ES2291733T3 - Compuestos de ariletanolamina medicinales. - Google Patents
Compuestos de ariletanolamina medicinales. Download PDFInfo
- Publication number
- ES2291733T3 ES2291733T3 ES03795793T ES03795793T ES2291733T3 ES 2291733 T3 ES2291733 T3 ES 2291733T3 ES 03795793 T ES03795793 T ES 03795793T ES 03795793 T ES03795793 T ES 03795793T ES 2291733 T3 ES2291733 T3 ES 2291733T3
- Authority
- ES
- Spain
- Prior art keywords
- ethyl
- benzodioxin
- methyl
- dihydro
- alkyl
- 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
- 150000001875 compounds Chemical class 0.000 title claims abstract description 258
- 239000001257 hydrogen Substances 0.000 claims abstract description 68
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 68
- 150000003839 salts Chemical class 0.000 claims abstract description 60
- 239000012453 solvate Substances 0.000 claims abstract description 47
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 41
- 150000002367 halogens Chemical group 0.000 claims abstract description 41
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 35
- 125000003118 aryl group Chemical group 0.000 claims abstract description 25
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 24
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 18
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 9
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims abstract description 4
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims abstract description 4
- 125000001624 naphthyl group Chemical group 0.000 claims abstract description 4
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 125000001424 substituent group Chemical group 0.000 claims abstract description 3
- 150000002431 hydrogen Chemical group 0.000 claims abstract 16
- 239000000203 mixture Substances 0.000 claims description 92
- -1 SR 14 Chemical compound 0.000 claims description 89
- 125000000217 alkyl group Chemical group 0.000 claims description 83
- 238000000034 method Methods 0.000 claims description 79
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 39
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 30
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
- 238000006243 chemical reaction Methods 0.000 claims description 26
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 26
- PIGFYZPCRLYGLF-UHFFFAOYSA-N Aluminum nitride Chemical compound [Al]#N PIGFYZPCRLYGLF-UHFFFAOYSA-N 0.000 claims description 24
- 125000006239 protecting group Chemical group 0.000 claims description 20
- CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 19
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 17
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 238000011282 treatment Methods 0.000 claims description 14
- 125000001188 haloalkyl group Chemical group 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 12
- 239000003814 drug Substances 0.000 claims description 11
- 238000011321 prophylaxis Methods 0.000 claims description 11
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 10
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical compound NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 10
- 125000001072 heteroaryl group Chemical group 0.000 claims description 9
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 9
- 230000001012 protector Effects 0.000 claims description 8
- 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 claims description 7
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 7
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 7
- 230000001225 therapeutic effect Effects 0.000 claims description 7
- 239000000048 adrenergic agonist Substances 0.000 claims description 6
- 229940126157 adrenergic receptor agonist Drugs 0.000 claims description 6
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 6
- 239000004615 ingredient Substances 0.000 claims description 6
- 239000008194 pharmaceutical composition Substances 0.000 claims description 6
- 239000000047 product Substances 0.000 claims description 6
- 125000003342 alkenyl group Chemical group 0.000 claims description 5
- 230000001681 protective effect Effects 0.000 claims description 5
