ES2331457T3 - Agonistas de beta2-adrenoceptor. - Google Patents
Agonistas de beta2-adrenoceptor. Download PDFInfo
- Publication number
- ES2331457T3 ES2331457T3 ES00935163T ES00935163T ES2331457T3 ES 2331457 T3 ES2331457 T3 ES 2331457T3 ES 00935163 T ES00935163 T ES 00935163T ES 00935163 T ES00935163 T ES 00935163T ES 2331457 T3 ES2331457 T3 ES 2331457T3
- Authority
- ES
- Spain
- Prior art keywords
- hydroxy
- indan
- ethyl
- alkyl
- hydrogen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Lifetime
Links
- 102000014974 beta2-adrenergic receptor activity proteins Human genes 0.000 title claims description 7
- 108040006828 beta2-adrenergic receptor activity proteins Proteins 0.000 title claims description 7
- 239000000556 agonist Substances 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 129
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 96
- 239000001257 hydrogen Substances 0.000 claims abstract description 94
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 50
- 239000000203 mixture Substances 0.000 claims abstract description 48
- -1 cyano, hydroxy Chemical group 0.000 claims abstract description 46
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 36
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 26
- 150000003839 salts Chemical group 0.000 claims abstract description 23
- 239000012453 solvate Chemical group 0.000 claims abstract description 20
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 14
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 14
- 125000005842 heteroatom Chemical group 0.000 claims abstract description 12
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 11
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 9
- 150000002367 halogens Chemical group 0.000 claims abstract description 9
- 125000000027 (C1-C10) alkoxy group Chemical group 0.000 claims abstract description 8
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 5
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims abstract description 3
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 108
- 238000000034 method Methods 0.000 claims description 97
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 47
- 150000002431 hydrogen Chemical group 0.000 claims description 44
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 36
- 238000002360 preparation method Methods 0.000 claims description 29
- 238000011282 treatment Methods 0.000 claims description 19
- 239000002253 acid Substances 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 230000000414 obstructive effect Effects 0.000 claims description 11
- 230000002757 inflammatory effect Effects 0.000 claims description 10
- 230000008569 process Effects 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 8
- 201000010099 disease Diseases 0.000 claims description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 7
- 229940079593 drug Drugs 0.000 claims description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
- 125000004450 alkenylene group Chemical group 0.000 claims description 6
- 125000004429 atom Chemical group 0.000 claims description 6
- 239000000812 cholinergic antagonist Substances 0.000 claims description 6
- 150000003431 steroids Chemical class 0.000 claims description 6
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 239000000460 chlorine Substances 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 239000003149 muscarinic antagonist Substances 0.000 claims description 5
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 5
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical group OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
- 239000000825 pharmaceutical preparation Substances 0.000 claims description 4
- 229940127557 pharmaceutical product Drugs 0.000 claims description 4
- LKKKXVXXRSMKJD-UHFFFAOYSA-N 5-[2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-(methoxymethoxy)-6-methyl-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(OCOC)=CC(C)=C2C(O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 LKKKXVXXRSMKJD-UHFFFAOYSA-N 0.000 claims description 3
- 125000005529 alkyleneoxy group Chemical group 0.000 claims description 3
- 230000001022 anti-muscarinic effect Effects 0.000 claims description 3
- 125000000524 functional group Chemical group 0.000 claims description 3
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 3
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- OMOIDOQWHXDKBL-BQAIUKQQSA-N 4-[(1r)-2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-2-(dimethylamino)phenol;hydrochloride Chemical compound Cl.C1([C@@H](O)CNC2CC=3C=C(C(=CC=3C2)CC)CC)=CC=C(O)C(N(C)C)=C1 OMOIDOQWHXDKBL-BQAIUKQQSA-N 0.000 claims description 2
- AJAYTVZZTLZJFL-FTBISJDPSA-N 4-[(1r)-2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-2-(methylamino)phenol;hydrochloride Chemical compound Cl.C1([C@@H](O)CNC2CC=3C=C(C(=CC=3C2)CC)CC)=CC=C(O)C(NC)=C1 AJAYTVZZTLZJFL-FTBISJDPSA-N 0.000 claims description 2
- SXHDWOIPFGGJDK-QFIPXVFZSA-N 5-[(1r)-2-[(5,6-diethyl-2-methyl-1,3-dihydroinden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC1(C)CC(C=C(C(=C2)CC)CC)=C2C1 SXHDWOIPFGGJDK-QFIPXVFZSA-N 0.000 claims description 2
- AUUXBAOWHVOGFM-VZYDHVRKSA-N 5-[(1s)-2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one;hydrochloride Chemical compound Cl.N1C(=O)C=CC2=C1C(O)=CC=C2[C@H](O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 AUUXBAOWHVOGFM-VZYDHVRKSA-N 0.000 claims description 2
- HHEMVSCLLFFBQM-UHFFFAOYSA-N 5-[2-(2,3-dihydro-1h-inden-2-ylamino)-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2C(O)CNC1CC2=CC=CC=C2C1 HHEMVSCLLFFBQM-UHFFFAOYSA-N 0.000 claims description 2
- CEVVMMPBOCCERE-UHFFFAOYSA-N 5-[2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-3,4-dihydro-1h-quinolin-2-one Chemical compound N1C(=O)CCC2=C1C(O)=CC=C2C(O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 CEVVMMPBOCCERE-UHFFFAOYSA-N 0.000 claims description 2
- LNWINKMRDGCDER-UHFFFAOYSA-N 5-[2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-3-methyl-1h-quinolin-2-one Chemical compound N1C(=O)C(C)=CC2=C1C(O)=CC=C2C(O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 LNWINKMRDGCDER-UHFFFAOYSA-N 0.000 claims description 2
- IAYCRMOPCKGMOQ-UHFFFAOYSA-N 5-[2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-6-methyl-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC(C)=C2C(O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 IAYCRMOPCKGMOQ-UHFFFAOYSA-N 0.000 claims description 2
- ZQWNZUAMWNPQGR-UHFFFAOYSA-N 5-[2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]ethyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2CCNC1CC(C=C(C(=C2)CC)CC)=C2C1 ZQWNZUAMWNPQGR-UHFFFAOYSA-N 0.000 claims description 2
- XRZOULQZLDILQH-UHFFFAOYSA-N 5-[2-[(5,6-dimethoxy-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2C(O)CNC1CC(C=C(C(=C2)OC)OC)=C2C1 XRZOULQZLDILQH-UHFFFAOYSA-N 0.000 claims description 2
- IHAMMEZCFQUEDK-BDQAORGHSA-N 8-hydroxy-5-[(1r)-1-hydroxy-2-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-7-ylamino)ethyl]-1h-quinolin-2-one;hydrochloride Chemical compound Cl.C1CC2=CC=CC=C2CCC1NC[C@H](O)C1=CC=C(O)C2=C1C=CC(=O)N2 IHAMMEZCFQUEDK-BDQAORGHSA-N 0.000 claims description 2
- HKVADJQGWKQGFS-QFIPXVFZSA-N 8-hydroxy-5-[(1r)-1-hydroxy-2-[(2-methyl-1,3,5,6,7,8-hexahydrocyclopenta[b]naphthalen-2-yl)amino]ethyl]-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC1(C)CC2=CC(CCCC3)=C3C=C2C1 HKVADJQGWKQGFS-QFIPXVFZSA-N 0.000 claims description 2
- MXCGESVXTRYGMG-SFHVURJKSA-N 8-hydroxy-5-[(1r)-1-hydroxy-2-[(2-methyl-1,3-dihydroinden-2-yl)amino]ethyl]-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC1(C)CC2=CC=CC=C2C1 MXCGESVXTRYGMG-SFHVURJKSA-N 0.000 claims description 2
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 claims description 2
- 230000003213 activating effect Effects 0.000 claims description 2
- 125000005103 alkyl silyl group Chemical group 0.000 claims description 2
- AQYSYJUIMQTRMV-UHFFFAOYSA-N hypofluorous acid Chemical compound FO AQYSYJUIMQTRMV-UHFFFAOYSA-N 0.000 claims description 2
- QZZUEBNBZAPZLX-QFIPXVFZSA-N indacaterol Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 QZZUEBNBZAPZLX-QFIPXVFZSA-N 0.000 claims description 2
- 125000000468 ketone group Chemical group 0.000 claims description 2
- 229960001664 mometasone Drugs 0.000 claims description 2
- QLIIKPVHVRXHRI-CXSFZGCWSA-N mometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CCl)(O)[C@@]1(C)C[C@@H]2O QLIIKPVHVRXHRI-CXSFZGCWSA-N 0.000 claims description 2
- ODKRQDDMRJQBTD-FQEVSTJZSA-N n-[2-hydroxy-5-[(1r)-1-hydroxy-2-[(2,5,6-trimethyl-1,3-dihydroinden-2-yl)amino]ethyl]phenyl]formamide Chemical compound C1([C@@H](O)CNC2(C)CC=3C=C(C(=CC=3C2)C)C)=CC=C(O)C(NC=O)=C1 ODKRQDDMRJQBTD-FQEVSTJZSA-N 0.000 claims description 2
- OHCGKRMTTXXVKC-FQEVSTJZSA-N n-[2-hydroxy-5-[(1r)-1-hydroxy-2-[(2,5,6-trimethyl-1,3-dihydroinden-2-yl)amino]ethyl]phenyl]methanesulfonamide Chemical compound C1([C@@H](O)CNC2(C)CC=3C=C(C(=CC=3C2)C)C)=CC=C(O)C(NS(C)(=O)=O)=C1 OHCGKRMTTXXVKC-FQEVSTJZSA-N 0.000 claims description 2
- BZUWPMVYXALKSM-IBGZPJMESA-N n-[2-hydroxy-5-[(1r)-1-hydroxy-2-[(2-methyl-1,3-dihydroinden-2-yl)amino]ethyl]phenyl]ethanesulfonamide Chemical compound C1=C(O)C(NS(=O)(=O)CC)=CC([C@@H](O)CNC2(C)CC3=CC=CC=C3C2)=C1 BZUWPMVYXALKSM-IBGZPJMESA-N 0.000 claims description 2
- KKELHZCWVNOXPW-SFHVURJKSA-N n-[2-hydroxy-5-[(1r)-1-hydroxy-2-[(2-methyl-1,3-dihydroinden-2-yl)amino]ethyl]phenyl]methanesulfonamide Chemical compound C1([C@@H](O)CNC2(CC3=CC=CC=C3C2)C)=CC=C(O)C(NS(C)(=O)=O)=C1 KKELHZCWVNOXPW-SFHVURJKSA-N 0.000 claims description 2
- JYTUMKKJJYMWCL-FQEVSTJZSA-N n-[2-hydroxy-5-[(1r)-1-hydroxy-2-[(2-methyl-1,3-dihydroinden-2-yl)amino]ethyl]phenyl]propane-1-sulfonamide Chemical compound C1=C(O)C(NS(=O)(=O)CCC)=CC([C@@H](O)CNC2(C)CC3=CC=CC=C3C2)=C1 JYTUMKKJJYMWCL-FQEVSTJZSA-N 0.000 claims description 2
- MHHWPHGDSHBFAS-QFIPXVFZSA-N n-[5-[(1r)-2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-2-hydroxyphenyl]formamide Chemical compound C1([C@@H](O)CNC2CC=3C=C(C(=CC=3C2)CC)CC)=CC=C(O)C(NC=O)=C1 MHHWPHGDSHBFAS-QFIPXVFZSA-N 0.000 claims description 2
- SHZZLVKIWPKKBW-UHFFFAOYSA-N n-[5-[2-[(2-ethyl-1,3-dihydroinden-2-yl)amino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide Chemical compound C1C2=CC=CC=C2CC1(CC)NCC(O)C1=CC=C(O)C(NS(C)(=O)=O)=C1 SHZZLVKIWPKKBW-UHFFFAOYSA-N 0.000 claims description 2
- WWPJIPRDNLFUBN-UHFFFAOYSA-N n-[5-[2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-2-hydroxyphenyl]methanesulfonamide;hydrochloride Chemical compound Cl.C1C=2C=C(CC)C(CC)=CC=2CC1NCC(O)C1=CC=C(O)C(NS(C)(=O)=O)=C1 WWPJIPRDNLFUBN-UHFFFAOYSA-N 0.000 claims description 2
- 230000037361 pathway Effects 0.000 claims description 2
- 230000000241 respiratory effect Effects 0.000 claims description 2
- 230000001078 anti-cholinergic effect Effects 0.000 claims 3
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims 2
- AUUXBAOWHVOGFM-FTBISJDPSA-N 5-[(1r)-2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one;hydrochloride Chemical compound Cl.N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 AUUXBAOWHVOGFM-FTBISJDPSA-N 0.000 claims 1
