ES2315425T3 - Compuestos de amonio cuaternario y su uso como agentes antimuscarinicos. - Google Patents
Compuestos de amonio cuaternario y su uso como agentes antimuscarinicos. Download PDFInfo
- Publication number
- ES2315425T3 ES2315425T3 ES02793840T ES02793840T ES2315425T3 ES 2315425 T3 ES2315425 T3 ES 2315425T3 ES 02793840 T ES02793840 T ES 02793840T ES 02793840 T ES02793840 T ES 02793840T ES 2315425 T3 ES2315425 T3 ES 2315425T3
- Authority
- ES
- Spain
- Prior art keywords
- aminium
- diisopropyl
- methyl
- quaternary ammonium
- phenylpropan
- 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
- 150000003856 quaternary ammonium compounds Chemical class 0.000 title claims description 43
- 239000003149 muscarinic antagonist Substances 0.000 title description 8
- -1 compound (3R)-3-[2-hydroxy-5-(trifluoromethyl)phenyl]-N,N-diisopropyl-N-methyl-3-phenylpropan-1-aminium bromide Chemical class 0.000 claims abstract description 58
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 56
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 31
- PESFBMQBUBQIHZ-OAQYLSRUSA-O [(3r)-3-(2-hydroxy-5-methylphenyl)-3-phenylpropyl]-methyl-di(propan-2-yl)azanium Chemical compound C1([C@@H](CC[N+](C)(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 PESFBMQBUBQIHZ-OAQYLSRUSA-O 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 20
- 229910052799 carbon Inorganic materials 0.000 claims description 19
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
- 208000006673 asthma Diseases 0.000 claims description 16
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 14
- 239000003814 drug Substances 0.000 claims description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 13
- 208000036071 Rhinorrhea Diseases 0.000 claims description 12
- 206010039101 Rhinorrhoea Diseases 0.000 claims description 12
- 201000009240 nasopharyngitis Diseases 0.000 claims description 12
- 206010039085 Rhinitis allergic Diseases 0.000 claims description 10
- 239000002253 acid Substances 0.000 claims description 9
- 230000001684 chronic effect Effects 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 8
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 150000001450 anions Chemical class 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 7
- 238000004519 manufacturing process Methods 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 230000000414 obstructive effect Effects 0.000 claims description 6
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 6
- 230000002685 pulmonary effect Effects 0.000 claims description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims description 4
- XCJAYQXUPYJVJF-ZMBIFBSDSA-N [(3r)-3-(2-hydroxy-5-methylphenyl)-3-phenylpropyl]-methyl-di(propan-2-yl)azanium;chloride Chemical compound [Cl-].C1([C@@H](CC[N+](C)(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 XCJAYQXUPYJVJF-ZMBIFBSDSA-N 0.000 claims description 4
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 4
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 claims description 3
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 3
- 150000007513 acids Chemical class 0.000 claims description 3
- 201000010099 disease Diseases 0.000 claims description 3
- 239000008194 pharmaceutical composition Substances 0.000 claims description 3
- ANOLTRORIAXJDT-UHFFFAOYSA-O 3,3-bis(2-hydroxy-5-methylphenyl)propyl-methyl-di(propan-2-yl)azanium Chemical compound C=1C(C)=CC=C(O)C=1C(CC[N+](C)(C(C)C)C(C)C)C1=CC(C)=CC=C1O ANOLTRORIAXJDT-UHFFFAOYSA-O 0.000 claims description 2
- HEHGHACMSVNGGS-HSZRJFAPSA-O [(3r)-3-(2-hydroxy-5-methylphenyl)-3-phenylpropyl]-di(propan-2-yl)-propylazanium Chemical compound C1([C@@H](CC[N+](CCC)(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 HEHGHACMSVNGGS-HSZRJFAPSA-O 0.000 claims description 2
