/00—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings
- C07D237/02—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings
- C07D237/06—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members
- C07D237/10—Heterocyclic compounds containing 1,2-diazine or hydrogenated 1,2-diazine rings not condensed with other rings having three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D237/24—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
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings 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
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
- Pyridine Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9512476.4A GB9512476D0 (en) | 1995-06-20 | 1995-06-20 | Aromatic compounds |
| GBGB9601462.6A GB9601462D0 (en) | 1996-01-25 | 1996-01-25 | Aromatic compounds |
| GBGB9606831.7A GB9606831D0 (en) | 1996-03-30 | 1996-03-30 | Aromatic compounds |
| PCT/GB1996/001442 WO1997000863A1 (en) | 1995-06-20 | 1996-06-17 | Aromatic compounds and pharmaceutical compositions containing them |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO975985D0 NO975985D0 (no) | 1997-12-19 |
| NO975985L NO975985L (no) | 1997-12-19 |
| NO311129B1 true NO311129B1 (no) | 2001-10-15 |
Family
ID=27267781
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19975985A NO311129B1 (no) | 1995-06-20 | 1997-12-19 | Aromatiske forbindelser, anvendelse derav og farmasöytiske blandinger inneholdende dem |
Country Status (29)
| Country | Link |
|---|---|
| US (2) | US5994353A (ja) |
| EP (1) | EP0835246B1 (ja) |
| JP (1) | JP3949166B2 (ja) |
| KR (1) | KR19990023006A (ja) |
| CN (1) | CN1193963A (ja) |
| AR (1) | AR004495A1 (ja) |
| AT (1) | ATE207468T1 (ja) |
| AU (1) | AU700337B2 (ja) |
| BG (1) | BG63777B1 (ja) |
| BR (1) | BR9608956A (ja) |
| CA (1) | CA2220925A1 (ja) |
| CZ (1) | CZ290923B6 (ja) |
| DE (1) | DE69616323T2 (ja) |
| DK (1) | DK0835246T3 (ja) |
| EE (1) | EE9700341A (ja) |
| ES (1) | ES2165505T3 (ja) |
| HR (1) | HRP960288B1 (ja) |
| HU (1) | HUP9802317A3 (ja) |
| IL (1) | IL118664A (ja) |
| MX (1) | MX9710218A (ja) |
| MY (1) | MY116531A (ja) |
| NO (1) | NO311129B1 (ja) |
| NZ (1) | NZ311082A (ja) |
| PL (1) | PL324205A1 (ja) |
| PT (1) | PT835246E (ja) |
| RO (1) | RO119945B1 (ja) |
| SK (1) | SK282450B6 (ja) |
| TW (1) | TW434240B (ja) |
| WO (1) | WO1997000863A1 (ja) |
Families Citing this family (42)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB9514160D0 (en) * | 1994-07-25 | 1995-09-13 | Zeneca Ltd | Aromatic compounds |
| GB9417532D0 (en) * | 1994-08-31 | 1994-10-19 | Zeneca Ltd | Aromatic compounds |
| TW434240B (en) * | 1995-06-20 | 2001-05-16 | Zeneca Ltd | Aromatic compounds, preparation thereof and pharmaceutical composition comprising same |
| TW502026B (en) * | 1995-06-20 | 2002-09-11 | Zeneca Ltd | Aromatic compounds useful as antagonists of e-type prostaglandins, processes for the preparation thereof, pharmaceutical compositions comprising the compounds, and intermediates |
| US5834468A (en) * | 1995-07-07 | 1998-11-10 | Zeneca Limited | Substituted aryl and heteroaryl compounds as E-type prostaglandin antagonists |
| US6242474B1 (en) | 1997-06-27 | 2001-06-05 | Fujisawa Pharmaceutical Co., Ltd. | Aromatic ring derivatives |
| GB9903476D0 (en) * | 1999-02-17 | 1999-04-07 | Zeneca Ltd | Therapeutic agents |
| SE0100873D0 (sv) * | 2001-03-13 | 2001-03-13 | Astrazeneca Ab | Method of treatment |
| EP1369129A4 (en) * | 2001-03-14 | 2005-08-03 | Ono Pharmaceutical Co | ANTIDEPRESSOR REMEDIES CONTAINING AN EP1 ANTAGONIST AS ACTIVE INGREDIENT |
| WO2003035064A1 (en) | 2001-10-23 | 2003-05-01 | Applied Research Systems Ars Holding N.V. | Pyrazolidinone compounds as ligands of the prostaglandin ep2 and/or ep4 receptors |