- 150000001649 bromium compounds Chemical group 0.000 claims 1
- 229960003638 dopamine Drugs 0.000 claims 1
- IREJFXIHXRZFER-PCBAQXHCSA-N indacaterol maleate Chemical compound OC(=O)\C=C/C(O)=O.N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 IREJFXIHXRZFER-PCBAQXHCSA-N 0.000 claims 1
- 239000000018 receptor agonist Substances 0.000 claims 1
- 229940044601 receptor agonist Drugs 0.000 claims 1
- LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical compound O([C@H]1C[C@@H]2[N+]([C@H](C1)[C@@H]1[C@H]2O1)(C)C)C(=O)C(O)(C=1SC=CC=1)C1=CC=CS1 LERNTVKEWCAPOY-DZZGSBJMSA-N 0.000 claims 1
- 229940110309 tiotropium Drugs 0.000 claims 1
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 abstract description 10
- 125000005843 halogen group Chemical group 0.000 abstract description 4
- 125000004665 trialkylsilyl group Chemical group 0.000 abstract description 2
- 125000001054 5 membered carbocyclic group Chemical group 0.000 abstract 1
- 125000004008 6 membered carbocyclic group Chemical group 0.000 abstract 1
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 189
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 144
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 130
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 89
- 239000000047 product Substances 0.000 description 73
- 239000000377 silicon dioxide Substances 0.000 description 66
- 239000000543 intermediate Substances 0.000 description 57
- 239000002904 solvent Substances 0.000 description 56
- 238000004809 thin layer chromatography Methods 0.000 description 55
- 238000005160 1H NMR spectroscopy Methods 0.000 description 47
- 238000006243 chemical reaction Methods 0.000 description 43
- 239000000243 solution Substances 0.000 description 43
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 36
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 35
- 239000011541 reaction mixture Substances 0.000 description 34
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 33
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 25
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 21
- 238000003818 flash chromatography Methods 0.000 description 18
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 18
- 235000019341 magnesium sulphate Nutrition 0.000 description 18
- 238000005481 NMR spectroscopy Methods 0.000 description 16
- 239000003795 chemical substances by application Substances 0.000 description 16
- 238000004587 chromatography analysis Methods 0.000 description 16
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 14
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 14
- 239000003054 catalyst Substances 0.000 description 14
- 208000006673 asthma Diseases 0.000 description 13
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 12
- 239000012298 atmosphere Substances 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 11
- 150000002148 esters Chemical class 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 10
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 229910052763 palladium Inorganic materials 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 239000011780 sodium chloride Substances 0.000 description 9
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 230000003197 catalytic effect Effects 0.000 description 8
- 239000000706 filtrate Substances 0.000 description 8
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 7
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
- 229940124630 bronchodilator Drugs 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 230000009471 action Effects 0.000 description 6
- 125000003342 alkenyl group Chemical group 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 6
- 238000001914 filtration Methods 0.000 description 6
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 6
- 239000003921 oil Substances 0.000 description 6
- 235000019198 oils Nutrition 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 208000023504 respiratory system disease Diseases 0.000 description 6
- 229920006395 saturated elastomer Polymers 0.000 description 6
- 239000000741 silica gel Substances 0.000 description 6
- 229910002027 silica gel Inorganic materials 0.000 description 6
- KGVIJLMNQNSQHB-UHFFFAOYSA-N 5,6-diethyl-2,3-dihydro-1h-inden-2-amine Chemical compound C1=C(CC)C(CC)=CC2=C1CC(N)C2 KGVIJLMNQNSQHB-UHFFFAOYSA-N 0.000 description 5
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-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
- 229940124748 beta 2 agonist Drugs 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 229910000069 nitrogen hydride Inorganic materials 0.000 description 5
- 239000012279 sodium borohydride Substances 0.000 description 5
- 229910000033 sodium borohydride Inorganic materials 0.000 description 5
- 229910052938 sodium sulfate Inorganic materials 0.000 description 5
- 235000011152 sodium sulphate Nutrition 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 4
- 102100039705 Beta-2 adrenergic receptor Human genes 0.000 description 4
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- 239000008346 aqueous phase Substances 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
- 239000000168 bronchodilator agent Substances 0.000 description 4
- 230000001684 chronic effect Effects 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 239000000284 extract Substances 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 238000005984 hydrogenation reaction Methods 0.000 description 4
- 239000012280 lithium aluminium hydride Substances 0.000 description 4
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000002560 therapeutic procedure Methods 0.000 description 4
- ILYNGEKWZMAGTC-UHFFFAOYSA-N 2-ethyl-1,3-dihydroinden-2-amine Chemical compound C1=CC=C2CC(CC)(N)CC2=C1 ILYNGEKWZMAGTC-UHFFFAOYSA-N 0.000 description 3
- KCSSOJNWNVBDET-UHFFFAOYSA-N 2-hydroxyimino-4,5,6,7-tetramethyl-3h-inden-1-one Chemical compound CC1=C(C)C(C)=C2CC(=NO)C(=O)C2=C1C KCSSOJNWNVBDET-UHFFFAOYSA-N 0.000 description 3
- NGMAFKIQHCGAJV-UHFFFAOYSA-N 2-methyl-1,2,5,6,7,8-hexahydrocyclopenta[b]naphthalen-3-one Chemical compound C1CCCC2=C1C=C1CC(C)C(=O)C1=C2 NGMAFKIQHCGAJV-UHFFFAOYSA-N 0.000 description 3
- NWLUVPKKKNCNIW-UHFFFAOYSA-N 2-methyl-1,3-dihydroinden-2-amine Chemical compound C1=CC=C2CC(C)(N)CC2=C1 NWLUVPKKKNCNIW-UHFFFAOYSA-N 0.000 description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 3
- OTINTMLHLKCOBW-MUUNZHRXSA-N 5-[(1s)-2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C1=2NC(=O)C=CC=2C([C@H](O)CNC2CC=3C=C(C(=CC=3C2)CC)CC)=CC=C1OCC1=CC=CC=C1 OTINTMLHLKCOBW-MUUNZHRXSA-N 0.000 description 3
- QZZUEBNBZAPZLX-UHFFFAOYSA-N 5-[2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2C(O)CNC1CC(C=C(C(=C2)CC)CC)=C2C1 QZZUEBNBZAPZLX-UHFFFAOYSA-N 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- 239000012359 Methanesulfonyl chloride Substances 0.000 description 3
- 229910019020 PtO2 Inorganic materials 0.000 description 3
- 230000001154 acute effect Effects 0.000 description 3
- YKIOKAURTKXMSB-UHFFFAOYSA-N adams's catalyst Chemical compound O=[Pt]=O YKIOKAURTKXMSB-UHFFFAOYSA-N 0.000 description 3
- 102000014992 beta1-adrenergic receptor activity proteins Human genes 0.000 description 3
- 108040006808 beta1-adrenergic receptor activity proteins Proteins 0.000 description 3
- 206010006451 bronchitis Diseases 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- UEXQBEVWFZKHNB-UHFFFAOYSA-N intermediate 29 Natural products C1=CC(N)=CC=C1NC1=NC=CC=N1 UEXQBEVWFZKHNB-UHFFFAOYSA-N 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 3
- IHOSBCLPHULSMP-UHFFFAOYSA-N n-(5-ethyl-2-methyl-1,3-dihydroinden-2-yl)benzamide Chemical compound C1C2=CC(CC)=CC=C2CC1(C)NC(=O)C1=CC=CC=C1 IHOSBCLPHULSMP-UHFFFAOYSA-N 0.000 description 3
- LHFWNCMXGVHLQX-UHFFFAOYSA-N n-benzyl-5,6-diethyl-2,3-dihydro-1h-inden-2-amine Chemical compound C1C=2C=C(CC)C(CC)=CC=2CC1NCC1=CC=CC=C1 LHFWNCMXGVHLQX-UHFFFAOYSA-N 0.000 description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 3
- QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 3
- RZWZRACFZGVKFM-UHFFFAOYSA-N propanoyl chloride Chemical compound CCC(Cl)=O RZWZRACFZGVKFM-UHFFFAOYSA-N 0.000 description 3
- 230000009467 reduction Effects 0.000 description 3
- 210000002345 respiratory system Anatomy 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000004448 titration Methods 0.000 description 3
- FHCUYBPYZQCJJS-UMSFTDKQSA-N (1r)-1-(3-amino-4-phenylmethoxyphenyl)-2-[benzyl-(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]ethanol Chemical compound NC1=CC([C@@H](O)CN(C2CC=3C=C(C(=CC=3C2)CC)CC)CC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 FHCUYBPYZQCJJS-UMSFTDKQSA-N 0.000 description 2
- VHUSIVDRJQHDDT-YTTGMZPUSA-N (1r)-2-[benzyl-(2,5,6-trimethyl-1,3-dihydroinden-2-yl)amino]-1-(3-nitro-4-phenylmethoxyphenyl)ethanol Chemical compound [O-][N+](=O)C1=CC([C@@H](O)CN(C2(C)CC=3C=C(C(=CC=3C2)C)C)CC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 VHUSIVDRJQHDDT-YTTGMZPUSA-N 0.000 description 2
- KVNYFPKFSJIPBJ-UHFFFAOYSA-N 1,2-diethylbenzene Chemical compound CCC1=CC=CC=C1CC KVNYFPKFSJIPBJ-UHFFFAOYSA-N 0.000 description 2
- WXAPHLBKQULQIY-UHFFFAOYSA-N 2,2,2-trifluoro-n-(2-methyl-1,3-dihydroinden-2-yl)acetamide Chemical compound C1=CC=C2CC(C)(NC(=O)C(F)(F)F)CC2=C1 WXAPHLBKQULQIY-UHFFFAOYSA-N 0.000 description 2
- ZZWFHZOSFDLLMU-UHFFFAOYSA-N 2,5,6-trimethyl-1,3-dihydroinden-2-amine Chemical compound C1=C(C)C(C)=CC2=C1CC(C)(N)C2 ZZWFHZOSFDLLMU-UHFFFAOYSA-N 0.000 description 2
- GIUDGQPFOOPWIQ-UHFFFAOYSA-N 2-ethyl-2,3-dihydroinden-1-one Chemical compound C1=CC=C2C(=O)C(CC)CC2=C1 GIUDGQPFOOPWIQ-UHFFFAOYSA-N 0.000 description 2
- AORHMRMTJLVENO-UHFFFAOYSA-N 2-methyl-1,3,5,6,7,8-hexahydrocyclopenta[b]naphthalen-2-amine Chemical compound C1CCCC2=C1C=C1CC(C)(N)CC1=C2 AORHMRMTJLVENO-UHFFFAOYSA-N 0.000 description 2
- GODHBZSNKYNBID-UHFFFAOYSA-N 3-Methyl-quinolin-2,8-diol Chemical compound C1=CC(O)=C2NC(=O)C(C)=CC2=C1 GODHBZSNKYNBID-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
- GUBTVZSSQXNMRG-UHFFFAOYSA-N 3-chloro-1-(2,3,4,5-tetramethylphenyl)propan-1-one Chemical compound CC1=CC(C(=O)CCCl)=C(C)C(C)=C1C GUBTVZSSQXNMRG-UHFFFAOYSA-N 0.000 description 2
- YDVVCNQRKYGFEJ-UHFFFAOYSA-N 3-chloro-1-(3,4-diethylphenyl)propan-1-one Chemical compound CCC1=CC=C(C(=O)CCCl)C=C1CC YDVVCNQRKYGFEJ-UHFFFAOYSA-N 0.000 description 2
- XJOBHVIAIFOKSI-UHFFFAOYSA-N 3-methyl-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C=12NC(=O)C(C)=CC2=CC=CC=1OCC1=CC=CC=C1 XJOBHVIAIFOKSI-UHFFFAOYSA-N 0.000 description 2
- OSPFVPPFODDSDS-UHFFFAOYSA-N 4,5,6,7-tetramethyl-2,3-dihydroinden-1-one Chemical compound CC1=C(C)C(C)=C2CCC(=O)C2=C1C OSPFVPPFODDSDS-UHFFFAOYSA-N 0.000 description 2
- IBNBOWHDRVHHRZ-UHFFFAOYSA-N 5,6-diethyl-2,3-dihydroinden-1-one Chemical compound C1=C(CC)C(CC)=CC2=C1C(=O)CC2 IBNBOWHDRVHHRZ-UHFFFAOYSA-N 0.000 description 2
- UQGBLGLYOTZUIW-UHFFFAOYSA-N 5,6-diethyl-2-methyl-1,3-dihydroinden-2-amine Chemical compound C1=C(CC)C(CC)=CC2=C1CC(C)(N)C2 UQGBLGLYOTZUIW-UHFFFAOYSA-N 0.000 description 2