- PEWRIIPJUZQBRP-HXUWFJFHSA-O [(3r)-3-(5-carbamoyl-2-hydroxyphenyl)-3-phenylpropyl]-methyl-di(propan-2-yl)azanium Chemical compound C1([C@@H](CC[N+](C)(C(C)C)C(C)C)C=2C(=CC=C(C=2)C(N)=O)O)=CC=CC=C1 PEWRIIPJUZQBRP-HXUWFJFHSA-O 0.000 claims description 2
- 150000003868 ammonium compounds Chemical class 0.000 claims description 2
- 229940124531 pharmaceutical excipient Drugs 0.000 claims description 2
- AIWHVYSXHUYYRQ-UHFFFAOYSA-N 3,3-bis(2-methoxyphenyl)propyl-methyl-di(propan-2-yl)azanium Chemical compound COC1=CC=CC=C1C(CC[N+](C)(C(C)C)C(C)C)C1=CC=CC=C1OC AIWHVYSXHUYYRQ-UHFFFAOYSA-N 0.000 claims 1
- WHBXIETUIUWZTC-LJQANCHMSA-O tert-butyl-[(3r)-3-(2-hydroxy-5-methylphenyl)-3-phenylpropyl]-dimethylazanium Chemical compound CC1=CC=C(O)C([C@H](CC[N+](C)(C)C(C)(C)C)C=2C=CC=CC=2)=C1 WHBXIETUIUWZTC-LJQANCHMSA-O 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 abstract description 124
- GZUXJHMPEANEGY-UHFFFAOYSA-N bromomethane Chemical compound BrC GZUXJHMPEANEGY-UHFFFAOYSA-N 0.000 abstract description 6
- 229940102396 methyl bromide Drugs 0.000 abstract description 3
- FIZRZYUJJOUDHY-LJQANCHMSA-N 2-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-(trifluoromethyl)phenol Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C=2)C(F)(F)F)O)=CC=CC=C1 FIZRZYUJJOUDHY-LJQANCHMSA-N 0.000 abstract description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 2
- 241000699670 Mus sp. Species 0.000 description 32
- 238000000034 method Methods 0.000 description 32
- OOGJQPCLVADCPB-HXUWFJFHSA-N tolterodine Chemical compound C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 OOGJQPCLVADCPB-HXUWFJFHSA-N 0.000 description 30
- 238000011282 treatment Methods 0.000 description 30
- 239000000443 aerosol Substances 0.000 description 26
- 229960004045 tolterodine Drugs 0.000 description 25
- BDIAUFOIMFAIPU-UHFFFAOYSA-N valepotriate Natural products CC(C)CC(=O)OC1C=C(C(=COC2OC(=O)CC(C)C)COC(C)=O)C2C11CO1 BDIAUFOIMFAIPU-UHFFFAOYSA-N 0.000 description 25
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 19
- NZWOPGCLSHLLPA-UHFFFAOYSA-N methacholine Chemical compound C[N+](C)(C)CC(C)OC(C)=O NZWOPGCLSHLLPA-UHFFFAOYSA-N 0.000 description 17
- 229960002329 methacholine Drugs 0.000 description 17
- 125000004432 carbon atom Chemical group C* 0.000 description 16
- 239000000243 solution Substances 0.000 description 15
- 230000000694 effects Effects 0.000 description 14
- 125000001424 substituent group Chemical group 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 12
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 150000003839 salts Chemical class 0.000 description 12
- 208000035475 disorder Diseases 0.000 description 10
- 239000001257 hydrogen Substances 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 229910052757 nitrogen Inorganic materials 0.000 description 9
- 206010006482 Bronchospasm Diseases 0.000 description 8
- 206010046543 Urinary incontinence Diseases 0.000 description 8
- 201000010105 allergic rhinitis Diseases 0.000 description 8
- 230000007885 bronchoconstriction Effects 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 125000003118 aryl group Chemical group 0.000 description 7
- 125000004429 atom Chemical group 0.000 description 7
- 239000000460 chlorine Substances 0.000 description 7
- 229960001888 ipratropium Drugs 0.000 description 7
- OEXHQOGQTVQTAT-JRNQLAHRSA-N ipratropium Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)[N@@+]2(C)C(C)C)C(=O)C(CO)C1=CC=CC=C1 OEXHQOGQTVQTAT-JRNQLAHRSA-N 0.000 description 7
- 230000036470 plasma concentration Effects 0.000 description 7
- 230000002485 urinary effect Effects 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- 206010020853 Hypertonic bladder Diseases 0.000 description 6
- 229940124630 bronchodilator Drugs 0.000 description 6
- 239000012458 free base Substances 0.000 description 6
- 150000003242 quaternary ammonium salts Chemical class 0.000 description 6
- 206010039083 rhinitis Diseases 0.000 description 6