- 229920006395 saturated elastomer Polymers 0.000 claims description 5
- VSVNCOSQAVVWAE-YMINUMGASA-N 2-(hydroxymethyl)-4-[(1r)-1-hydroxy-2-[2-[(3r)-3-(1-phenylethoxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]ethyl]phenol Chemical compound C1([C@@H](O)CNCCC2=CC=C3OC[C@H](OC3=C2)COC(C)C=2C=CC=CC=2)=CC=C(O)C(CO)=C1 VSVNCOSQAVVWAE-YMINUMGASA-N 0.000 claims description 4
- DTORYSDPBVKPCI-BVAGGSTKSA-N 2-(hydroxymethyl)-4-[(1r)-1-hydroxy-2-[2-[(3r)-3-[(3-methylsulfonylphenyl)methoxymethyl]-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]ethyl]phenol Chemical compound CS(=O)(=O)C1=CC=CC(COC[C@H]2OC3=CC(CCNC[C@H](O)C=4C=C(CO)C(O)=CC=4)=CC=C3OC2)=C1 DTORYSDPBVKPCI-BVAGGSTKSA-N 0.000 claims description 4
- UOYZKGZGKHEACD-QPPBQGQZSA-N 2-fluoro-4-[(1r)-1-hydroxy-2-[2-[(3r)-3-(phenylmethoxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]ethyl]phenol Chemical compound C([C@@H]1COC2=CC=C(C=C2O1)CCNC[C@H](O)C=1C=C(F)C(O)=CC=1)OCC1=CC=CC=C1 UOYZKGZGKHEACD-QPPBQGQZSA-N 0.000 claims description 4
- BQPPGLWIIUGNKB-NOZRDPDXSA-N 4-[(1r)-1-hydroxy-2-[2-[(3r)-3-(phenylmethoxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]ethyl]-3-methylphenol Chemical compound CC1=CC(O)=CC=C1[C@@H](O)CNCCC1=CC=C(OC[C@@H](COCC=2C=CC=CC=2)O2)C2=C1 BQPPGLWIIUGNKB-NOZRDPDXSA-N 0.000 claims description 4
- LGKNRGURKRQRRL-NOZRDPDXSA-N 4-[(1r)-2-[2-[(3r)-3-[(4-chlorophenyl)methoxymethyl]-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol Chemical compound C1=C(O)C(CO)=CC([C@@H](O)CNCCC=2C=C3O[C@H](COCC=4C=CC(Cl)=CC=4)COC3=CC=2)=C1 LGKNRGURKRQRRL-NOZRDPDXSA-N 0.000 claims description 4
- XEYZFUOKQKMSPH-NOZRDPDXSA-N 4-[(1r)-2-[2-[(3r)-3-[(4-fluorophenyl)methoxymethyl]-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol Chemical compound C1=C(O)C(CO)=CC([C@@H](O)CNCCC=2C=C3O[C@H](COCC=4C=CC(F)=CC=4)COC3=CC=2)=C1 XEYZFUOKQKMSPH-NOZRDPDXSA-N 0.000 claims description 4
- 125000004432 carbon atom Chemical group C* 0.000 claims description 4
- 238000010511 deprotection reaction Methods 0.000 claims description 4
- 125000004438 haloalkoxy group Chemical group 0.000 claims description 4
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
- 238000004519 manufacturing process Methods 0.000 claims description 4
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 4
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 4
- 238000000926 separation method Methods 0.000 claims description 4
- IWSPKHYWOOYAOU-OFNKIYASSA-N (1r)-1-(4-amino-3,5-dichlorophenyl)-2-[2-[(3r)-3-(phenylmethoxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]ethanol Chemical compound C1=C(Cl)C(N)=C(Cl)C=C1[C@@H](O)CNCCC1=CC=C(OC[C@@H](COCC=2C=CC=CC=2)O2)C2=C1 IWSPKHYWOOYAOU-OFNKIYASSA-N 0.000 claims description 3
- SZPCELKEIZHWFO-CGHJUBPDSA-N 2-(hydroxymethyl)-6-[1-hydroxy-2-[2-[(3r)-3-(phenylmethoxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]ethyl]pyridin-3-ol Chemical compound C1=C(O)C(CO)=NC(C(O)CNCCC=2C=C3O[C@H](COCC=4C=CC=CC=4)COC3=CC=2)=C1 SZPCELKEIZHWFO-CGHJUBPDSA-N 0.000 claims description 3
- GNOUEFPUIBRVPP-NLFFAJNJSA-N 4-[(1r)-2-[2-[(3r)-3-[(2,6-dichlorophenyl)methoxymethyl]-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol Chemical compound C1=C(O)C(CO)=CC([C@@H](O)CNCCC=2C=C3O[C@H](COCC=4C(=CC=CC=4Cl)Cl)COC3=CC=2)=C1 GNOUEFPUIBRVPP-NLFFAJNJSA-N 0.000 claims description 3
- RFGYBENEOUTBJN-NOZRDPDXSA-N [3-[[(3r)-6-[2-[[(2r)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]ethyl]-2,3-dihydro-1,4-benzodioxin-3-yl]methoxymethyl]phenyl]urea Chemical compound NC(=O)NC1=CC=CC(COC[C@H]2OC3=CC(CCNC[C@H](O)C=4C=C(CO)C(O)=CC=4)=CC=C3OC2)=C1 RFGYBENEOUTBJN-NOZRDPDXSA-N 0.000 claims description 3
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 3
- 239000013067 intermediate product Substances 0.000 claims description 3
- TVAKVBAPSAPQNU-RDGATRHJSA-N n-[2-hydroxy-5-[(1r)-1-hydroxy-2-[2-[(3r)-3-(phenylmethoxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]ethyl]phenyl]methanesulfonamide Chemical compound C1=C(O)C(NS(=O)(=O)C)=CC([C@@H](O)CNCCC=2C=C3O[C@H](COCC=4C=CC=CC=4)COC3=CC=2)=C1 TVAKVBAPSAPQNU-RDGATRHJSA-N 0.000 claims description 3