- QVDNUYMHJUKMDL-DEOSSOPVSA-N 5-[(1r)-2-[(4,7-dimethoxy-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C1=2NC(=O)C=CC=2C([C@@H](O)CNC2CC=3C(OC)=CC=C(C=3C2)OC)=CC=C1OCC1=CC=CC=C1 QVDNUYMHJUKMDL-DEOSSOPVSA-N 0.000 description 2
- ZKCIIJWVIAWIJD-OAHLLOKOSA-N 5-[(1s)-2-chloro-1-hydroxyethyl]-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C1=2NC(=O)C=CC=2C([C@@H](CCl)O)=CC=C1OCC1=CC=CC=C1 ZKCIIJWVIAWIJD-OAHLLOKOSA-N 0.000 description 2
- BRXWLXNLRQLPTD-UHFFFAOYSA-N 5-bromo-8-(methoxymethoxy)-6-methyl-1h-quinolin-2-one Chemical compound C1=CC(=O)NC2=C1C(Br)=C(C)C=C2OCOC BRXWLXNLRQLPTD-UHFFFAOYSA-N 0.000 description 2
- JDNXBENMVHMNPU-UHFFFAOYSA-N 5-bromo-8-hydroxy-6-methyl-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C(Br)C(C)=CC(O)=C21 JDNXBENMVHMNPU-UHFFFAOYSA-N 0.000 description 2
- WTTMMQYRGFRBCF-UHFFFAOYSA-N 5-ethenyl-3-methyl-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C=12NC(=O)C(C)=CC2=C(C=C)C=CC=1OCC1=CC=CC=C1 WTTMMQYRGFRBCF-UHFFFAOYSA-N 0.000 description 2
- GIUGLIISNBOAIB-UHFFFAOYSA-N 8-hydroxy-6-methyl-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=CC(C)=CC(O)=C21 GIUGLIISNBOAIB-UHFFFAOYSA-N 0.000 description 2
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 description 2
- 101710152983 Beta-2 adrenergic receptor Proteins 0.000 description 2
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 2
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 2
- 241000700199 Cavia porcellus Species 0.000 description 2
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 2
- KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 description 2
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 2
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 2
- 201000004681 Psoriasis Diseases 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- UCTWMZQNUQWSLP-UHFFFAOYSA-N adrenaline Chemical compound CNCC(O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-UHFFFAOYSA-N 0.000 description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
- 229910021529 ammonia Inorganic materials 0.000 description 2
- 239000002260 anti-inflammatory agent Substances 0.000 description 2
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 2
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 2
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 description 2
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000002775 capsule Substances 0.000 description 2
- 150000001721 carbon Chemical group 0.000 description 2
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 2
- 238000007796 conventional method Methods 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 238000007865 diluting Methods 0.000 description 2
- 239000003085 diluting agent Substances 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003136 dopamine receptor stimulating agent Substances 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 229910052731 fluorine Inorganic materials 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 239000000499 gel Substances 0.000 description 2
- VKYKSIONXSXAKP-UHFFFAOYSA-N hexamethylenetetramine Chemical compound C1N(C2)CN3CN1CN2C3 VKYKSIONXSXAKP-UHFFFAOYSA-N 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- PQNFLJBBNBOBRQ-UHFFFAOYSA-N indane Chemical compound C1=CC=C2CCCC2=C1 PQNFLJBBNBOBRQ-UHFFFAOYSA-N 0.000 description 2
- 239000012442 inert solvent Substances 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 239000011976 maleic acid Substances 0.000 description 2
- KYPVJWLAFKKRBG-UHFFFAOYSA-N n-(1-hydroxy-4,5,6,7-tetramethyl-2,3-dihydro-1h-inden-2-yl)benzamide Chemical compound OC1C2=C(C)C(C)=C(C)C(C)=C2CC1NC(=O)C1=CC=CC=C1 KYPVJWLAFKKRBG-UHFFFAOYSA-N 0.000 description 2
- KOOYARCZGQNZCL-UHFFFAOYSA-N n-(4,5,6,7-tetramethyl-2,3-dihydro-1h-inden-2-yl)benzamide Chemical compound C1C2=C(C)C(C)=C(C)C(C)=C2CC1NC(=O)C1=CC=CC=C1 KOOYARCZGQNZCL-UHFFFAOYSA-N 0.000 description 2
- QZKBDSDCHUVKHI-UHFFFAOYSA-N n-(4,5,6,7-tetramethyl-3-oxo-1,2-dihydroinden-2-yl)benzamide Chemical compound O=C1C2=C(C)C(C)=C(C)C(C)=C2CC1NC(=O)C1=CC=CC=C1 QZKBDSDCHUVKHI-UHFFFAOYSA-N 0.000 description 2
- JPYJMSWFVSYGRC-UHFFFAOYSA-N n-(5,6-diethyl-2-methyl-1,3-dihydroinden-2-yl)benzamide Chemical compound C1C=2C=C(CC)C(CC)=CC=2CC1(C)NC(=O)C1=CC=CC=C1 JPYJMSWFVSYGRC-UHFFFAOYSA-N 0.000 description 2
- OPSOYAZKNLIEDC-UHFFFAOYSA-N n-(5-acetyl-2-methyl-1,3-dihydroinden-2-yl)benzamide Chemical compound C1C2=CC(C(=O)C)=CC=C2CC1(C)NC(=O)C1=CC=CC=C1 OPSOYAZKNLIEDC-UHFFFAOYSA-N 0.000 description 2
- WJEWWXVHHRPBLJ-UHFFFAOYSA-N n-(5-acetyl-6-ethyl-2-methyl-1,3-dihydroinden-2-yl)benzamide Chemical compound C1C=2C=C(C(C)=O)C(CC)=CC=2CC1(C)NC(=O)C1=CC=CC=C1 WJEWWXVHHRPBLJ-UHFFFAOYSA-N 0.000 description 2
- IXSQDOHUJYJMHR-UHFFFAOYSA-N n-[5,6-bis(methoxymethyl)-2,3-dihydro-1h-inden-2-yl]-2,2,2-trifluoroacetamide Chemical compound C1=C(COC)C(COC)=CC2=C1CC(NC(=O)C(F)(F)F)C2 IXSQDOHUJYJMHR-UHFFFAOYSA-N 0.000 description 2
- YOYWEMSVVGDJCZ-UHFFFAOYSA-N n-benzyl-2,3,5,6,7,8-hexahydro-1h-cyclopenta[b]naphthalen-2-amine Chemical compound C1C2=CC=3CCCCC=3C=C2CC1NCC1=CC=CC=C1 YOYWEMSVVGDJCZ-UHFFFAOYSA-N 0.000 description 2
- VWIPJTRMRARDRI-UHFFFAOYSA-N n-benzyl-2,5,6-trimethyl-1,3-dihydroinden-2-amine Chemical compound C1C=2C=C(C)C(C)=CC=2CC1(C)NCC1=CC=CC=C1 VWIPJTRMRARDRI-UHFFFAOYSA-N 0.000 description 2
- IKJPMBLNTXLPLH-UHFFFAOYSA-N n-benzyl-4,5,6,7-tetramethyl-2,3-dihydro-1h-inden-2-amine Chemical compound C1C2=C(C)C(C)=C(C)C(C)=C2CC1NCC1=CC=CC=C1 IKJPMBLNTXLPLH-UHFFFAOYSA-N 0.000 description 2
- WENRYBMPSMOVFX-UHFFFAOYSA-N n-benzyl-5,6-diethyl-2-methyl-1,3-dihydroinden-2-amine Chemical compound C1C=2C=C(CC)C(CC)=CC=2CC1(C)NCC1=CC=CC=C1 WENRYBMPSMOVFX-UHFFFAOYSA-N 0.000 description 2
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001624 naphthyl group Chemical group 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 206010035653 pneumoconiosis Diseases 0.000 description 2
- CHKVPAROMQMJNQ-UHFFFAOYSA-M potassium bisulfate Chemical compound [K+].OS([O-])(=O)=O CHKVPAROMQMJNQ-UHFFFAOYSA-M 0.000 description 2
- 229910000343 potassium bisulfate Inorganic materials 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- UOHMMEJUHBCKEE-UHFFFAOYSA-N prehnitene Chemical compound CC1=CC=C(C)C(C)=C1C UOHMMEJUHBCKEE-UHFFFAOYSA-N 0.000 description 2
- 238000002953 preparative HPLC Methods 0.000 description 2
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 2
- 230000000069 prophylactic effect Effects 0.000 description 2
- 238000011321 prophylaxis Methods 0.000 description 2
- 125000006239 protecting group Chemical group 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- QBERHIJABFXGRZ-UHFFFAOYSA-M rhodium;triphenylphosphane;chloride Chemical compound [Cl-].[Rh].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QBERHIJABFXGRZ-UHFFFAOYSA-M 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 235000017557 sodium bicarbonate Nutrition 0.000 description 2
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 230000001975 sympathomimetic effect Effects 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 230000001225 therapeutic effect Effects 0.000 description 2
- 210000003437 trachea Anatomy 0.000 description 2
- QIWRFOJWQSSRJZ-UHFFFAOYSA-N tributyl(ethenyl)stannane Chemical compound CCCC[Sn](CCCC)(CCCC)C=C QIWRFOJWQSSRJZ-UHFFFAOYSA-N 0.000 description 2
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- UMIFTFDEUAACGZ-PMERELPUSA-N (1r)-2-[benzyl-(2-methyl-1,3-dihydroinden-2-yl)amino]-1-(3-nitro-4-phenylmethoxyphenyl)ethanol Chemical compound [O-][N+](=O)C1=CC([C@@H](O)CN(C2(CC3=CC=CC=C3C2)C)CC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 UMIFTFDEUAACGZ-PMERELPUSA-N 0.000 description 1
- SJIRFKNRYHFJNS-UMSFTDKQSA-N (1r)-2-[benzyl-(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-(3-nitro-4-phenylmethoxyphenyl)ethanol Chemical compound [O-][N+](=O)C1=CC([C@@H](O)CN(C2CC=3C=C(C(=CC=3C2)CC)CC)CC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 SJIRFKNRYHFJNS-UMSFTDKQSA-N 0.000 description 1
- BMOPWVHPMDAKLB-BHVANESWSA-N (1r)-2-[benzyl-(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-[3-(dimethylamino)-4-phenylmethoxyphenyl]ethanol Chemical compound CN(C)C1=CC([C@@H](O)CN(C2CC=3C=C(C(=CC=3C2)CC)CC)CC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 BMOPWVHPMDAKLB-BHVANESWSA-N 0.000 description 1
- RNGKBBJEPDBEPA-DHUJRADRSA-N (1r)-2-[benzyl-(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-[3-(methylamino)-4-phenylmethoxyphenyl]ethanol Chemical compound CNC1=CC([C@@H](O)CN(C2CC=3C=C(C(=CC=3C2)CC)CC)CC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 RNGKBBJEPDBEPA-DHUJRADRSA-N 0.000 description 1
- JFXCOBFYHVECCA-PMERELPUSA-N (3R)-4-[benzyl-(2-methyl-1,3-dihydroinden-2-yl)amino]-3-(3-nitro-4-phenylmethoxyphenyl)butanoic acid Chemical compound C(C1=CC=CC=C1)N(C[C@@H](C1=CC(=C(C=C1)OCC1=CC=CC=C1)[N+](=O)[O-])CC(=O)O)C1(CC2=CC=CC=C2C1)C JFXCOBFYHVECCA-PMERELPUSA-N 0.000 description 1
- VMKAFJQFKBASMU-KRWDZBQOSA-N (3as)-1-methyl-3,3-diphenyl-3a,4,5,6-tetrahydropyrrolo[1,2-c][1,3,2]oxazaborole Chemical compound C([C@H]12)CCN1B(C)OC2(C=1C=CC=CC=1)C1=CC=CC=C1 VMKAFJQFKBASMU-KRWDZBQOSA-N 0.000 description 1
- BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 description 1
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- YFUQYYGBJJCAPR-UHFFFAOYSA-N 1,4-dimethoxybut-2-yne Chemical compound COCC#CCOC YFUQYYGBJJCAPR-UHFFFAOYSA-N 0.000 description 1
- UCZYEVXBDMTOGJ-UHFFFAOYSA-N 1-(3-amino-4-phenylmethoxyphenyl)-2-[benzyl-(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]ethanone Chemical compound C1C=2C=C(CC)C(CC)=CC=2CC1N(CC=1C=CC=CC=1)CC(=O)C(C=C1N)=CC=C1OCC1=CC=CC=C1 UCZYEVXBDMTOGJ-UHFFFAOYSA-N 0.000 description 1
- PHNDNMUNLFAVNR-UHFFFAOYSA-N 1-(5,6,7,8-tetrahydronaphthalen-2-yl)propan-1-one Chemical compound C1CCCC2=CC(C(=O)CC)=CC=C21 PHNDNMUNLFAVNR-UHFFFAOYSA-N 0.000 description 1
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 1
- AFFLGGQVNFXPEV-UHFFFAOYSA-N 1-decene Chemical group CCCCCCCCC=C AFFLGGQVNFXPEV-UHFFFAOYSA-N 0.000 description 1
- 125000006017 1-propenyl group Chemical group 0.000 description 1
- TZZBVFJJRUDHNH-UHFFFAOYSA-N 2,2,2-trifluoro-n-(2-methyl-3-oxo-1h-inden-2-yl)acetamide Chemical compound C1=CC=C2C(=O)C(C)(NC(=O)C(F)(F)F)CC2=C1 TZZBVFJJRUDHNH-UHFFFAOYSA-N 0.000 description 1
- FQUBLOGPLMBSOR-UHFFFAOYSA-N 2,2,2-trifluoro-n-(2-methyl-3-oxo-5,6,7,8-tetrahydro-1h-cyclopenta[b]naphthalen-2-yl)acetamide Chemical compound C1CCCC2=C1C=C1CC(NC(=O)C(F)(F)F)(C)C(=O)C1=C2 FQUBLOGPLMBSOR-UHFFFAOYSA-N 0.000 description 1
- RVZHKBONUJADKD-UHFFFAOYSA-N 2,2,2-trifluoro-n-hepta-1,6-diyn-4-ylacetamide Chemical compound FC(F)(F)C(=O)NC(CC#C)CC#C RVZHKBONUJADKD-UHFFFAOYSA-N 0.000 description 1
- SZSIVGMKIWMNMQ-UHFFFAOYSA-N 2,3,5,6,7,8-hexahydro-1h-cyclopenta[b]naphthalen-2-amine Chemical compound C1CCCC2=C1C=C1CC(N)CC1=C2 SZSIVGMKIWMNMQ-UHFFFAOYSA-N 0.000 description 1
- OOUDESMQRSSPGN-UHFFFAOYSA-N 2-[benzyl-(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-(3-nitro-4-phenylmethoxyphenyl)ethanone Chemical compound C1C=2C=C(CC)C(CC)=CC=2CC1N(CC=1C=CC=CC=1)CC(=O)C(C=C1[N+]([O-])=O)=CC=C1OCC1=CC=CC=C1 OOUDESMQRSSPGN-UHFFFAOYSA-N 0.000 description 1