- 239000007921 spray Substances 0.000 description 6
- 208000024891 symptom Diseases 0.000 description 6
- 210000003932 urinary bladder Anatomy 0.000 description 6
- NHBKXEKEPDILRR-UHFFFAOYSA-N 2,3-bis(butanoylsulfanyl)propyl butanoate Chemical compound CCCC(=O)OCC(SC(=O)CCC)CSC(=O)CCC NHBKXEKEPDILRR-UHFFFAOYSA-N 0.000 description 5
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 5
- 238000005481 NMR spectroscopy Methods 0.000 description 5
- 208000009722 Overactive Urinary Bladder Diseases 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 238000010586 diagram Methods 0.000 description 5
- 229940079593 drug Drugs 0.000 description 5
- 229960001361 ipratropium bromide Drugs 0.000 description 5
- 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 5
- 239000012071 phase Substances 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 229930003347 Atropine Natural products 0.000 description 4
- 208000000059 Dyspnea Diseases 0.000 description 4
- 206010013975 Dyspnoeas Diseases 0.000 description 4
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 4
- 241000124008 Mammalia Species 0.000 description 4
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 description 4
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 4
- 125000002252 acyl group Chemical group 0.000 description 4
- 229960000396 atropine Drugs 0.000 description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 210000004072 lung Anatomy 0.000 description 4
- 108700025647 major vault Proteins 0.000 description 4
- 239000006199 nebulizer Substances 0.000 description 4
- 239000002244 precipitate Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- 150000003512 tertiary amines Chemical class 0.000 description 4
- KISZTEOELCMZPY-UHFFFAOYSA-N 3,3-diphenylpropylamine Chemical class C=1C=CC=CC=1C(CCN)C1=CC=CC=C1 KISZTEOELCMZPY-UHFFFAOYSA-N 0.000 description 3
- YYSCJLLOWOUSHH-UHFFFAOYSA-N 4,4'-disulfanyldibutanoic acid Chemical compound OC(=O)CCCSSCCCC(O)=O YYSCJLLOWOUSHH-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- 206010021639 Incontinence Diseases 0.000 description 3
- 208000019693 Lung disease Diseases 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 230000009471 action Effects 0.000 description 3
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- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 3
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 3
- 230000001078 anti-cholinergic effect Effects 0.000 description 3
- 230000001022 anti-muscarinic effect Effects 0.000 description 3
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 3
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- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 3
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- 230000005713 exacerbation Effects 0.000 description 3
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- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 3
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- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 3
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 3
- TWHNMSJGYKMTRB-KXYUELECSA-N (2r,3r)-2,3-dihydroxybutanedioic acid;2-[(1r)-3-[di(propan-2-yl)amino]-1-phenylpropyl]-4-methylphenol Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.C1([C@@H](CCN(C(C)C)C(C)C)C=2C(=CC=C(C)C=2)O)=CC=CC=C1 TWHNMSJGYKMTRB-KXYUELECSA-N 0.000 description 2
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- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
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- 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
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/06—Antiasthmatics
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
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- A61P37/00—Drugs for immunological or allergic disorders