- 125000006590 (C2-C6) alkenylene group Chemical group 0.000 claims description 2
- KAHONMCTSMKOLY-NOZRDPDXSA-N 2-(hydroxymethyl)-4-[(1r)-1-hydroxy-2-[2-[(3r)-3-(phenylmethoxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]ethyl]phenol Chemical compound C1=C(O)C(CO)=CC([C@@H](O)CNCCC=2C=C3O[C@H](COCC=4C=CC=CC=4)COC3=CC=2)=C1 KAHONMCTSMKOLY-NOZRDPDXSA-N 0.000 claims description 2
- GXQPBAUTCSQSIT-IMDOIRSXSA-N 2-(hydroxymethyl)-4-[(1r)-1-hydroxy-2-[2-[(3r)-3-[[5-(4-methylsulfinylphenyl)pyridin-3-yl]methoxymethyl]-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]ethyl]phenol Chemical compound C1=CC(S(=O)C)=CC=C1C1=CN=CC(COC[C@H]2OC3=CC(CCNC[C@H](O)C=4C=C(CO)C(O)=CC=4)=CC=C3OC2)=C1 GXQPBAUTCSQSIT-IMDOIRSXSA-N 0.000 claims description 2
- KAHONMCTSMKOLY-ZCYQVOJMSA-N 2-(hydroxymethyl)-4-[(1r)-1-hydroxy-2-[2-[(3s)-3-(phenylmethoxymethyl)-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]ethyl]phenol Chemical compound C1=C(O)C(CO)=CC([C@@H](O)CNCCC=2C=C3O[C@@H](COCC=4C=CC=CC=4)COC3=CC=2)=C1 KAHONMCTSMKOLY-ZCYQVOJMSA-N 0.000 claims description 2
- VCWVPIIXFQFBHP-RDGATRHJSA-N 3-[[(3r)-6-[2-[[(2r)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]ethyl]-2,3-dihydro-1,4-benzodioxin-3-yl]methoxymethyl]benzenesulfonamide Chemical compound NS(=O)(=O)C1=CC=CC(COC[C@H]2OC3=CC(CCNC[C@H](O)C=4C=C(CO)C(O)=CC=4)=CC=C3OC2)=C1 VCWVPIIXFQFBHP-RDGATRHJSA-N 0.000 claims description 2
- ZGYJBLHKCAJDIX-RSXGOPAZSA-N 3-[[(3r)-6-[2-[[(2r)-2-hydroxy-2-[4-hydroxy-3-(hydroxymethyl)phenyl]ethyl]amino]ethyl]-2,3-dihydro-1,4-benzodioxin-3-yl]methoxymethyl]benzonitrile Chemical compound C1=C(O)C(CO)=CC([C@@H](O)CNCCC=2C=C3O[C@H](COCC=4C=C(C=CC=4)C#N)COC3=CC=2)=C1 ZGYJBLHKCAJDIX-RSXGOPAZSA-N 0.000 claims description 2
- XVFVDBAZXYZAKW-IRLDBZIGSA-N 4-[(1r)-2-[2-[(3r)-3-[(2,6-dichloropyridin-3-yl)methoxymethyl]-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol Chemical compound C1=C(O)C(CO)=CC([C@@H](O)CNCCC=2C=C3O[C@H](COCC=4C(=NC(Cl)=CC=4)Cl)COC3=CC=2)=C1 XVFVDBAZXYZAKW-IRLDBZIGSA-N 0.000 claims description 2
- VQGKMDUXRXRKAR-VIZCGCQYSA-N 4-[(1r)-2-[2-[(3r)-3-[(3-cyclopentylsulfanylphenyl)methoxymethyl]-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol Chemical compound C1=C(O)C(CO)=CC([C@@H](O)CNCCC=2C=C3O[C@H](COCC=4C=C(SC5CCCC5)C=CC=4)COC3=CC=2)=C1 VQGKMDUXRXRKAR-VIZCGCQYSA-N 0.000 claims description 2
- UYFAWFCRMQTTTL-VIZCGCQYSA-N 4-[(1r)-2-[2-[(3r)-3-[(3-cyclopentylsulfonylphenyl)methoxymethyl]-2,3-dihydro-1,4-benzodioxin-6-yl]ethylamino]-1-hydroxyethyl]-2-(hydroxymethyl)phenol Chemical compound C1=C(O)C(CO)=CC([C@@H](O)CNCCC=2C=C3O[C@H](COCC=4C=C(C=CC=4)S(=O)(=O)C4CCCC4)COC3=CC=2)=C1 UYFAWFCRMQTTTL-VIZCGCQYSA-N 0.000 claims description 2
- 230000029936 alkylation Effects 0.000 claims description 2
- 238000005804 alkylation reaction Methods 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 125000004104 aryloxy group Chemical group 0.000 claims description 2
- 125000004429 atom Chemical group 0.000 claims description 2
- 239000003937 drug carrier Substances 0.000 claims description 2
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims description 2
- 125000000623 heterocyclic group Chemical group 0.000 claims description 2
- WJRBRSLFGCUECM-UHFFFAOYSA-N hydantoin Chemical compound O=C1CNC(=O)N1 WJRBRSLFGCUECM-UHFFFAOYSA-N 0.000 claims description 2
- 125000002632 imidazolidinyl group Chemical group 0.000 claims description 2
- 238000013160 medical therapy Methods 0.000 claims description 2
- COWNFYYYZFRNOY-UHFFFAOYSA-N oxazolidinedione Chemical compound O=C1COC(=O)N1 COWNFYYYZFRNOY-UHFFFAOYSA-N 0.000 claims description 2
- 125000000160 oxazolidinyl group Chemical group 0.000 claims description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 5
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 abstract 1
- 125000001475 halogen functional group Chemical group 0.000 abstract 1
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 100
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 84
- 239000000243 solution Substances 0.000 description 84
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 65