- HTWHLAQQUBJQLF-UHFFFAOYSA-N 2-amino-2-methyl-3h-inden-1-one Chemical compound C1=CC=C2C(=O)C(C)(N)CC2=C1 HTWHLAQQUBJQLF-UHFFFAOYSA-N 0.000 description 1
- XEZVRSFMYPORQH-UHFFFAOYSA-N 2-amino-4,5,6,7-tetramethyl-2,3-dihydroinden-1-one;hydrochloride Chemical compound Cl.CC1=C(C)C(C)=C2CC(N)C(=O)C2=C1C XEZVRSFMYPORQH-UHFFFAOYSA-N 0.000 description 1
- LMHHFZAXSANGGM-UHFFFAOYSA-N 2-aminoindane Chemical compound C1=CC=C2CC(N)CC2=C1 LMHHFZAXSANGGM-UHFFFAOYSA-N 0.000 description 1
- PBAAKBQGBSUCTG-UHFFFAOYSA-N 2-bromo-1-(3-nitro-4-phenylmethoxyphenyl)ethanone Chemical compound [O-][N+](=O)C1=CC(C(=O)CBr)=CC=C1OCC1=CC=CC=C1 PBAAKBQGBSUCTG-UHFFFAOYSA-N 0.000 description 1
- WBJWXIQDBDZMAW-UHFFFAOYSA-N 2-hydroxynaphthalene-1-carbonyl chloride Chemical compound C1=CC=CC2=C(C(Cl)=O)C(O)=CC=C21 WBJWXIQDBDZMAW-UHFFFAOYSA-N 0.000 description 1
- BEKNOGMQVKBMQN-UHFFFAOYSA-N 2-methyl-2,3-dihydroinden-1-one Chemical compound C1=CC=C2C(=O)C(C)CC2=C1 BEKNOGMQVKBMQN-UHFFFAOYSA-N 0.000 description 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 description 1
- ALKYHXVLJMQRLQ-UHFFFAOYSA-N 3-Hydroxy-2-naphthoate Chemical compound C1=CC=C2C=C(O)C(C(=O)O)=CC2=C1 ALKYHXVLJMQRLQ-UHFFFAOYSA-N 0.000 description 1
- NHHCOVSYOYGSNY-UHFFFAOYSA-N 3h-naphthalen-2-one Chemical compound C1=CC=CC2=CC(=O)CC=C21 NHHCOVSYOYGSNY-UHFFFAOYSA-N 0.000 description 1
- MOUCINMECNAGTR-UHFFFAOYSA-N 4,7-dimethoxy-2,3-dihydro-1h-inden-2-amine Chemical compound COC1=CC=C(OC)C2=C1CC(N)C2 MOUCINMECNAGTR-UHFFFAOYSA-N 0.000 description 1
- MRLBDJHIJZHYMK-UHFFFAOYSA-N 5,6,8,9-tetrahydrobenzo[7]annulen-7-one Chemical compound C1CC(=O)CCC2=CC=CC=C21 MRLBDJHIJZHYMK-UHFFFAOYSA-N 0.000 description 1
- IGKJHEPOSYGFBE-UHFFFAOYSA-N 5,6-diethyl-1h-inden-2-amine;hydrochloride Chemical compound Cl.C1=C(CC)C(CC)=CC2=C1C=C(N)C2 IGKJHEPOSYGFBE-UHFFFAOYSA-N 0.000 description 1
- ZOVIYWYFBOQKIA-UHFFFAOYSA-N 5,6-diethyl-2,3-dihydro-1h-inden-2-amine;hydrochloride Chemical compound Cl.C1=C(CC)C(CC)=CC2=C1CC(N)C2 ZOVIYWYFBOQKIA-UHFFFAOYSA-N 0.000 description 1
- ZXYHUDMEPGYCDF-UHFFFAOYSA-N 5-(2-chloroacetyl)-8-hydroxy-1h-quinolin-2-one Chemical compound C1=CC(=O)NC2=C1C(C(=O)CCl)=CC=C2O ZXYHUDMEPGYCDF-UHFFFAOYSA-N 0.000 description 1
- AUFKEUKWVZCLQD-UHFFFAOYSA-N 5-(2-chloroacetyl)-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C1=2NC(=O)C=CC=2C(C(=O)CCl)=CC=C1OCC1=CC=CC=C1 AUFKEUKWVZCLQD-UHFFFAOYSA-N 0.000 description 1
- RINMWWBXDYZEGN-SANMLTNESA-N 5-[(1r)-1-hydroxy-2-(6,7,8,9-tetrahydro-5h-benzo[7]annulen-7-ylamino)ethyl]-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C1=2NC(=O)C=CC=2C([C@H](CNC2CCC3=CC=CC=C3CC2)O)=CC=C1OCC1=CC=CC=C1 RINMWWBXDYZEGN-SANMLTNESA-N 0.000 description 1
- NIEPRCWEGNACAG-NDEPHWFRSA-N 5-[(1r)-1-hydroxy-2-[(2-methyl-1,3,5,6,7,8-hexahydrocyclopenta[b]naphthalen-2-yl)amino]ethyl]-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C1=2NC(=O)C=CC=2C([C@@H](O)CNC2(CC3=CC=4CCCCC=4C=C3C2)C)=CC=C1OCC1=CC=CC=C1 NIEPRCWEGNACAG-NDEPHWFRSA-N 0.000 description 1
- YCSCMFCLTYHCHM-DEOSSOPVSA-N 5-[(1r)-1-hydroxy-2-[(2-methyl-1,3-dihydroinden-2-yl)amino]ethyl]-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C1=2NC(=O)C=CC=2C([C@@H](O)CNC2(CC3=CC=CC=C3C2)C)=CC=C1OCC1=CC=CC=C1 YCSCMFCLTYHCHM-DEOSSOPVSA-N 0.000 description 1
- YDASIKMMYCNIMH-FERBBOLQSA-N 5-[(1r)-2-[(4,7-dimethoxy-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one;hydrochloride Chemical compound Cl.N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC1CC(C(OC)=CC=C2OC)=C2C1 YDASIKMMYCNIMH-FERBBOLQSA-N 0.000 description 1
- OTINTMLHLKCOBW-NDEPHWFRSA-N 5-[(1r)-2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C1=2NC(=O)C=CC=2C([C@@H](O)CNC2CC=3C=C(C(=CC=3C2)CC)CC)=CC=C1OCC1=CC=CC=C1 OTINTMLHLKCOBW-NDEPHWFRSA-N 0.000 description 1
- QCELPGAGLMHLEZ-PGUFJCEWSA-N 5-[(1s)-2-[benzyl(2,3,5,6,7,8-hexahydro-1h-cyclopenta[b]naphthalen-2-yl)amino]-1-hydroxyethyl]-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C([C@@H](O)C=1C=2C=CC(=O)NC=2C(OCC=2C=CC=CC=2)=CC=1)N(C1CC2=CC=3CCCCC=3C=C2C1)CC1=CC=CC=C1 QCELPGAGLMHLEZ-PGUFJCEWSA-N 0.000 description 1
- OYYLOIYUSXZWRO-UHFFFAOYSA-N 5-[1-hydroxy-2-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)amino]ethyl]-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C1C2=CC(OC)=CC=C2CCC1NCC(O)C(C=1C=CC(=O)NC=11)=CC=C1OCC1=CC=CC=C1 OYYLOIYUSXZWRO-UHFFFAOYSA-N 0.000 description 1
- HBNDLGUTEBJNAA-UHFFFAOYSA-N 5-[2-(2,3-dihydro-1h-inden-2-ylamino)acetyl]-8-hydroxy-1h-quinolin-2-one Chemical compound C1=CC(=O)NC2=C1C(C(=O)CNC1CC3=CC=CC=C3C1)=CC=C2O HBNDLGUTEBJNAA-UHFFFAOYSA-N 0.000 description 1
- UBAONYWGJPHIFN-UHFFFAOYSA-N 5-[2-[(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-3-methyl-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C1C=2C=C(CC)C(CC)=CC=2CC1NCC(O)C(C=1C=C(C)C(=O)NC=11)=CC=C1OCC1=CC=CC=C1 UBAONYWGJPHIFN-UHFFFAOYSA-N 0.000 description 1
- BFLYKPHONQLTTE-UHFFFAOYSA-N 5-ethenyl-8-(methoxymethoxy)-6-methyl-1h-quinolin-2-one Chemical compound C1=CC(=O)NC2=C1C(C=C)=C(C)C=C2OCOC BFLYKPHONQLTTE-UHFFFAOYSA-N 0.000 description 1
- BGKVEHAWZXNHBI-UHFFFAOYSA-N 6,7,8,9-tetrahydro-5h-benzo[7]annulen-7-amine Chemical compound C1CC(N)CCC2=CC=CC=C21 BGKVEHAWZXNHBI-UHFFFAOYSA-N 0.000 description 1
- AHPFGQFVXABBSZ-LJAQVGFWSA-N 8-(benzylamino)-5-[(1r)-2-[(5,6-diethyl-2-methyl-1,3-dihydroinden-2-yl)amino]-1-hydroxyethyl]-1h-quinolin-2-one Chemical compound C1=2NC(=O)C=CC=2C([C@@H](O)CNC2(C)CC=3C=C(C(=CC=3C2)CC)CC)=CC=C1NCC1=CC=CC=C1 AHPFGQFVXABBSZ-LJAQVGFWSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 208000033116 Asbestos intoxication Diseases 0.000 description 1
- 206010064823 Asthmatic crisis Diseases 0.000 description 1
- 239000005711 Benzoic acid Substances 0.000 description 1
- 229940121786 Beta 2 adrenoreceptor agonist Drugs 0.000 description 1
- 102100040794 Beta-1 adrenergic receptor Human genes 0.000 description 1
- 101710181961 Beta-1 adrenergic receptor Proteins 0.000 description 1
- 206010006458 Bronchitis chronic Diseases 0.000 description 1
- 206010006482 Bronchospasm Diseases 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- GUBBJXHZZYTNKS-UHFFFAOYSA-N C(C)C=1C=C2CC(CC2=CC1CC)NC(C1=CC=CC=C1)=O.C(C1=CC=CC=C1)NC1CC2=CC(=C(C=C2C1)CC)CC Chemical compound C(C)C=1C=C2CC(CC2=CC1CC)NC(C1=CC=CC=C1)=O.C(C1=CC=CC=C1)NC1CC2=CC(=C(C=C2C1)CC)CC GUBBJXHZZYTNKS-UHFFFAOYSA-N 0.000 description 1
- FMDKAAASPFPLKS-HKBQPEDESA-N C(C1=CC=CC=C1)N(C[C@@H](C1=CC(=C(C=C1)OCC1=CC=CC=C1)NS(=O)(=O)C)CC(=O)O)C1(CC2=CC=CC=C2C1)C Chemical compound C(C1=CC=CC=C1)N(C[C@@H](C1=CC(=C(C=C1)OCC1=CC=CC=C1)NS(=O)(=O)C)CC(=O)O)C1(CC2=CC=CC=C2C1)C FMDKAAASPFPLKS-HKBQPEDESA-N 0.000 description 1
- LERNTVKEWCAPOY-VOGVJGKGSA-N C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 Chemical compound C[N+]1(C)[C@H]2C[C@H](C[C@@H]1[C@H]1O[C@@H]21)OC(=O)C(O)(c1cccs1)c1cccs1 LERNTVKEWCAPOY-VOGVJGKGSA-N 0.000 description 1
- KORNTPPJEAJQIU-KJXAQDMKSA-N Cabaser Chemical compound C1=CC([C@H]2C[C@H](CN(CC=C)[C@@H]2C2)C(=O)N(CCCN(C)C)C(=O)NCC)=C3C2=CNC3=C1 KORNTPPJEAJQIU-KJXAQDMKSA-N 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 1
- XJUZRXYOEPSWMB-UHFFFAOYSA-N Chloromethyl methyl ether Chemical compound COCCl XJUZRXYOEPSWMB-UHFFFAOYSA-N 0.000 description 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 description 1
- 206010012335 Dependence Diseases 0.000 description 1
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
- 208000000059 Dyspnea Diseases 0.000 description 1
- 206010013975 Dyspnoeas Diseases 0.000 description 1
- 206010014561 Emphysema Diseases 0.000 description 1
- ICMAFTSLXCXHRK-UHFFFAOYSA-N Ethyl pentanoate Chemical compound CCCCC(=O)OCC ICMAFTSLXCXHRK-UHFFFAOYSA-N 0.000 description 1
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
- 229910010084 LiAlH4 Inorganic materials 0.000 description 1
- 229930045534 Me ester-Cyclohexaneundecanoic acid Natural products 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 1
- 238000010934 O-alkylation reaction Methods 0.000 description 1
- 235000019502 Orange oil Nutrition 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 208000006399 Premature Obstetric Labor Diseases 0.000 description 1
- 206010036600 Premature labour Diseases 0.000 description 1
- 208000013616 Respiratory Distress Syndrome Diseases 0.000 description 1
- 208000037656 Respiratory Sounds Diseases 0.000 description 1
- 208000005793 Restless legs syndrome Diseases 0.000 description 1
- 201000010001 Silicosis Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 208000005279 Status Asthmaticus Diseases 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- 208000001871 Tachycardia Diseases 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 206010044565 Tremor Diseases 0.000 description 1
- 208000024780 Urticaria Diseases 0.000 description 1
- 206010052568 Urticaria chronic Diseases 0.000 description 1
- 206010047924 Wheezing Diseases 0.000 description 1
- BLAKAEFIFWAFGH-UHFFFAOYSA-N acetyl acetate;pyridine Chemical compound C1=CC=NC=C1.CC(=O)OC(C)=O BLAKAEFIFWAFGH-UHFFFAOYSA-N 0.000 description 1
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 1
- 239000012346 acetyl chloride Substances 0.000 description 1
- 230000002378 acidificating effect Effects 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 201000000028 adult respiratory distress syndrome Diseases 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000036428 airway hyperreactivity Effects 0.000 description 1
- 125000004183 alkoxy alkyl group Chemical group 0.000 description 1
- 150000001350 alkyl halides Chemical class 0.000 description 1
- 239000002168 alkylating agent Substances 0.000 description 1
- 229940100198 alkylating agent Drugs 0.000 description 1
- 208000002205 allergic conjunctivitis Diseases 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 description 1
- PYHXGXCGESYPCW-UHFFFAOYSA-N alpha-phenylbenzeneacetic acid Natural products C=1C=CC=CC=1C(C(=O)O)C1=CC=CC=C1 PYHXGXCGESYPCW-UHFFFAOYSA-N 0.000 description 1
- 208000028462 aluminosis Diseases 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 150000001412 amines Chemical class 0.000 description 1
- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 208000010123 anthracosis Diseases 0.000 description 1
- 229940121363 anti-inflammatory agent Drugs 0.000 description 1
- 229940124599 anti-inflammatory drug Drugs 0.000 description 1
- 229940065524 anticholinergics inhalants for obstructive airway diseases Drugs 0.000 description 1
- 239000006286 aqueous extract Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 206010003441 asbestosis Diseases 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 238000011914 asymmetric synthesis Methods 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 208000024998 atopic conjunctivitis Diseases 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 1
- 229940092714 benzenesulfonic acid Drugs 0.000 description 1
- 235000010233 benzoic acid Nutrition 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 1
- 229960002802 bromocriptine Drugs 0.000 description 1
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 description 1
- 239000004044 bronchoconstricting agent Substances 0.000 description 1
- 230000007885 bronchoconstriction Effects 0.000 description 1
