JP2011505343A5

JP2011505343A5 -

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Publication number: JP2011505343A5
Authority: JP; Japan
Prior art keywords: mmol; phenyl; ethyl; title compound; adamantyl
Prior art date: 2008-11-10
Legal status : Pending

Application number

JP2010535263A

Other languages

English (en)

Japanese (ja)

Other versions

JP2011505343A (ja

Filing date

2008-11-10

Publication date

2011-11-10

2007-11-28 Priority claimed from ES200703157A external-priority patent/ES2320961B1/es

2008-11-10 Application filed filed Critical

2011-02-24 Publication of JP2011505343A publication Critical patent/JP2011505343A/ja

2011-11-10 Publication of JP2011505343A5 publication Critical patent/JP2011505343A5/ja

Status Pending legal-status Critical Current

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239000000543 intermediate Substances 0.000 description 256
150000001875 compounds Chemical class 0.000 description 170
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 165
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 159
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 99
239000000203 mixture Substances 0.000 description 92
239000000243 solution Substances 0.000 description 88
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 81
238000000034 method Methods 0.000 description 76
239000002904 solvent Substances 0.000 description 76
239000013058 crude material Substances 0.000 description 68
239000007787 solid Substances 0.000 description 62
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 60
230000002829 reductive effect Effects 0.000 description 60
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 50
239000000741 silica gel Substances 0.000 description 46
229910002027 silica gel Inorganic materials 0.000 description 46
FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 45
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 44
238000000746 purification Methods 0.000 description 43
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 42
238000004440 column chromatography Methods 0.000 description 41
-1 1-adamantyl Chemical group 0.000 description 39
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 37
239000011541 reaction mixture Substances 0.000 description 37
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 33
239000012044 organic layer Substances 0.000 description 31
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
239000003921 oil Substances 0.000 description 27
150000003839 salts Chemical class 0.000 description 27
235000019198 oils Nutrition 0.000 description 26
VEPTXBCIDSFGBF-UHFFFAOYSA-M tetrabutylazanium;fluoride;trihydrate Chemical compound O.O.O.[F-].CCCC[N+](CCCC)(CCCC)CCCC VEPTXBCIDSFGBF-UHFFFAOYSA-M 0.000 description 26
235000017557 sodium bicarbonate Nutrition 0.000 description 25
229910000030 sodium bicarbonate Inorganic materials 0.000 description 25
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 24
230000035484 reaction time Effects 0.000 description 24
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 24
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 22
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 20
238000009472 formulation Methods 0.000 description 20
238000012360 testing method Methods 0.000 description 19
238000005160 1H NMR spectroscopy Methods 0.000 description 18
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 18
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
239000002775 capsule Substances 0.000 description 18
201000010099 disease Diseases 0.000 description 18
230000000694 effects Effects 0.000 description 18
238000011282 treatment Methods 0.000 description 17
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
239000000843 powder Substances 0.000 description 16
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 15
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 15
229910000041 hydrogen chloride Inorganic materials 0.000 description 15
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 15
235000009518 sodium iodide Nutrition 0.000 description 15
102000016966 beta-2 Adrenergic Receptors Human genes 0.000 description 14
108010014499 beta-2 Adrenergic Receptors Proteins 0.000 description 14
125000004432 carbon atom Chemical group C* 0.000 description 14
239000003814 drug Substances 0.000 description 14
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 13
229910052799 carbon Inorganic materials 0.000 description 12
238000006243 chemical reaction Methods 0.000 description 12
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
125000006239 protecting group Chemical group 0.000 description 12
239000004480 active ingredient Substances 0.000 description 11
239000008194 pharmaceutical composition Substances 0.000 description 11
229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 10