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 61
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 56
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 49
- 239000002904 solvent Substances 0.000 description 42
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 36
- 239000000377 silicon dioxide Substances 0.000 description 36
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 31
- 235000019439 ethyl acetate Nutrition 0.000 description 29
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 description 27
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 description 27
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 26
- 239000000284 extract Substances 0.000 description 24
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 22
- 239000002253 acid Substances 0.000 description 21
- 239000002585 base Substances 0.000 description 21
- 238000009472 formulation Methods 0.000 description 20
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000003921 oil Substances 0.000 description 16
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 239000012044 organic layer Substances 0.000 description 14
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 13
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- 239000012299 nitrogen atmosphere Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 11
- 230000015572 biosynthetic process Effects 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
- 239000012267 brine Substances 0.000 description 10
- 239000003795 chemical substances by application Substances 0.000 description 10
- HJORMJIFDVBMOB-UHFFFAOYSA-N rolipram Chemical compound COC1=CC=C(C2CC(=O)NC2)C=C1OC1CCCC1 HJORMJIFDVBMOB-UHFFFAOYSA-N 0.000 description 10
- 229950005741 rolipram Drugs 0.000 description 10
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
- 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 10
- 239000005557 antagonist Substances 0.000 description 9
- 210000004027 cell Anatomy 0.000 description 9
- 238000004440 column chromatography Methods 0.000 description 9
- WACQKHWOTAEEFS-UHFFFAOYSA-N cyclohexane;ethyl acetate Chemical compound CCOC(C)=O.C1CCCCC1 WACQKHWOTAEEFS-UHFFFAOYSA-N 0.000 description 9
- 238000004128 high performance liquid chromatography Methods 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 239000011734 sodium Substances 0.000 description 9
- 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 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 108010014499 beta-2 Adrenergic Receptors Proteins 0.000 description 8
- 102000016966 beta-2 Adrenergic Receptors Human genes 0.000 description 8
- 229910052799 carbon Inorganic materials 0.000 description 8
- 238000004587 chromatography analysis Methods 0.000 description 8
- 150000002148 esters Chemical class 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 8
- 239000002245 particle Substances 0.000 description 8
- 230000001175 peptic effect Effects 0.000 description 8
- 229950010765 pivalate Drugs 0.000 description 8
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 description 8
- 238000002360 preparation method Methods 0.000 description 8
- 102000005962 receptors Human genes 0.000 description 8
- 108020003175 receptors Proteins 0.000 description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 7
- 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 7
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
- 239000000556 agonist Substances 0.000 description 7
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Classifications
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- 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
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/10—1,4-Dioxanes; Hydrogenated 1,4-dioxanes
- C07D319/14—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems
- C07D319/16—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D319/20—1,4-Dioxanes; Hydrogenated 1,4-dioxanes condensed with carbocyclic rings or ring systems condensed with one six-membered ring with substituents attached to the hetero ring
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