- 230000003435 bronchoconstrictive effect Effects 0.000 description 1
- 230000005587 bubbling Effects 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 description 1
- 229960004596 cabergoline Drugs 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 125000004218 chloromethyl group Chemical group [H]C([H])(Cl)* 0.000 description 1
- 208000007451 chronic bronchitis Diseases 0.000 description 1
- 208000024376 chronic urticaria Diseases 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 239000003245 coal Substances 0.000 description 1
- 239000012230 colorless oil Substances 0.000 description 1
- 230000008602 contraction Effects 0.000 description 1
- 239000003246 corticosteroid Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000003493 decenyl group Chemical group [H]C([*])=C([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000006612 decyloxy group Chemical group 0.000 description 1
- 150000001991 dicarboxylic acids Chemical class 0.000 description 1
- 238000006073 displacement reaction Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000002330 electrospray ionisation mass spectrometry Methods 0.000 description 1
- 239000003480 eluent Substances 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 239000003623 enhancer Substances 0.000 description 1
- 238000006735 epoxidation reaction Methods 0.000 description 1
- FRYHCSODNHYDPU-UHFFFAOYSA-N ethanesulfonyl chloride Chemical compound CCS(Cl)(=O)=O FRYHCSODNHYDPU-UHFFFAOYSA-N 0.000 description 1
- UFUUKTWOUIIKQV-PBVYKCSPSA-N ethyl 2-[[(7s)-7-[[2-(3-chloro-4-hydroxyphenyl)-2-hydroxyethyl]amino]-5,6,7,8-tetrahydronaphthalen-2-yl]oxy]acetate Chemical compound N([C@H]1CCC2=CC=C(C=C2C1)OCC(=O)OCC)CC(O)C1=CC=C(O)C(Cl)=C1 UFUUKTWOUIIKQV-PBVYKCSPSA-N 0.000 description 1
- 230000005713 exacerbation Effects 0.000 description 1
- 230000001747 exhibiting effect Effects 0.000 description 1
- 208000024711 extrinsic asthma Diseases 0.000 description 1
- 229960002714 fluticasone Drugs 0.000 description 1
- MGNNYOODZCAHBA-GQKYHHCASA-N fluticasone Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(O)[C@@]2(C)C[C@@H]1O MGNNYOODZCAHBA-GQKYHHCASA-N 0.000 description 1
- VGGRCVDNFAQIKO-UHFFFAOYSA-N formic anhydride Chemical compound O=COC=O VGGRCVDNFAQIKO-UHFFFAOYSA-N 0.000 description 1
- 238000001640 fractional crystallisation Methods 0.000 description 1
- 239000001530 fumaric acid Substances 0.000 description 1
- 239000003862 glucocorticoid Substances 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 239000004312 hexamethylene tetramine Substances 0.000 description 1
- 235000010299 hexamethylene tetramine Nutrition 0.000 description 1
- 125000006038 hexenyl group Chemical group 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000004128 high performance liquid chromatography Methods 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 150000003840 hydrochlorides Chemical class 0.000 description 1
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
- 229940071870 hydroiodic acid Drugs 0.000 description 1
- 230000035874 hyperreactivity Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 208000027866 inflammatory disease Diseases 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 229960001361 ipratropium bromide Drugs 0.000 description 1
- KEWHKYJURDBRMN-ZEODDXGYSA-M ipratropium bromide hydrate Chemical compound O.[Br-].O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 KEWHKYJURDBRMN-ZEODDXGYSA-M 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 239000004310 lactic acid Substances 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 210000004072 lung Anatomy 0.000 description 1
- 230000004199 lung function Effects 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 208000008585 mastocytosis Diseases 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- WSFSSNUMVMOOMR-NJFSPNSNSA-N methanone Chemical compound O=[14CH2] WSFSSNUMVMOOMR-NJFSPNSNSA-N 0.000 description 1
- AHADSRNLHOHMQK-UHFFFAOYSA-N methylidenecopper Chemical compound [Cu].[C] AHADSRNLHOHMQK-UHFFFAOYSA-N 0.000 description 1
- GRVDJDISBSALJP-UHFFFAOYSA-N methyloxidanyl Chemical compound [O]C GRVDJDISBSALJP-UHFFFAOYSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- QLSQLLWCWXTFMT-UHFFFAOYSA-N n-(2,5,6-trimethyl-1,3-dihydroinden-2-yl)benzamide Chemical compound C1C=2C=C(C)C(C)=CC=2CC1(C)NC(=O)C1=CC=CC=C1 QLSQLLWCWXTFMT-UHFFFAOYSA-N 0.000 description 1
- IDCXDGKYLGZRHK-UHFFFAOYSA-N n-(2-methyl-1,3-dihydroinden-2-yl)benzamide Chemical compound C1C2=CC=CC=C2CC1(C)NC(=O)C1=CC=CC=C1 IDCXDGKYLGZRHK-UHFFFAOYSA-N 0.000 description 1
- GVSNHWPUEYOYEY-UHFFFAOYSA-N n-(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)benzamide Chemical compound C1C=2C=C(CC)C(CC)=CC=2CC1NC(=O)C1=CC=CC=C1 GVSNHWPUEYOYEY-UHFFFAOYSA-N 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- MSZJJGHZRBKVHQ-UHFFFAOYSA-N n-[5-(2-bromoacetyl)-2-phenylmethoxyphenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC(C(=O)CBr)=CC=C1OCC1=CC=CC=C1 MSZJJGHZRBKVHQ-UHFFFAOYSA-N 0.000 description 1
- OZLPGJZEXODCGK-XIFFEERXSA-N n-[5-[(1r)-2-[benzyl-(2,5,6-trimethyl-1,3-dihydroinden-2-yl)amino]-1-hydroxyethyl]-2-phenylmethoxyphenyl]formamide Chemical compound O=CNC1=CC([C@@H](O)CN(C2(C)CC=3C=C(C(=CC=3C2)C)C)CC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 OZLPGJZEXODCGK-XIFFEERXSA-N 0.000 description 1
- XIXAVVCGASBSLO-XIFFEERXSA-N n-[5-[(1r)-2-[benzyl-(2,5,6-trimethyl-1,3-dihydroinden-2-yl)amino]-1-hydroxyethyl]-2-phenylmethoxyphenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC([C@@H](O)CN(C2(C)CC=3C=C(C(=CC=3C2)C)C)CC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 XIXAVVCGASBSLO-XIFFEERXSA-N 0.000 description 1
- ARWGSVNCUVQXQY-YTTGMZPUSA-N n-[5-[(1r)-2-[benzyl-(2-methyl-1,3-dihydroinden-2-yl)amino]-1-hydroxyethyl]-2-phenylmethoxyphenyl]ethanesulfonamide Chemical compound CCS(=O)(=O)NC1=CC([C@@H](O)CN(CC=2C=CC=CC=2)C2(C)CC3=CC=CC=C3C2)=CC=C1OCC1=CC=CC=C1 ARWGSVNCUVQXQY-YTTGMZPUSA-N 0.000 description 1
- CVBCNPSXNWYGKL-HKBQPEDESA-N n-[5-[(1r)-2-[benzyl-(2-methyl-1,3-dihydroinden-2-yl)amino]-1-hydroxyethyl]-2-phenylmethoxyphenyl]methanesulfonamide Chemical compound CS(=O)(=O)NC1=CC([C@@H](O)CN(C2(CC3=CC=CC=C3C2)C)CC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 CVBCNPSXNWYGKL-HKBQPEDESA-N 0.000 description 1
- CRBXCSYSBJOBHY-XIFFEERXSA-N n-[5-[(1r)-2-[benzyl-(2-methyl-1,3-dihydroinden-2-yl)amino]-1-hydroxyethyl]-2-phenylmethoxyphenyl]propane-1-sulfonamide Chemical compound CCCS(=O)(=O)NC1=CC([C@@H](O)CN(CC=2C=CC=CC=2)C2(C)CC3=CC=CC=C3C2)=CC=C1OCC1=CC=CC=C1 CRBXCSYSBJOBHY-XIFFEERXSA-N 0.000 description 1
- SMMPEAZCZUQMBQ-DHUJRADRSA-N n-[5-[(1r)-2-[benzyl-(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-2-phenylmethoxyphenyl]formamide Chemical compound O=CNC1=CC([C@@H](O)CN(C2CC=3C=C(C(=CC=3C2)CC)CC)CC=2C=CC=CC=2)=CC=C1OCC1=CC=CC=C1 SMMPEAZCZUQMBQ-DHUJRADRSA-N 0.000 description 1
- ILRVSCWHZDXBBK-UHFFFAOYSA-N n-[5-[2-[(2-ethyl-1,3-dihydroinden-2-yl)amino]-1-hydroxyethyl]-2-phenylmethoxyphenyl]methanesulfonamide Chemical compound C1C2=CC=CC=C2CC1(CC)NCC(O)C(C=C1NS(C)(=O)=O)=CC=C1OCC1=CC=CC=C1 ILRVSCWHZDXBBK-UHFFFAOYSA-N 0.000 description 1
- VHBMOKZHDBRJLZ-UHFFFAOYSA-N n-[5-[2-[(2-ethyl-1,3-dihydroinden-2-yl)amino]acetyl]-2-phenylmethoxyphenyl]methanesulfonamide Chemical compound C1C2=CC=CC=C2CC1(CC)NCC(=O)C(C=C1NS(C)(=O)=O)=CC=C1OCC1=CC=CC=C1 VHBMOKZHDBRJLZ-UHFFFAOYSA-N 0.000 description 1
- KSAZQVMKZMCKMM-UHFFFAOYSA-N n-[5-[2-[benzyl-(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]-1-hydroxyethyl]-2-phenylmethoxyphenyl]methanesulfonamide Chemical compound C1C=2C=C(CC)C(CC)=CC=2CC1N(CC=1C=CC=CC=1)CC(O)C(C=C1NS(C)(=O)=O)=CC=C1OCC1=CC=CC=C1 KSAZQVMKZMCKMM-UHFFFAOYSA-N 0.000 description 1
- GLWWACUXOQHITJ-UHFFFAOYSA-N n-[5-[2-[benzyl-(5,6-diethyl-2,3-dihydro-1h-inden-2-yl)amino]acetyl]-2-phenylmethoxyphenyl]methanesulfonamide Chemical compound C1C=2C=C(CC)C(CC)=CC=2CC1N(CC=1C=CC=CC=1)CC(=O)C(C=C1NS(C)(=O)=O)=CC=C1OCC1=CC=CC=C1 GLWWACUXOQHITJ-UHFFFAOYSA-N 0.000 description 1
- ZGFSCMUPBOLQQG-UHFFFAOYSA-N n-benzyl-2-methyl-1,3-dihydroinden-2-amine Chemical compound C1C2=CC=CC=C2CC1(C)NCC1=CC=CC=C1 ZGFSCMUPBOLQQG-UHFFFAOYSA-N 0.000 description 1
- DPUYSZJVGFTTMX-UHFFFAOYSA-N n-benzyl-6,7,8,9-tetrahydro-5h-benzo[7]annulen-7-amine Chemical compound C1CC2=CC=CC=C2CCC1NCC1=CC=CC=C1 DPUYSZJVGFTTMX-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- 125000005187 nonenyl group Chemical group C(=CCCCCCCC)* 0.000 description 1
- 125000001400 nonyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000004365 octenyl group Chemical group C(=CCCCCCC)* 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 239000006186 oral dosage form Substances 0.000 description 1
- 239000010502 orange oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- NFHFRUOZVGFOOS-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 NFHFRUOZVGFOOS-UHFFFAOYSA-N 0.000 description 1
- QNGNSVIICDLXHT-UHFFFAOYSA-N para-ethylbenzaldehyde Natural products CCC1=CC=C(C=O)C=C1 QNGNSVIICDLXHT-UHFFFAOYSA-N 0.000 description 1
- 125000002255 pentenyl group Chemical group C(=CCCC)* 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 230000000737 periodic effect Effects 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 230000035935 pregnancy Effects 0.000 description 1
- 208000026440 premature labor Diseases 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- KPBSJEBFALFJTO-UHFFFAOYSA-N propane-1-sulfonyl chloride Chemical compound CCCS(Cl)(=O)=O KPBSJEBFALFJTO-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 238000000159 protein binding assay Methods 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000010791 quenching Methods 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 229960001879 ropinirole Drugs 0.000 description 1
- UHSKFQJFRQCDBE-UHFFFAOYSA-N ropinirole Chemical compound CCCN(CCC)CCC1=CC=CC2=C1CC(=O)N2 UHSKFQJFRQCDBE-UHFFFAOYSA-N 0.000 description 1
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000003333 secondary alcohols Chemical class 0.000 description 1
- 208000004003 siderosis Diseases 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 1
- 239000012265 solid product Substances 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 239000012258 stirred mixture Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003460 sulfonic acids Chemical class 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 235000011149 sulphuric acid Nutrition 0.000 description 1
- 238000002636 symptomatic treatment Methods 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 230000006794 tachycardia Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229960000257 tiotropium bromide Drugs 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 230000037317 transdermal delivery Effects 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 238000000825 ultraviolet detection Methods 0.000 description 1
- 210000004291 uterus Anatomy 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- XOOUIPVCVHRTMJ-UHFFFAOYSA-L zinc stearate Chemical compound [Zn+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O XOOUIPVCVHRTMJ-UHFFFAOYSA-L 0.000 description 1