239000000443 aerosol Substances 0.000 description 10
125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 10
239000003246 corticosteroid Substances 0.000 description 10
239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 10
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 10
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
239000013543 active substance Substances 0.000 description 9
239000012267 brine Substances 0.000 description 9
239000003054 catalyst Substances 0.000 description 9
238000005259 measurement Methods 0.000 description 9
239000002245 particle Substances 0.000 description 9
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 8
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 8
229910000024 caesium carbonate Inorganic materials 0.000 description 8
238000001914 filtration Methods 0.000 description 8
239000012453 solvate Substances 0.000 description 8
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 8
JQJUYDQHSZTDDO-NRFANRHFSA-N 5-[(1r)-2-bromo-1-[tert-butyl(dimethyl)silyl]oxyethyl]-8-phenylmethoxy-1h-quinolin-2-one Chemical compound C1=2NC(=O)C=CC=2C([C@H](CBr)O[Si](C)(C)C(C)(C)C)=CC=C1OCC1=CC=CC=C1 JQJUYDQHSZTDDO-NRFANRHFSA-N 0.000 description 7
GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 7
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 7
239000000048 adrenergic agonist Substances 0.000 description 7
229940126157 adrenergic receptor agonist Drugs 0.000 description 7
150000001412 amines Chemical class 0.000 description 7
208000006673 asthma Diseases 0.000 description 7
229940079593 drug Drugs 0.000 description 7
239000006260 foam Substances 0.000 description 7
125000004435 hydrogen atom Chemical group [H]* 0.000 description 7
239000007788 liquid Substances 0.000 description 7
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
229960002744 mometasone furoate Drugs 0.000 description 7
WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 description 7
239000002244 precipitate Substances 0.000 description 7
238000002360 preparation method Methods 0.000 description 7
239000000725 suspension Substances 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 6
208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 6
241000124008 Mammalia Species 0.000 description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 6
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 6
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
239000000812 cholinergic antagonist Substances 0.000 description 6
238000002474 experimental method Methods 0.000 description 6
229960000289 fluticasone propionate Drugs 0.000 description 6
WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate 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)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 6
239000007903 gelatin capsule Substances 0.000 description 6
239000008101 lactose Substances 0.000 description 6
229960001375 lactose Drugs 0.000 description 6
229910052757 nitrogen Inorganic materials 0.000 description 6
239000000546 pharmaceutical excipient Substances 0.000 description 6
229910000027 potassium carbonate Inorganic materials 0.000 description 6
239000012312 sodium hydride Substances 0.000 description 6
229910000104 sodium hydride Inorganic materials 0.000 description 6
239000003826 tablet Substances 0.000 description 6
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 5
241000700198 Cavia Species 0.000 description 5
LUKZNWIVRBCLON-GXOBDPJESA-N Ciclesonide Chemical compound C1([C@H]2O[C@@]3([C@H](O2)C[C@@H]2[C@@]3(C[C@H](O)[C@@H]3[C@@]4(C)C=CC(=O)C=C4CC[C@H]32)C)C(=O)COC(=O)C(C)C)CCCCC1 LUKZNWIVRBCLON-GXOBDPJESA-N 0.000 description 5
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
208000010412 Glaucoma Diseases 0.000 description 5
208000019693 Lung disease Diseases 0.000 description 5
229940124748 beta 2 agonist Drugs 0.000 description 5
229960004436 budesonide Drugs 0.000 description 5
229960003728 ciclesonide Drugs 0.000 description 5
XTULMSXFIHGYFS-VLSRWLAYSA-N fluticasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(F)[C@@]4(C)C=CC(=O)C=C4[C@@H](F)C[C@H]3[C@@H]2C[C@H]1C)C(=O)SCF)C(=O)C1=CC=CO1 XTULMSXFIHGYFS-VLSRWLAYSA-N 0.000 description 5
229960001469 fluticasone furoate Drugs 0.000 description 5
239000003380 propellant Substances 0.000 description 5
229940124597 therapeutic agent Drugs 0.000 description 5
JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 4
SJJCQDRGABAVBB-UHFFFAOYSA-N 1-hydroxy-2-naphthoic acid Chemical compound C1=CC=CC2=C(O)C(C(=O)O)=CC=C21 SJJCQDRGABAVBB-UHFFFAOYSA-N 0.000 description 4
IAVREABSGIHHMO-UHFFFAOYSA-N 3-hydroxybenzaldehyde Chemical compound OC1=CC=CC(C=O)=C1 IAVREABSGIHHMO-UHFFFAOYSA-N 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 description 4
206010061218 Inflammation Diseases 0.000 description 4
241001465754 Metazoa Species 0.000 description 4