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- Endocrinology (AREA)
- Cardiology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Urology & Nephrology (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)
- Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB0224494A GB0224494D0 (en) | 2002-10-22 | 2002-10-22 | Medicinal compounds |
| GB0224498A GB0224498D0 (en) | 2002-10-22 | 2002-10-22 | Medicinal compounds |
| GB0224498 | 2002-10-22 | ||
| GB0224494 | 2002-10-22 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2291733T3 true ES2291733T3 (es) | 2008-03-01 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| ES03795793T Expired - Lifetime ES2291733T3 (es) | 2002-10-22 | 2003-10-20 | Compuestos de ariletanolamina medicinales. |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US20060205790A1 (enExample) |
| EP (1) | EP1554264B1 (enExample) |
| JP (1) | JP2006506373A (enExample) |
| AT (1) | ATE369353T1 (enExample) |
| AU (1) | AU2003298094A1 (enExample) |
| DE (1) | DE60315492T2 (enExample) |
| ES (1) | ES2291733T3 (enExample) |
| WO (1) | WO2004037807A2 (enExample) |
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| GB0411056D0 (en) | 2004-05-18 | 2004-06-23 | Novartis Ag | Organic compounds |
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| GB0418045D0 (en) | 2004-08-12 | 2004-09-15 | Glaxo Group Ltd | Compounds |
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| GB201706102D0 (en) | 2017-04-18 | 2017-05-31 | Glaxosmithkline Ip Dev Ltd | Chemical compounds |
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| US2918408A (en) * | 1957-04-08 | 1959-12-22 | Lakeside Lab Inc | Anti-spasmodic compositions specific for treating spasm of the colon |
| JPS55124742A (en) * | 1979-03-20 | 1980-09-26 | Kyowa Hakko Kogyo Co Ltd | Novel aminoalcohol derivative |
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| US4778054A (en) * | 1982-10-08 | 1988-10-18 | Glaxo Group Limited | Pack for administering medicaments to patients |
| GB8310477D0 (en) * | 1983-04-18 | 1983-05-25 | Glaxo Group Ltd | Chemical compounds |
| GB8409909D0 (en) * | 1984-04-17 | 1984-05-31 | Glaxo Group Ltd | Chemical compounds |
| DK163640C (da) * | 1985-07-30 | 1992-08-17 | Glaxo Group Ltd | Apparat til administrering af medikamenter |
| GB9004781D0 (en) * | 1990-03-02 | 1990-04-25 | Glaxo Group Ltd | Device |
| WO1993019749A1 (en) * | 1992-04-02 | 1993-10-14 | Smithkline Beecham Corporation | Compounds useful for treating allergic and inflammatory diseases |
| US5998428A (en) * | 1995-05-31 | 1999-12-07 | Smithkline Beecham Corporation | Compounds and methods for treating PDE IV-related diseases |
| JPH10152460A (ja) * | 1996-11-21 | 1998-06-09 | Kissei Pharmaceut Co Ltd | ２−アミノ−１−（４−ヒドロキシ−２−メチルフェニル）プロパノール誘導体 |
| IL129715A0 (en) * | 1996-12-30 | 2000-02-29 | American Home Prod | Substituted benzo (1,4) dioxanes as antiobesity agents |
| GB9700226D0 (en) * | 1997-01-08 | 1997-02-26 | Glaxo Group Ltd | Inhalation device |
| WO2002070490A1 (en) * | 2001-03-08 | 2002-09-12 | Glaxo Group Limited | Agonists of beta-adrenoceptors |
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- 2003-10-20 WO PCT/EP2003/011648 patent/WO2004037807A2/en not_active Ceased
- 2003-10-20 US US10/532,467 patent/US20060205790A1/en not_active Abandoned
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- 2003-10-20 EP EP03795793A patent/EP1554264B1/en not_active Expired - Lifetime
- 2003-10-20 JP JP2004545914A patent/JP2006506373A/ja active Pending
- 2003-10-20 ES ES03795793T patent/ES2291733T3/es not_active Expired - Lifetime
Also Published As
| Publication number | Publication date |
|---|---|
| EP1554264B1 (en) | 2007-08-08 |
| WO2004037807A9 (en) | 2004-08-19 |
| JP2006506373A (ja) | 2006-02-23 |
| ATE369353T1 (de) | 2007-08-15 |
| WO2004037807A2 (en) | 2004-05-06 |
| US20060205790A1 (en) | 2006-09-14 |
| DE60315492T2 (de) | 2008-04-24 |
| AU2003298094A1 (en) | 2004-05-13 |
| WO2004037807A3 (en) | 2004-06-24 |
| DE60315492D1 (de) | 2007-09-20 |
| EP1554264A2 (en) | 2005-07-20 |
| AU2003298094A8 (en) | 2004-05-13 |
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