Classifications
-
- 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
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/02—Nasal agents, e.g. decongestants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
-
- 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
-
- 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
- A61P15/06—Antiabortive agents; Labour repressants
-
- 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
-
- 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
- A61P25/02—Drugs for disorders of the nervous system for peripheral neuropathies
-
- 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
- A61P37/00—Drugs for immunological or allergic disorders
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C215/00—Compounds containing amino and hydroxy groups bound to the same carbon skeleton
- C07C215/74—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton
- C07C215/76—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton of the same non-condensed six-membered aromatic ring
- C07C215/80—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups and amino groups bound to carbon atoms of six-membered aromatic rings of the same carbon skeleton of the same non-condensed six-membered aromatic ring containing at least two amino groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C233/00—Carboxylic acid amides
- C07C233/01—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C233/34—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups
- C07C233/42—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring
- C07C233/43—Carboxylic acid amides having carbon atoms of carboxamide groups bound to hydrogen atoms or to acyclic carbon atoms having the nitrogen atom of at least one of the carboxamide groups bound to a carbon atom of a hydrocarbon radical substituted by amino groups with the substituted hydrocarbon radical bound to the nitrogen atom of the carboxamide group by a carbon atom of a six-membered aromatic ring having the carbon atom of the carboxamide group bound to a hydrogen atom or to a carbon atom of a saturated carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/22—Oxygen atoms attached in position 2 or 4
- C07D215/227—Oxygen atoms attached in position 2 or 4 only one oxygen atom which is attached in position 2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms 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
- C07D215/20—Oxygen atoms
- C07D215/24—Oxygen atoms attached in position 8
- C07D215/26—Alcohols; Ethers thereof
-
- 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
- C07D405/12—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 linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Pulmonology (AREA)
- Endocrinology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Immunology (AREA)
- Biomedical Technology (AREA)
- Reproductive Health (AREA)
- Rheumatology (AREA)
- Pregnancy & Childbirth (AREA)
- Gynecology & Obstetrics (AREA)
- Otolaryngology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Quinoline Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9913083 | 1999-06-04 | ||
GBGB9913083.3A GB9913083D0 (en) | 1999-06-04 | 1999-06-04 | Organic compounds |
Publications (1)
Publication Number | Publication Date |
---|---|
ES2331457T3 true ES2331457T3 (es) | 2010-01-05 |
Family
ID=10854788
Family Applications (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES00935163T Expired - Lifetime ES2331457T3 (es) | 1999-06-04 | 2000-06-02 | Agonistas de beta2-adrenoceptor. |
ES08171523T Expired - Lifetime ES2402535T3 (es) | 1999-06-04 | 2000-06-02 | Agonista del Beta2-adrenoceptor |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
ES08171523T Expired - Lifetime ES2402535T3 (es) | 1999-06-04 | 2000-06-02 | Agonista del Beta2-adrenoceptor |
Country Status (38)
Country | Link |
---|---|
US (9) | US6878721B1 (en]) |
EP (2) | EP2332915B1 (en]) |
JP (1) | JP3785365B2 (en]) |
KR (1) | KR100718615B1 (en]) |
CN (1) | CN1156451C (en]) |
AR (1) | AR035548A1 (en]) |
AT (1) | ATE440083T1 (en]) |
AU (1) | AU765919B2 (en]) |
BE (1) | BE2010C011I2 (en]) |
BR (1) | BRPI0011324B8 (en]) |
CA (1) | CA2375810C (en]) |
CO (1) | CO5170518A1 (en]) |
CY (3) | CY1109604T1 (en]) |
CZ (1) | CZ302403B6 (en]) |
DE (2) | DE122010000009I2 (en]) |
DK (2) | DK2332915T3 (en]) |
ES (2) | ES2331457T3 (en]) |
FR (1) | FR10C0006I2 (en]) |
GB (1) | GB9913083D0 (en]) |
HK (1) | HK1045837B (en]) |
HU (1) | HU227034B1 (en]) |
IL (2) | IL146578A0 (en]) |
LU (1) | LU91651I2 (en]) |
MX (1) | MXPA01012474A (en]) |
MY (1) | MY126951A (en]) |
NL (1) | NL300437I1 (en]) |
NO (2) | NO322944B1 (en]) |
NZ (1) | NZ515669A (en]) |
PE (1) | PE20010219A1 (en]) |
PL (1) | PL198847B1 (en]) |
PT (2) | PT1183240E (en]) |
RU (1) | RU2244709C2 (en]) |
SI (1) | SI1183240T1 (en]) |
SK (1) | SK287260B6 (en]) |
TR (1) | TR200103497T2 (en]) |
TW (1) | TWI253447B (en]) |
WO (1) | WO2000075114A1 (en]) |
ZA (1) | ZA200109931B (en]) |
Families Citing this family (180)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AR028948A1 (es) | 2000-06-20 | 2003-05-28 | Astrazeneca Ab | Compuestos novedosos |
GB0029562D0 (en) * | 2000-12-04 | 2001-01-17 | Novartis Ag | Organic compounds |
TWI243164B (en) | 2001-02-13 | 2005-11-11 | Aventis Pharma Gmbh | Acylated indanyl amines and their use as pharmaceuticals |
GB0121214D0 (en) * | 2001-08-31 | 2001-10-24 | Btg Int Ltd | Synthetic method |
TWI249515B (en) | 2001-11-13 | 2006-02-21 | Theravance Inc | Aryl aniline beta2 adrenergic receptor agonists |
WO2003042160A1 (en) | 2001-11-13 | 2003-05-22 | Theravance, Inc. | Aryl aniline beta-2 adrenergic receptor agonists |
EP2311818B1 (en) | 2002-02-28 | 2013-01-16 | Novartis AG | Combination of a 5-phenylthiazole compound as PI3 kinase inhibitor with an antiinflammatory, bronchodilatory or antihistamine drug |
US6933410B2 (en) | 2002-03-08 | 2005-08-23 | Novartis Ag | Process for preparing 5,6-diethyl-2,3-dihydro-1H-inden-2-amine |
US7250426B2 (en) * | 2002-11-29 | 2007-07-31 | Boehringer Ingelheim Pharma Gmbh & Co Kg | Tiotropium-containing pharmaceutical combination for inhalation |
DE10256080A1 (de) * | 2002-11-29 | 2004-06-17 | Boehringer Ingelheim Pharma Gmbh & Co. Kg | Tiotropiumhaltige Arzneimittelkombination für die Inhalation |
PE20040950A1 (es) | 2003-02-14 | 2005-01-01 | Theravance Inc | DERIVADOS DE BIFENILO COMO AGONISTAS DE LOS RECEPTORES ADRENERGICOS ß2 Y COMO ANTAGONISTAS DE LOS RECEPTORES MUSCARINICOS |
TWI324150B (en) * | 2003-02-28 | 2010-05-01 | Novartis Ag | Process for preparing 5-[(r)-2-(5,6-diethyl-indan-2-ylamino)-1-hydroxy-ethyl]-8-hydroxy-(1h)-quinolin-2-one salt |
PE20050211A1 (es) * | 2003-04-02 | 2005-04-27 | Novartis Ag | Procedimiento para preparar oxi-(1h)-quinolin-2-onas 5-(alfa-haloacetil)-8-sustituidas |
PL1613315T3 (pl) * | 2003-04-04 | 2009-07-31 | Novartis Ag | Pochodne chinolino-2-onu do leczenia chorób dróg oddechowych |
GB0307856D0 (en) * | 2003-04-04 | 2003-05-14 | Novartis Ag | Organic compounds |
AR044519A1 (es) | 2003-05-02 | 2005-09-14 | Novartis Ag | Derivados de piridin-tiazol amina y de pirimidin-tiazol amina |
PT1651270E (pt) * | 2003-07-29 | 2007-04-30 | Boehringer Ingelheim Int | Medicamentos para inalação compreendendo betamiméticos e um anticolinérgico |
TW200526547A (en) | 2003-09-22 | 2005-08-16 | Theravance Inc | Amino-substituted ethylamino β2 adrenergic receptor agonists |
TW200531692A (en) | 2004-01-12 | 2005-10-01 | Theravance Inc | Aryl aniline derivatives as β2 adrenergic receptor agonists |
GB0401334D0 (en) | 2004-01-21 | 2004-02-25 | Novartis Ag | Organic compounds |
WO2005092861A1 (en) * | 2004-03-11 | 2005-10-06 | Pfizer Limited | Quinolinone derivatives pharmaceutical compositions containing them and their use |
EP1574501A1 (en) * | 2004-03-11 | 2005-09-14 | Pfizer Limited | Quinolinone derivatives, pharmaceutical compositions containing them and their use |
WO2005089718A2 (en) * | 2004-03-23 | 2005-09-29 | Novartis Ag | Pharmaceutical compositions |
GB0410712D0 (en) | 2004-05-13 | 2004-06-16 | Novartis Ag | Organic compounds |
GB0411056D0 (en) * | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
ES2257152B1 (es) * | 2004-05-31 | 2007-07-01 | Laboratorios Almirall S.A. | Combinaciones que comprenden agentes antimuscarinicos y agonistas beta-adrenergicos. |
GB0413960D0 (en) * | 2004-06-22 | 2004-07-28 | Novartis Ag | Organic compounds |
US7566785B2 (en) * | 2004-09-10 | 2009-07-28 | Theravance, Inc. | Amidine substituted aryl aniline compounds |
GT200500281A (es) | 2004-10-22 | 2006-04-24 | Novartis Ag | Compuestos organicos. |
GB0424284D0 (en) | 2004-11-02 | 2004-12-01 | Novartis Ag | Organic compounds |
GB0426164D0 (en) | 2004-11-29 | 2004-12-29 | Novartis Ag | Organic compounds |
GB0507577D0 (en) | 2005-04-14 | 2005-05-18 | Novartis Ag | Organic compounds |
GB0510390D0 (en) | 2005-05-20 | 2005-06-29 | Novartis Ag | Organic compounds |
GB0511066D0 (en) * | 2005-05-31 | 2005-07-06 | Novartis Ag | Organic compounds |
GB0511065D0 (en) * | 2005-05-31 | 2005-07-06 | Novartis Ag | Organic compounds |
TW200738634A (en) | 2005-08-02 | 2007-10-16 | Astrazeneca Ab | New salt |
GB0516313D0 (en) | 2005-08-08 | 2005-09-14 | Argenta Discovery Ltd | Azole derivatives and their uses |
EP2281813A1 (en) | 2005-08-08 | 2011-02-09 | Pulmagen Therapeutics (Synergy) Limited | Bicyclo[2.2.1]hept-7-ylamine derivatives and their uses |
TW200738658A (en) | 2005-08-09 | 2007-10-16 | Astrazeneca Ab | Novel compounds |
BRPI0615064A2 (pt) * | 2005-08-26 | 2011-05-03 | Astrazeneca Ab | combinação de compostos que pode ser usada no tratamento de doenças respiratórias, especialmente, doença pulmonar obstrutiva crÈnica (dpoc) e asma |
AU2006303452B2 (en) | 2005-10-21 | 2011-06-09 | Novartis Ag | Human antibodies against IL13 and therapeutic uses |
TWI392493B (zh) * | 2005-10-26 | 2013-04-11 | Novartis Ag | 格隆溴銨(GLYCOPYRROLATE)及β2腎上腺素受體激動劑之組合 |
GB0525671D0 (en) | 2005-12-16 | 2006-01-25 | Novartis Ag | Organic compounds |
GB0526244D0 (en) | 2005-12-22 | 2006-02-01 | Novartis Ag | Organic compounds |
JO2660B1 (en) | 2006-01-20 | 2012-06-17 | نوفارتيس ايه جي | Pi-3 inhibitors and methods of use |
GB0601951D0 (en) | 2006-01-31 | 2006-03-15 | Novartis Ag | Organic compounds |
GB0602778D0 (en) | 2006-02-10 | 2006-03-22 | Glaxo Group Ltd | Novel compound |
TW200745067A (en) | 2006-03-14 | 2007-12-16 | Astrazeneca Ab | Novel compounds |
PT2013211E (pt) | 2006-04-21 | 2012-06-21 | Novartis Ag | Derivados de purina para utilização como agonistas de receptores a2a de adenosina |
CA2654801C (en) * | 2006-06-30 | 2014-08-19 | Novartis Ag | Quinolinone derivatives and their pharmaceutical compositions |
EP1878722A1 (en) * | 2006-07-13 | 2008-01-16 | Novartis AG | Quinolinone derivatives and their pharmaceutical compositions |
EP1914227A1 (en) * | 2006-08-31 | 2008-04-23 | Novartis AG | Polymorphic crystal form of a indan-2-ylamino-hydroxyethyl-quinolinone maleate derivative as beta-adrenoceptor agonist |
RU2009115954A (ru) | 2006-09-29 | 2010-11-10 | Новартис АГ (CH) | Пиразолопиримидины в качестве ингибиторов липидной киназы р13к |