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- 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
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- 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
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- 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
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/48—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups
- C07C215/54—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by hydroxy groups linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
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- 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
- C07C215/46—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C215/66—Compounds containing amino and hydroxy groups bound to the same carbon skeleton having hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with quaternised amino groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/54—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C217/56—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms
- C07C217/62—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms linked by carbon chains having at least three carbon atoms between the amino groups and the six-membered aromatic ring or the condensed ring system containing that ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C219/00—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C219/26—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton
- C07C219/28—Compounds containing amino and esterified hydroxy groups bound to the same carbon skeleton having esterified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton having amino groups bound to acyclic carbon atoms of the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/28—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton
- C07C237/30—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atom of at least one of the carboxamide groups bound to a carbon atom of a non-condensed six-membered aromatic ring of the carbon skeleton having the nitrogen atom of the carboxamide group bound to hydrogen atoms or to acyclic carbon atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Engineering & Computer Science (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pulmonology (AREA)
- Immunology (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)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Other In-Based Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Cephalosporin Compounds (AREA)
- Pyridine Compounds (AREA)
- Compositions Of Macromolecular Compounds (AREA)
Applications Claiming Priority (6)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US34893001P | 2001-10-26 | 2001-10-26 | |
| US348930P | 2001-10-26 | ||
| US36197902P | 2002-03-06 | 2002-03-06 | |
| US361979P | 2002-03-06 | ||
| US39152102P | 2002-06-25 | 2002-06-25 | |
| US391521P | 2002-06-25 |
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| ES2315425T3 true ES2315425T3 (es) | 2009-04-01 |
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| ES02793840T Expired - Lifetime ES2315425T3 (es) | 2001-10-26 | 2002-10-25 | Compuestos de amonio cuaternario y su uso como agentes antimuscarinicos. |
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| BR (1) | BR0206207A (https=) |
| CA (1) | CA2464223C (https=) |
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| MX (1) | MXPA04003865A (https=) |
| MY (1) | MY130316A (https=) |
| NO (1) | NO20032938L (https=) |
| PT (1) | PT1461306E (https=) |
| SG (1) | SG168451A1 (https=) |
| WO (1) | WO2003035599A1 (https=) |
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| EP0957073A1 (en) | 1998-05-12 | 1999-11-17 | Schwarz Pharma Ag | Novel derivatives of 3,3-diphenylpropylamines |
| DE60230546D1 (de) * | 2001-10-26 | 2009-02-05 | Pharmacia & Upjohn Co Llc | Quaternäre ammoniumverbindungen und deren verwendung als antimuscarinische wirkstoffe |