229940121948 Muscarinic receptor antagonist Drugs 0.000 description 4
208000012902 Nervous system disease Diseases 0.000 description 4
ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 4
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
ANGKOCUUWGHLCE-HKUYNNGSSA-N [(3s)-1,1-dimethylpyrrolidin-1-ium-3-yl] (2r)-2-cyclopentyl-2-hydroxy-2-phenylacetate Chemical class C1[N+](C)(C)CC[C@@H]1OC(=O)[C@](O)(C=1C=CC=CC=1)C1CCCC1 ANGKOCUUWGHLCE-HKUYNNGSSA-N 0.000 description 4
ASMXXROZKSBQIH-UHFFFAOYSA-N [1-(3-phenoxypropyl)-1-azoniabicyclo[2.2.2]octan-3-yl] 2-hydroxy-2,2-dithiophen-2-ylacetate Chemical class C=1C=CSC=1C(C=1SC=CC=1)(O)C(=O)OC(C(CC1)CC2)C[N+]21CCCOC1=CC=CC=C1 ASMXXROZKSBQIH-UHFFFAOYSA-N 0.000 description 4
OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 4
229960004373 acetylcholine Drugs 0.000 description 4
230000009471 action Effects 0.000 description 4
125000002252 acyl group Chemical group 0.000 description 4
239000003570 air Substances 0.000 description 4
230000029936 alkylation Effects 0.000 description 4
238000005804 alkylation reaction Methods 0.000 description 4
QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
229910052786 argon Inorganic materials 0.000 description 4
206010006451 bronchitis Diseases 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
239000012230 colorless oil Substances 0.000 description 4
229960001334 corticosteroids Drugs 0.000 description 4
239000003937 drug carrier Substances 0.000 description 4
239000007789 gas Substances 0.000 description 4
208000019622 heart disease Diseases 0.000 description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
230000004054 inflammatory process Effects 0.000 description 4
229960001317 isoprenaline Drugs 0.000 description 4
210000004072 lung Anatomy 0.000 description 4
125000004433 nitrogen atom Chemical group N* 0.000 description 4
102000005962 receptors Human genes 0.000 description 4
108020003175 receptors Proteins 0.000 description 4
238000011084 recovery Methods 0.000 description 4
238000010992 reflux Methods 0.000 description 4
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
LERNTVKEWCAPOY-DZZGSBJMSA-N tiotropium Chemical class 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 description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 4
XLUNGCBILVFOGF-BTYPSACZSA-N 5-[(1r)-2-[1-[4-[2-(1-adamantyl)ethoxy]phenyl]propan-2-ylamino]-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNC(C)CC(C=C1)=CC=C1OCCC1(C2)CC(C3)CC2CC3C1 XLUNGCBILVFOGF-BTYPSACZSA-N 0.000 description 3
RSYITTWHSUDWEQ-RFZIMGSGSA-N 5-[(1r)-2-[2-[3-(1-adamantylmethoxy)phenyl]ethylamino]-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNCCC1=CC=CC(OCC23CC4CC(CC(C4)C2)C3)=C1 RSYITTWHSUDWEQ-RFZIMGSGSA-N 0.000 description 3
UPGBLLQKLWDIPW-YKQFMLTQSA-N 5-[(1r)-2-[2-[3-[2-(1-adamantyl)ethoxy]phenyl]ethylamino]-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CNCCC1=CC=CC(OCCC23CC4CC(CC(C4)C2)C3)=C1 UPGBLLQKLWDIPW-YKQFMLTQSA-N 0.000 description 3
UGMICKAMZZVWIQ-VEHNHPCZSA-N 5-[(1r)-2-[[(2r)-1-[3-[2-(1-adamantyl)ethoxy]phenyl]propan-2-yl]amino]-1-hydroxyethyl]-8-hydroxy-1h-quinolin-2-one Chemical compound N1C(=O)C=CC2=C1C(O)=CC=C2[C@@H](O)CN[C@H](C)CC1=CC=CC(OCCC23CC4CC(CC(C4)C2)C3)=C1 UGMICKAMZZVWIQ-VEHNHPCZSA-N 0.000 description 3
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 3
USFZMSVCRYTOJT-UHFFFAOYSA-N Ammonium acetate Chemical compound N.CC(O)=O USFZMSVCRYTOJT-UHFFFAOYSA-N 0.000 description 3
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206010006458 Bronchitis chronic Diseases 0.000 description 3
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208000020446 Cardiac disease Diseases 0.000 description 3
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 3
206010014561 Emphysema Diseases 0.000 description 3
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208000005107 Premature Birth Diseases 0.000 description 3
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
239000000556 agonist Substances 0.000 description 3
125000000217 alkyl group Chemical group 0.000 description 3
229940043376 ammonium acetate Drugs 0.000 description 3
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QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
230000000178 bronchoprotective effect Effects 0.000 description 3
239000000969 carrier Substances 0.000 description 3
208000007451 chronic 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
238000010511 deprotection reaction Methods 0.000 description 3
229960003957 dexamethasone Drugs 0.000 description 3
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239000012153 distilled water Substances 0.000 description 3
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JP2010535263A 2007-11-28 2008-11-10 β２アドレナリン受容体のアゴニストとしての４−（２−アミノ−１−ヒドロキシエチル）フェノール誘導体 Pending JP2011505343A (ja)