KR20090075714A (ko) | 2006-10-30 | 2009-07-08 | 노파르티스 아게 | 소염제로서의 헤테로시클릭 화합물 |
TW200833670A (en) | 2006-12-20 | 2008-08-16 | Astrazeneca Ab | Novel compounds 569 |
PL2104535T3 (pl) | 2007-01-10 | 2011-05-31 | Irm Llc | Związki i kompozycje jako inhibitory proteazy aktywujące kanały |
GB0702458D0 (en) | 2007-02-08 | 2007-03-21 | Astrazeneca Ab | Salts 668 |
EA200901082A1 (ru) | 2007-02-09 | 2010-02-26 | Айрм Ллк | Соединения и композиции в качестве ингибиторов протеазы, активирующей каналы |
DE602008005140D1 (de) | 2007-05-07 | 2011-04-07 | Novartis Ag | Organische verbindungen |
ES2654395T3 (es) | 2007-12-10 | 2018-02-13 | Novartis Ag | Análogos de amilorida espirocíclicos como bloqueantes de ENaC |
PT2231642E (pt) | 2008-01-11 | 2014-03-12 | Novartis Ag | Pirimidinas como inibidores de quinase |
US8268834B2 (en) | 2008-03-19 | 2012-09-18 | Novartis Ag | Pyrazine derivatives that inhibit phosphatidylinositol 3-kinase enzyme |
CA2727196A1 (en) | 2008-06-10 | 2009-12-17 | Novartis Ag | Organic compounds |
EA201001747A1 (ru) | 2008-06-18 | 2011-08-30 | Астразенека Аб | Бензоксазиноновые производные, действующие в качестве агониста бета-2-адренорецептора, для лечения респираторных расстройств |
US8236786B2 (en) | 2008-08-07 | 2012-08-07 | Pulmagen Therapeutics (Inflammation) Limited | Respiratory disease treatment |
BRPI0923862A2 (pt) | 2008-12-30 | 2015-07-28 | Pulmagen Therapeutics Inflammation Ltd | Compostos sulfonamida para o tratamento de distúrbios respiratórios |
JP2012516345A (ja) | 2009-01-29 | 2012-07-19 | ノバルティス アーゲー | 星細胞腫治療用置換ベンゾイミダゾール |
AR075401A1 (es) * | 2009-02-13 | 2011-03-30 | Sanofi Aventis | Indanos sustituidos, procesos para su preparacion y uso de los mismos como un medicamento |
WO2010150014A1 (en) | 2009-06-24 | 2010-12-29 | Pulmagen Therapeutics (Inflammation) Limited | 5r- 5 -deuterated glitazones for respiratory disease treatment |
US8389526B2 (en) | 2009-08-07 | 2013-03-05 | Novartis Ag | 3-heteroarylmethyl-imidazo[1,2-b]pyridazin-6-yl derivatives |
US8497368B2 (en) | 2009-08-12 | 2013-07-30 | Novartis Ag | Heterocyclic hydrazone compounds |
EA026693B1 (ru) | 2009-08-17 | 2017-05-31 | Интелликайн ЭлЭлСи | Производные бензоксазола и бензотиазола в качестве ингибиторов pi3-киназы |
JP5775871B2 (ja) | 2009-08-20 | 2015-09-09 | ノバルティス アーゲー | ヘテロ環式オキシム化合物 |
CA2777245A1 (en) | 2009-10-22 | 2011-04-28 | Vertex Pharmaceuticals Incorporated | Compositions for treatment of cystic fibrosis and other chronic diseases |
GB0918924D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Azaindole derivatives |
GB0918922D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminopyridine derivatives |
GB0918923D0 (en) | 2009-10-28 | 2009-12-16 | Vantia Ltd | Aminothiazole derivatives |
WO2011056929A1 (en) | 2009-11-04 | 2011-05-12 | Massachusetts Institute Of Technology | Continuous flow synthesis of amino alcohols using microreactors |
WO2011098746A1 (en) | 2010-02-09 | 2011-08-18 | Pulmagen Therapeutics (Inflammation) Limited | Crystalline acid addition salts of ( 5r) -enanti0mer of pioglitazone |
GB201002224D0 (en) | 2010-02-10 | 2010-03-31 | Argenta Therapeutics Ltd | Respiratory disease treatment |
GB201002243D0 (en) | 2010-02-10 | 2010-03-31 | Argenta Therapeutics Ltd | Respiratory disease treatment |
US9012452B2 (en) * | 2010-02-18 | 2015-04-21 | Astrazeneca Ab | Processes for making cyclopropyl amide derivatives and intermediates associated therewith |
US8680303B2 (en) | 2010-03-01 | 2014-03-25 | Massachusetts Institute Of Technology | Epoxidation catalysts |
US8247436B2 (en) | 2010-03-19 | 2012-08-21 | Novartis Ag | Pyridine and pyrazine derivative for the treatment of CF |
US8754085B2 (en) | 2010-07-14 | 2014-06-17 | Novartis Ag | Pyrido[2,3-b]pyrazine compounds useful as IP receptor agonist |
WO2012034095A1 (en) | 2010-09-09 | 2012-03-15 | Irm Llc | Compounds and compositions as trk inhibitors |
UY33597A (es) | 2010-09-09 | 2012-04-30 | Irm Llc | Compuestos y composiciones como inhibidores de la trk |
US8372845B2 (en) | 2010-09-17 | 2013-02-12 | Novartis Ag | Pyrazine derivatives as enac blockers |
CN103269694A (zh) | 2010-10-12 | 2013-08-28 | 西普拉有限公司 | 药物组合物 |
JOP20120023B1 (ar) | 2011-02-04 | 2022-03-14 | Novartis Ag | صياغات مساحيق جافة من جسيمات تحتوي على واحد أو اثنين من المواد الفعالة لعلاج امراض ممرات الهواء الانسدادية او الالتهابية |
JP2014505088A (ja) | 2011-02-10 | 2014-02-27 | ノバルティス アーゲー | C−METチロシンキナーゼ阻害剤としての[1,2,4]トリアゾロ[4,3−b]ピリダジン化合物 |
WO2012116237A2 (en) | 2011-02-23 | 2012-08-30 | Intellikine, Llc | Heterocyclic compounds and uses thereof |
AU2012220572A1 (en) | 2011-02-25 | 2013-08-29 | Irm Llc | Compounds and compositions as trk inhibitors |
UY34305A (es) | 2011-09-01 | 2013-04-30 | Novartis Ag | Derivados de heterociclos bicíclicos para el tratamiento de la hipertensión arterial pulmonar |
AU2012310168B2 (en) | 2011-09-15 | 2015-07-16 | Novartis Ag | 6 - substituted 3 - (quinolin- 6 - ylthio) - [1,2,4] triazolo [4, 3 -a] pyradines as tyrosine kinase |
US9034879B2 (en) | 2011-09-16 | 2015-05-19 | Novartis Ag | Heterocyclic compounds for the treatment of CF |
WO2013038373A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
WO2013038378A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine amide derivatives |
WO2013038381A1 (en) | 2011-09-16 | 2013-03-21 | Novartis Ag | Pyridine/pyrazine amide derivatives |
JP6165733B2 (ja) | 2011-09-16 | 2017-07-19 | ノバルティス アーゲー | N−置換ヘテロシクリルカルボキサミド類 |
CN104363914A (zh) | 2011-11-23 | 2015-02-18 | 因特利凯有限责任公司 | 使用mTOR抑制剂的增强的治疗方案 |
US9115129B2 (en) | 2012-01-13 | 2015-08-25 | Novartis Ag | Substituted pyrido[2,3-B]pyrazines as IP receptor agonists |
US8937069B2 (en) | 2012-01-13 | 2015-01-20 | Novartis Ag | Substituted pyrrolo[2,3-B]pyrazine compounds and their use |
ES2561353T3 (es) | 2012-01-13 | 2016-02-25 | Novartis Ag | Sales de un agonista del receptor IP |
EP2802582A1 (en) | 2012-01-13 | 2014-11-19 | Novartis AG | Fused dihydropyrido [2,3 -b]pyrazines as ip receptor agonists for the treatment of pulmonary arterial hypertension (pah) and related disorders |
EP2802581A1 (en) | 2012-01-13 | 2014-11-19 | Novartis AG | 7,8- dihydropyrido [3, 4 - b]pyrazines as ip receptor agonists for the treatment of pulmonary arterial hypertension (pah) and related disorders |
WO2013105063A1 (en) | 2012-01-13 | 2013-07-18 | Novartis Ag | Fused piperidines as ip receptor agonists for the treatment of pulmonary arterial hypertension (pah) and related disorders |
WO2013132514A2 (en) * | 2012-03-09 | 2013-09-12 | Rao Davuluri Ramamohan | A novel process for the preparation of (r)-5-[2-[(5, 6-diethyl-2, 3-dihydro-1h-inden-2-yl) amino]-1-hydroxyethyl]-8-hydroxy quinolin-2(1h)-one |
US8809340B2 (en) | 2012-03-19 | 2014-08-19 | Novartis Ag | Crystalline form |
AU2013243097A1 (en) | 2012-04-03 | 2014-10-09 | Novartis Ag | Combination products with tyrosine kinase inhibitors and their use |
WO2014008639A1 (zh) * | 2012-07-11 | 2014-01-16 | 上海威智医药科技有限公司 | 制备茚达特罗的方法 |
WO2014008640A1 (zh) * | 2012-07-11 | 2014-01-16 | 上海威智医药科技有限公司 | 茚达特罗中间体及茚达特罗的合成方法 |
CN103539677B (zh) * | 2012-07-16 | 2015-04-22 | 武汉万知生物医药有限公司 | 一种5,6-二乙基-2,3-二氢-1h-茚-2-胺盐酸盐的制备方法 |
WO2014044288A1 (en) * | 2012-09-21 | 2014-03-27 | Crystal Pharma Sa | Methods for the preparation of indacaterol and pharmaceutically acceptable salts thereof |
EP3848354B1 (en) | 2012-09-21 | 2022-07-27 | Crystal Pharma, S.A.U. | Process for the preparation of indacaterol and intermediates thereof |
CN104968656B (zh) | 2012-12-19 | 2017-08-11 | 诺华股份有限公司 | 自分泌运动因子抑制剂 |
US9784726B2 (en) | 2013-01-08 | 2017-10-10 | Atrogi Ab | Screening method, a kit, a method of treatment and a compound for use in a method of treatment |
JP2016507582A (ja) | 2013-02-13 | 2016-03-10 | ノバルティス アーゲー | Ip受容体アゴニスト複素環式化合物 |
US9073921B2 (en) | 2013-03-01 | 2015-07-07 | Novartis Ag | Salt forms of bicyclic heterocyclic derivatives |
US9452139B2 (en) | 2013-03-14 | 2016-09-27 | Novartis Ag | Respirable agglomerates of porous carrier particles and micronized drug |
WO2014141069A1 (en) | 2013-03-14 | 2014-09-18 | Novartis Ag | Deamorphization of spray-dried formulations via spray-blending |
EP2968340A4 (en) | 2013-03-15 | 2016-08-10 | Intellikine Llc | COMBINING KINASE INHIBITORS AND USES THEREOF |
CZ306252B6 (cs) * | 2013-03-15 | 2016-10-26 | Zentiva, K.S. | Způsob přípravy 5-[(R)-2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-(1H)-chinolin-2-onu (indacaterolu) |
WO2014154841A1 (en) * | 2013-03-27 | 2014-10-02 | Laboratorios Lesvi, S.L. | Process for the manufacture of (r)-5-[2-(5,6-diethylindan-2-ylamino)-1-hydroxyethyl]-8-hydroxy-(1h)-quinolin-2-one |
TN2016000022A1 (en) | 2013-07-18 | 2017-07-05 | Novartis Ag | Autotaxin inhibitors comprising a heteroaromatic ring-benzyl-amide-cycle core |
WO2015008229A1 (en) | 2013-07-18 | 2015-01-22 | Novartis Ag | Autotaxin inhibitors |
TW201605450A (zh) | 2013-12-03 | 2016-02-16 | 諾華公司 | Mdm2抑制劑與BRAF抑制劑之組合及其用途 |
CN104744360B (zh) * | 2013-12-26 | 2017-02-22 | 成都伊诺达博医药科技有限公司 | 一种合成茚达特罗的新方法 |
EP3092217B1 (en) | 2014-01-09 | 2020-06-03 | Davuluri, Ramamohan Rao | A novel process for preparation of indacaterol or its pharmaceutically acceptable salts |
CN103830193A (zh) * | 2014-03-11 | 2014-06-04 | 熊妲妮 | 茚达特罗片制剂及其制备方法 |
CN103830195A (zh) * | 2014-03-11 | 2014-06-04 | 熊妲妮 | 一种茚达特罗片及其制备方法 |
WO2015145353A1 (en) | 2014-03-27 | 2015-10-01 | Novartis Ag | Spray-dried solid-in-oil-in-water dispersions for inhalation of active pharmaceutical ingredients |
CA2945069A1 (en) | 2014-04-24 | 2015-10-29 | Novartis Ag | Amino pyridine derivatives as phosphatidylinositol 3-kinase inhibitors |
US10004732B2 (en) | 2014-04-24 | 2018-06-26 | Novartis Ag | Amino pyrazine derivatives as phosphatidylinositol 3-kinase inhibitors |
CN106458966B (zh) | 2014-04-24 | 2019-05-07 | 诺华股份有限公司 | 作为磷脂酰肌醇3-激酶抑制剂的吡嗪衍生物 |
US20170037030A1 (en) | 2014-04-24 | 2017-02-09 | Novartis Ag | Autotaxin inhibitors |
WO2016011658A1 (en) | 2014-07-25 | 2016-01-28 | Novartis Ag | Combination therapy |
EP3174869B1 (en) | 2014-07-31 | 2020-08-19 | Novartis AG | Combination therapy of a met inhibitor and an egfr inhibitor |
DE102014217201A1 (de) | 2014-08-28 | 2016-03-03 | Henkel Ag & Co. Kgaa | Verwendung einer Kombination von Rheolate FX 1100 und Luviskol K90 |
DE102014217205A1 (de) | 2014-08-28 | 2016-03-03 | Henkel Ag & Co. Kgaa | Verwendung einer Kombination von Rheolate FX 1100 und Luviskol VA 64 W |
US11094409B2 (en) | 2015-01-20 | 2021-08-17 | Novartis Ag | Application unlock using a connected physical device and transfer of data therebetween |
CA2973318A1 (en) | 2015-01-20 | 2016-07-28 | Olon S.P.A. | Process for the preparation of indanamine derivatives and new synthesis intermediates |
CN107531636B (zh) * | 2015-04-09 | 2022-11-25 | 正大天晴药业集团股份有限公司 | 茚达特罗或其盐的制备方法 |
EP3111978B1 (en) | 2015-07-03 | 2021-09-01 | Novartis AG | Inhaler adapted to read information stored in a data storage means of a container |
ITUB20153978A1 (it) * | 2015-09-28 | 2017-03-28 | Laboratorio Chimico Int S P A | Procedimento per la preparazione di derivati di indanammina e di nuovi intermedi di sintesi. |