| WO2003043655A1 (fr) * | 2001-11-19 | 2003-05-30 | Ono Pharmaceutical Co., Ltd. | Remedes pour la frequence urinaire |
| ATE455758T1 (de) | 2001-12-20 | 2010-02-15 | Merck Serono Sa | Pyrrolidin-derivatie als prostaglandin- modulatoren |
| WO2003103604A2 (en) | 2002-06-01 | 2003-12-18 | Applied Research Systems Ars Holding N.V | Gamma lactams as prostaglandin agonists and use thereof |
| US7696243B2 (en) | 2004-12-06 | 2010-04-13 | Merck Serono, S.A. | Pyrrolidin-2-one derivatives for use as DP1 receptor agonists |
| ES2321535T3 (es) | 2004-12-23 | 2009-06-08 | Glaxo Group Limited | Compuestos de piridina para el tratamiento de enfermedades mediadas por prostaglandinas. |
| US7767710B2 (en) * | 2005-05-25 | 2010-08-03 | Calosyn Pharma, Inc. | Method for treating osteoarthritis |
| US20060269579A1 (en) * | 2005-05-25 | 2006-11-30 | Musculoskeletal Research Llc | Compositions for treating osteoarthritis |
| ES2437323T3 (es) | 2007-02-16 | 2014-01-10 | Ono Pharmaceutical Co., Ltd. | Agente terapéutico para trastornos de la micción |
| US20090163440A1 (en) * | 2007-09-26 | 2009-06-25 | Waddell David D | Ion-Channel Regulator Compositions and Methods of Using Same |
| AR081626A1 (es) | 2010-04-23 | 2012-10-10 | Cytokinetics Inc | Compuestos amino-piridazinicos, composiciones farmaceuticas que los contienen y uso de los mismos para tratar trastornos musculares cardiacos y esqueleticos |
| AR081331A1 (es) | 2010-04-23 | 2012-08-08 | Cytokinetics Inc | Amino- pirimidinas composiciones de las mismas y metodos para el uso de los mismos |
| US9133123B2 (en) | 2010-04-23 | 2015-09-15 | Cytokinetics, Inc. | Certain amino-pyridines and amino-triazines, compositions thereof, and methods for their use |
| US8759380B2 (en) | 2011-04-22 | 2014-06-24 | Cytokinetics, Inc. | Certain heterocycles, compositions thereof, and methods for their use |
| HUE035069T2 (en) | 2011-12-28 | 2018-05-02 | Global Blood Therapeutics Inc | Substituted benzaldehyde compounds and their use to increase tissue oxygenation |
| WO2013102145A1 (en) | 2011-12-28 | 2013-07-04 | Global Blood Therapeutics, Inc. | Substituted heteroaryl aldehyde compounds and methods for their use in increasing tissue oxygenation |
| US8952171B2 (en) | 2013-03-15 | 2015-02-10 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US10266551B2 (en) | 2013-03-15 | 2019-04-23 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9458139B2 (en) | 2013-03-15 | 2016-10-04 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| US9802900B2 (en) | 2013-03-15 | 2017-10-31 | Global Blood Therapeutics, Inc. | Bicyclic heteroaryl compounds and uses thereof for the modulation of hemoglobin |
| US9604999B2 (en) | 2013-03-15 | 2017-03-28 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| PE20161035A1 (es) | 2013-03-15 | 2016-11-13 | Global Blood Therapeutics Inc | Compuestos y usos de estos para la modulacion de la hemoglobina |
| US10100043B2 (en) | 2013-03-15 | 2018-10-16 | Global Blood Therapeutics, Inc. | Substituted aldehyde compounds and methods for their use in increasing tissue oxygenation |
| US9422279B2 (en) | 2013-03-15 | 2016-08-23 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| KR20150132146A (ko) | 2013-03-15 | 2015-11-25 | 글로벌 블러드 테라퓨틱스, 인크. | 헤모글로빈 조정을 위한 화합물 및 이의 용도 |
| CA2903022C (en) | 2013-03-15 | 2021-11-09 | Global Blood Therapeutics, Inc. | Compounds and uses thereof for the modulation of hemoglobin |
| EA201992707A1 (ru) | 2013-11-18 | 2020-06-30 | Глобал Блад Терапьютикс, Инк. | Соединения и их применения для модуляции гемоглобина |
| JP6809681B2 (ja) | 2014-02-07 | 2021-01-06 | グローバル ブラッド セラピューティクス インコーポレイテッド | ２−ヒドロキシ−６−（（２−（１−イソプロピル−１ｈ−ピラゾール−５−イル）ピリジン−３−イル）メトキシ）ベンズアルデヒドの遊離塩基の結晶多形 |