CN105884626B (zh) * | 2016-05-04 | 2017-10-20 | 龙曦宁(上海)医药科技有限公司 | 一种2‑氨基茚满衍生物的合成方法及其产品 |
CN108101841B (zh) * | 2016-11-24 | 2021-04-06 | 江苏恒瑞医药股份有限公司 | 一种制备茚达特罗或其盐的方法 |
GB201714736D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
GB201714740D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
GB201714745D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
GB201714734D0 (en) | 2017-09-13 | 2017-10-25 | Atrogi Ab | New compounds and uses |
EP3735406B1 (en) | 2018-01-02 | 2022-05-11 | Deva Holding Anonim Sirketi | A process for preparation of 5-(2-(substituted-amino)-1-hydroxyethyl)-8-(substituted-oxy) quinolin-2(1h)-one |
EP3768765B1 (en) | 2018-03-19 | 2023-05-17 | Dow Silicones Corporation | Polyolefin-polydiorganosiloxane block copolymer and hydrosilylaton reaction method for the synthesis thereof |
EP3768792B1 (en) | 2018-03-19 | 2023-09-20 | Dow Silicones Corporation | Hot melt adhesive composition containing a polyolefin - polydiorganosiloxane copolymer and methods for the preparation and use thereof |
JP7378416B2 (ja) | 2018-03-19 | 2023-11-13 | ダウ シリコーンズ コーポレーション | ポリオレフィン-ポリジオルガノシロキサンブロックコポリマーおよびその合成のための方法 |
CN111868196B (zh) | 2018-03-19 | 2022-08-30 | 美国陶氏有机硅公司 | 含有聚烯烃-聚二有机硅氧烷共聚物的聚有机硅氧烷热熔胶组合物和其制备和使用方法 |
JP7334195B2 (ja) | 2018-07-17 | 2023-08-28 | ダウ シリコーンズ コーポレーション | ポリシロキサン樹脂-ポリオレフィンコポリマー並びにその調製方法及び使用方法 |
WO2020047225A1 (en) | 2018-08-30 | 2020-03-05 | Theravance Biopharma R&D Ip, Llc | Methods for treating chronic obstructive pulmonary disease |
EP3860712A1 (en) | 2018-10-05 | 2021-08-11 | Vertex Pharmaceuticals Incorporated | Modulators of alpha-1 antitrypsin |
CN109369417B (zh) * | 2018-10-19 | 2021-07-06 | 诚达药业股份有限公司 | 一种2-氨基茚满衍生物的制备方法 |
US20200163955A1 (en) | 2018-11-22 | 2020-05-28 | Glenmark Specialty S.A. | Sterile compositions of indacaterol suitable for nebulization |
US20200215051A1 (en) | 2019-01-03 | 2020-07-09 | Glenmark Specialty S.A. | Nebulization composition comprising tiotropium and indacaterol |
GB201903832D0 (en) | 2019-03-20 | 2019-05-01 | Atrogi Ab | New compounds and methods |
CN109896967B (zh) * | 2019-04-04 | 2021-10-22 | 上海工程技术大学 | 一种间二乙氨基苯酚的制备方法 |
CN109896966B (zh) * | 2019-04-04 | 2021-10-22 | 上海工程技术大学 | 一种n,n-二丁基间氨基苯酚的制备方法 |
UY38696A (es) | 2019-05-14 | 2020-11-30 | Vertex Pharma | Moduladores de alfa-1 antitripsina |
CN110229078A (zh) * | 2019-05-22 | 2019-09-13 | 博诺康源(北京)药业科技有限公司 | 一种茚达特罗起始原料开环杂质的制备 |
KR20220019015A (ko) | 2019-06-10 | 2022-02-15 | 노파르티스 아게 | Cf, copd, 및 기관지확장증 치료를 위한 피리딘 및 피라진 유도체 |
PH12022550468A1 (en) | 2019-08-28 | 2023-03-06 | Novartis Ag | Substituted 1,3-phenyl heteroaryl derivatives and their use in the treatment of disease |
TW202140550A (zh) | 2020-01-29 | 2021-11-01 | 瑞士商諾華公司 | 使用抗tslp抗體治療炎性或阻塞性氣道疾病之方法 |
CN115697969A (zh) * | 2020-04-03 | 2023-02-03 | 弗特克斯药品有限公司 | 作为用于治疗α-1抗胰蛋白酶缺乏症(AATD)的α-1抗胰蛋白酶调节剂的7-或8-羟基-异喹啉和7-或8-羟基-喹啉衍生物 |
CA3185469A1 (en) | 2020-08-14 | 2022-02-17 | Novartis Ag | Heteroaryl substituted spiropiperidinyl derivatives and pharmaceutical uses thereof |
CN116963715A (zh) | 2020-09-29 | 2023-10-27 | 艾罗克斯医疗有限责任公司 | 茚达特罗的液体配制品 |
CN115677577B (zh) * | 2021-11-03 | 2024-11-15 | 中国药科大学 | 靶向srsf6蛋白的小分子化合物及其制备方法和用途 |
GB202205895D0 (en) | 2022-04-22 | 2022-06-08 | Atrogi Ab | New medical uses |
CN115521254B (zh) * | 2022-09-27 | 2024-05-31 | 中国药科大学 | 一种茚达特罗衍生物及其制备方法和应用 |
WO2024153813A1 (en) | 2023-01-20 | 2024-07-25 | Atrogi Ab | Beta 2-adrenergic receptor agonists for treatment or prevention of muscle wasting |
GB202302225D0 (en) | 2023-02-16 | 2023-04-05 | Atrogi Ab | New medical uses |
GB202303229D0 (en) | 2023-03-06 | 2023-04-19 | Atrogi Ab | New medical uses |
WO2024206662A1 (en) * | 2023-03-30 | 2024-10-03 | Aerorx Therapeutics Llc | Liquid formulations of indacaterol and glycopyrronium |
Family Cites Families (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE2354959C3 (de) * | 1973-11-02 | 1980-02-07 | Dr. Karl Thomae Gmbh, 7950 Biberach | Neues Verfahren zur Herstellung von 4-Amino-3,5 dihalogen phenyl-athanolaminen |
GB8707123D0 (en) | 1987-03-25 | 1987-04-29 | Pfizer Ltd | Antiarrhythmic agents |
ZA903906B (en) * | 1989-05-25 | 1992-02-26 | Takeda Chemical Industries Ltd | Benzocycloalkane derivatives and production thereof |
AU632809B2 (en) | 1989-05-25 | 1993-01-14 | Takeda Chemical Industries Ltd. | Benzocycloalkane benzopyran and benzothiopyran urea derivatives and production thereof |
CA2107682A1 (en) * | 1991-04-10 | 1992-10-11 | Javier Navarro | Interleukin-8 receptors and related molecules and methods |
GB9107827D0 (en) | 1991-04-12 | 1991-05-29 | Fujisawa Pharmaceutical Co | New ethanolamine derivatives,processes for the preparation thereof and pharmaceutical composition comprising the same |
JPH0518007A (ja) | 1991-07-05 | 1993-01-26 | Konoike Constr Ltd | 鉄骨梁との接合部を内蔵したpc柱 |
IL104567A (en) * | 1992-02-03 | 1997-03-18 | Fujisawa Pharmaceutical Co | Ethanolamine derivatives, processes for the preparation thereof and pharmaceutical compositions containing the same |
WO1993018007A1 (en) | 1992-03-13 | 1993-09-16 | Tokyo Tanabe Company Limited | Novel carbostyril derivative |
ES2115003T3 (es) | 1993-01-29 | 1998-06-16 | American Cyanamid Co | Aminocicloalcanobenzodioxoles como agentes adrenergicos selectivos beta-3. |
WO1995004713A1 (en) | 1993-08-06 | 1995-02-16 | The Upjohn Company | 2-aminoindans as selective dopamine d3 ligands |
FR2711407B1 (fr) * | 1993-10-19 | 1996-01-26 | Allevard Sa | Perfectionnements aux barres de torsion métalliques. |
US5578638A (en) | 1993-11-05 | 1996-11-26 | American Cyanamid Company | Treatment of glaucoma and ocular hypertension with β3 -adrenergic agonists |
GB9405019D0 (en) | 1994-03-15 | 1994-04-27 | Smithkline Beecham Plc | Novel compounds |
CZ285850B6 (cs) | 1995-02-01 | 1999-11-17 | Pharmacia & Upjohn Company | 2-Aminoindany jako selektivní dopaminové D3 ligandy |
ZA967892B (en) | 1995-09-21 | 1998-03-18 | Lilly Co Eli | Selective β3 adrenergic agonists. |
SG72727A1 (en) * | 1996-02-19 | 2000-05-23 | Kissei Pharmaceutical | 3,4-Disubstituted phenylethanolaminotetralincarboxamide derivatives |
JP3708624B2 (ja) * | 1996-03-27 | 2005-10-19 | キッセイ薬品工業株式会社 | 3,4−ジ置換フェニルエタノールアミノテトラリンカルボン酸誘導体 |
JP3690071B2 (ja) | 1997-06-24 | 2005-08-31 | 井関農機株式会社 | ロータリ耕耘具の防護装置 |
AU8562098A (en) * | 1997-08-19 | 1999-03-08 | Kissei Pharmaceutical Co. Ltd. | Phenylethanolaminotetralin derivatives and bronchodilators |
DE69940484D1 (de) | 1998-04-06 | 2009-04-09 | Astellas Pharma Inc | Verwendung von beta-3-adrenergen-Rezeptoren Agonisten in der Behandlung von Dysurie |
DE20122417U1 (de) | 2000-06-27 | 2005-08-04 | Laboratorios S.A.L.V.A.T., S.A., Esplugues De Llobregat | Von Arylalkylaminen abgeleitete Carbamate |
-
1999
- 1999-06-04 GB GBGB9913083.3A patent/GB9913083D0/en not_active Ceased
-
2000
- 2000-05-10 TW TW089108928A patent/TWI253447B/zh not_active IP Right Cessation
- 2000-05-26 MY MYPI20002328A patent/MY126951A/en unknown
- 2000-05-29 CO CO00039577A patent/CO5170518A1/es active IP Right Grant
- 2000-06-01 AR ARP000102709A patent/AR035548A1/es active IP Right Grant
- 2000-06-02 WO PCT/EP2000/005058 patent/WO2000075114A1/en active IP Right Grant
- 2000-06-02 TR TR2001/03497T patent/TR200103497T2/xx unknown
- 2000-06-02 CZ CZ20014301A patent/CZ302403B6/cs not_active IP Right Cessation
- 2000-06-02 IL IL14657800A patent/IL146578A0/xx active IP Right Grant
- 2000-06-02 PL PL352100A patent/PL198847B1/pl unknown
- 2000-06-02 JP JP2001501595A patent/JP3785365B2/ja not_active Expired - Lifetime
- 2000-06-02 BR BRPI0011324A patent/BRPI0011324B8/pt not_active IP Right Cessation
- 2000-06-02 NZ NZ515669A patent/NZ515669A/xx not_active IP Right Cessation
- 2000-06-02 DE DE201012000009 patent/DE122010000009I2/de active Active
- 2000-06-02 US US10/009,008 patent/US6878721B1/en not_active Expired - Lifetime
- 2000-06-02 ES ES00935163T patent/ES2331457T3/es not_active Expired - Lifetime
- 2000-06-02 PE PE2000000548A patent/PE20010219A1/es not_active IP Right Cessation
- 2000-06-02 CN CNB008084874A patent/CN1156451C/zh not_active Expired - Lifetime
- 2000-06-02 DK DK08171523.7T patent/DK2332915T3/da active
- 2000-06-02 ES ES08171523T patent/ES2402535T3/es not_active Expired - Lifetime
- 2000-06-02 MX MXPA01012474A patent/MXPA01012474A/es active IP Right Grant
- 2000-06-02 EP EP08171523A patent/EP2332915B1/en not_active Expired - Lifetime
- 2000-06-02 HU HU0201658A patent/HU227034B1/hu active Protection Beyond IP Right Term
- 2000-06-02 PT PT00935163T patent/PT1183240E/pt unknown
- 2000-06-02 DE DE60042781T patent/DE60042781D1/de not_active Expired - Lifetime
- 2000-06-02 AU AU50745/00A patent/AU765919B2/en not_active Expired
- 2000-06-02 AT AT00935163T patent/ATE440083T1/de active
- 2000-06-02 DK DK00935163T patent/DK1183240T3/da active
- 2000-06-02 RU RU2001135801/04A patent/RU2244709C2/ru active Protection Beyond IP Right Term
- 2000-06-02 KR KR1020017015568A patent/KR100718615B1/ko not_active Expired - Lifetime
- 2000-06-02 EP EP00935163A patent/EP1183240B1/en not_active Expired - Lifetime
- 2000-06-02 PT PT81715237T patent/PT2332915E/pt unknown
- 2000-06-02 CA CA2375810A patent/CA2375810C/en not_active Expired - Lifetime
- 2000-06-02 HK HK02105569.8A patent/HK1045837B/en not_active IP Right Cessation
- 2000-06-02 SI SI200031045T patent/SI1183240T1/sl unknown
- 2000-06-02 SK SK1743-2001A patent/SK287260B6/sk not_active IP Right Cessation
-
2001
- 2001-11-19 IL IL146578A patent/IL146578A/en active Protection Beyond IP Right Term
- 2001-12-03 NO NO20015912A patent/NO322944B1/no not_active IP Right Cessation
- 2001-12-03 ZA ZA200109931A patent/ZA200109931B/en unknown
-
2005
- 2005-03-07 US US11/074,400 patent/US7622483B2/en not_active Expired - Lifetime
-
2009
- 2009-10-13 US US12/577,855 patent/US7820694B2/en not_active Expired - Fee Related
- 2009-11-11 CY CY20091101179T patent/CY1109604T1/el unknown
-
2010
- 2010-02-15 FR FR10C0006C patent/FR10C0006I2/fr active Active
- 2010-02-17 LU LU91651C patent/LU91651I2/fr unknown
- 2010-02-18 NL NL300437C patent/NL300437I1/nl unknown
- 2010-02-24 BE BE2010C011C patent/BE2010C011I2/fr unknown
- 2010-03-09 CY CY2010003C patent/CY2010003I2/el unknown
- 2010-07-02 NO NO2010014C patent/NO2010014I1/no unknown
- 2010-09-20 US US12/885,922 patent/US8067437B2/en not_active Expired - Fee Related
-
2011
- 2011-11-14 US US13/295,426 patent/US8283362B2/en not_active Expired - Fee Related
-
2012
- 2012-07-23 US US13/555,536 patent/US8436017B2/en not_active Expired - Fee Related
-
2013
- 2013-04-08 US US13/858,308 patent/US8658673B2/en not_active Expired - Fee Related
- 2013-05-24 CY CY20131100413T patent/CY1114120T1/el unknown
- 2013-11-11 US US14/076,478 patent/US8796307B2/en not_active Expired - Fee Related
-
2014
- 2014-08-04 US US14/450,692 patent/US9040559B2/en not_active Expired - Fee Related
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
ES2331457T3 (es) | Agonistas de beta2-adrenoceptor. | |
HK1154584B (en) | Beta2-adrenoceptor agonists | |
EP1407769A1 (en) | Indole derivatives as beta-2 agonists | |
HK1096379A1 (zh) | 用於治疗疾病的磺酰胺衍生物 | |
HK1096379B (en) | Sulfonamide derivatives for the treatment of diseases |