| MA41841A (fr) | 2015-03-30 | 2018-02-06 | Global Blood Therapeutics Inc | Composés aldéhyde pour le traitement de la fibrose pulmonaire, de l'hypoxie, et de maladies auto-immunes et des tissus conjonctifs |
| TW201731509A (zh) | 2015-12-04 | 2017-09-16 | 全球血液治療公司 | 針對２-羥基-６-（（２-（１-異丙基-１ｈ-吡唑-５-基）吡啶-３-基）甲氧基）-苯甲醛之劑量方案 |
| TWI663160B (zh) | 2016-05-12 | 2019-06-21 | 全球血液治療公司 | 用於合成2-羥基-6-((2-(1-異丙基-1h-吡唑-5-基)-吡啶-3-基)甲氧基)苯甲醛之方法 |
| TW202332423A (zh) | 2016-10-12 | 2023-08-16 | 美商全球血液治療公司 | 包含2-羥基-6-((2-(1-異丙基-1h-吡唑-5-基)吡啶-3-基)甲氧基)-苯甲醛之片劑 |
| EP3860975B1 (en) | 2018-10-01 | 2023-10-18 | Global Blood Therapeutics, Inc. | Modulators of hemoglobin for the treatment of sickle cell disease |
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| US4206145A (en) * | 1976-02-11 | 1980-06-03 | Beecham Group Limited | Hypolipidaemic compounds and compositions |
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| GB9417532D0 (en) * | 1994-08-31 | 1994-10-19 | Zeneca Ltd | Aromatic compounds |
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| TW502026B (en) * | 1995-06-20 | 2002-09-11 | Zeneca Ltd | Aromatic compounds useful as antagonists of e-type prostaglandins, processes for the preparation thereof, pharmaceutical compositions comprising the compounds, and intermediates |
| US5834468A (en) * | 1995-07-07 | 1998-11-10 | Zeneca Limited | Substituted aryl and heteroaryl compounds as E-type prostaglandin antagonists |
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-
1996
- 1996-06-12 TW TW085107056A patent/TW434240B/zh not_active IP Right Cessation
- 1996-06-16 IL IL11866496A patent/IL118664A/en not_active IP Right Cessation
- 1996-06-17 BR BR9608956A patent/BR9608956A/pt not_active Application Discontinuation
- 1996-06-17 RO RO97-02367A patent/RO119945B1/ro unknown
- 1996-06-17 US US08/973,887 patent/US5994353A/en not_active Expired - Fee Related
- 1996-06-17 NZ NZ311082A patent/NZ311082A/xx unknown
- 1996-06-17 DE DE69616323T patent/DE69616323T2/de not_active Expired - Fee Related
- 1996-06-17 EP EP96920936A patent/EP0835246B1/en not_active Expired - Lifetime
- 1996-06-17 EE EE9700341A patent/EE9700341A/xx unknown
- 1996-06-17 KR KR1019970709476A patent/KR19990023006A/ko not_active Application Discontinuation
- 1996-06-17 PL PL96324205A patent/PL324205A1/xx unknown
- 1996-06-17 AU AU62320/96A patent/AU700337B2/en not_active Ceased
- 1996-06-17 HU HU9802317A patent/HUP9802317A3/hu unknown
- 1996-06-17 PT PT96920936T patent/PT835246E/pt unknown
- 1996-06-17 CN CN96196398A patent/CN1193963A/zh active Pending
- 1996-06-17 JP JP50365397A patent/JP3949166B2/ja not_active Expired - Fee Related
- 1996-06-17 DK DK96920936T patent/DK0835246T3/da active
- 1996-06-17 CA CA002220925A patent/CA2220925A1/en not_active Abandoned
- 1996-06-17 SK SK1732-97A patent/SK282450B6/sk unknown
- 1996-06-17 MX MX9710218A patent/MX9710218A/es not_active IP Right Cessation
- 1996-06-17 AT AT96920936T patent/ATE207468T1/de not_active IP Right Cessation
- 1996-06-17 ES ES96920936T patent/ES2165505T3/es not_active Expired - Lifetime
- 1996-06-17 CZ CZ19974109A patent/CZ290923B6/cs not_active IP Right Cessation
- 1996-06-17 WO PCT/GB1996/001442 patent/WO1997000863A1/en not_active Application Discontinuation
- 1996-06-18 HR HR960288A patent/HRP960288B1/xx not_active IP Right Cessation
- 1996-06-18 MY MYPI96002451A patent/MY116531A/en unknown
- 1996-06-20 AR ARP960103226A patent/AR004495A1/es not_active Application Discontinuation
-
1997
- 1997-12-19 NO NO19975985A patent/NO311129B1/no unknown
-
1998
- 1998-01-09 BG BG102173A patent/BG63777B1/bg unknown
-
1999
- 1999-09-13 US US09/395,229 patent/US6365603B1/en not_active Expired - Fee Related
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