| US7754242B2 (en) * | 2002-03-20 | 2010-07-13 | Alkermes, Inc. | Inhalable sustained therapeutic formulations |
| AU2003231777C1 (en) * | 2002-04-29 | 2009-10-29 | Supernus Pharmaceuticals, Inc. | Pharmaceutical formulations with improved bioavailability |
| DE10315917A1 (de) * | 2003-04-08 | 2004-11-18 | Schwarz Pharma Ag | Hochreine Basen von 3,3-Diphenylpropylaminmonoestern |
| JP2006523676A (ja) * | 2003-04-15 | 2006-10-19 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | 第四級アンモニウム化合物と、その抗ムスカリン性剤としての使用 |
| WO2004091597A2 (en) * | 2003-04-15 | 2004-10-28 | Pharmacia & Upjohn Company Llc | Method of treating irritable bowel syndrome (ibs) |
| JP2006523674A (ja) * | 2003-04-18 | 2006-10-19 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | 慢性閉塞性肺疾患(copd)のための組合せ治療法 |
| WO2004096751A1 (en) * | 2003-04-25 | 2004-11-11 | Pharmacia & Upjohn Company Llc | Halogen substituted 3,3-diphenylpropylamines (tolterodine) having antimuscarinic activity |
| DK2210605T3 (en) * | 2003-11-04 | 2017-05-22 | Tcd Royalty Sub Llc | Daily single dose doses of trospium. |
| US8709476B2 (en) | 2003-11-04 | 2014-04-29 | Supernus Pharmaceuticals, Inc. | Compositions of quaternary ammonium compounds containing bioavailability enhancers |
| ES2235648B1 (es) * | 2003-12-22 | 2006-11-01 | Ragactives, S.L. | Procedimiento para la obtencion de tolterodina. |
| EP1701932B1 (en) * | 2003-12-24 | 2012-07-18 | Cipla Ltd. | Tolterodine, compositions and uses thereof, and preparation of the same |
| JP2007530451A (ja) * | 2004-03-11 | 2007-11-01 | グラクソ グループ リミテッド | 新規m3ムスカリン性アセチルコリン受容体アンタゴニスト |
| EP1838659B1 (en) * | 2004-12-24 | 2015-07-15 | LEK Pharmaceuticals d.d. | Process for preparation of n,n-diisopropyl-3-(2-hydroxy-5-methylphenyl)-3-phenylpropylamine |
| US20110135580A1 (en) * | 2006-05-24 | 2011-06-09 | Boehringer Ingelheim International Gmbh | Novel Medicament Combinations for the Treatment of Respiratory Diseases |
| EP1908502A1 (en) * | 2006-10-02 | 2008-04-09 | Koninklijke Philips Electronics N.V. | Interactive modular tile system |
| US7731604B2 (en) * | 2006-10-31 | 2010-06-08 | Taylor Made Golf Company, Inc. | Golf club iron head |
| US20100112061A1 (en) * | 2006-12-13 | 2010-05-06 | William Baker | Monophosphates as Mutual Prodrugs of Muscarinic Receptor Antagonists and Beta-Agonists for the Treatment of COPD And Chronic Bronchitis |
| ES2554646T3 (es) * | 2007-02-23 | 2015-12-22 | Theravance Biopharma R&D Ip, Llc | Compuestos de difenilmetilo de amonio cuaternario, de utilidad como antagonistas de receptores muscarínicos |
| CA2682032A1 (en) | 2007-04-24 | 2008-11-06 | Theravance, Inc. | Quaternary ammonium compounds useful as muscarinic receptor antagonists |
| US20090246146A1 (en) * | 2008-01-25 | 2009-10-01 | Botond Banfi | Halides in the treatment of pathogenic infection |
| US20090318396A1 (en) * | 2008-06-10 | 2009-12-24 | Gilead Sciences, Inc. | Corticosteroid linked beta-agonist compounds for use in therapy |
| WO2010010464A2 (en) * | 2008-07-21 | 2010-01-28 | Actavis Group Ptc Ehf | Fesoterodine substantially free of dehydroxy impurity |
| JP5801997B2 (ja) | 2009-07-07 | 2015-10-28 | ファイザー・リミテッドPfizer Limited | 薬品の組合せを吸入するための投薬ユニット、投薬ユニットのパック、および吸入器 |
| CN110372571B (zh) * | 2018-04-12 | 2022-11-15 | 中国科学院大连化学物理研究所 | 一种2-(2,2-二芳基乙基)-环胺衍生物或盐及合成和应用与组合物 |
| CN110845357B (zh) * | 2019-11-22 | 2022-09-30 | 华东理工大学 | 季铵盐型酰肼化合物及由其制备的季铵盐型腙类化合物与应用 |
| CN116033893A (zh) | 2020-06-26 | 2023-04-28 | 迈兰制药英国有限公司 | 包含5-[3-(3-羟基苯氧基)氮杂环丁烷-1-基]-5-甲基-2,2-二苯基己酰胺的制剂 |
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| US2592191A (en) * | 1949-09-16 | 1952-04-08 | Sterling Drug Inc | Quaternary ammonium salts of nu-(3, 3-diphenylpropyl) pyrrolidine |
| NL267508A (https=) | 1960-07-26 | |||
| NL6717123A (https=) | 1966-12-29 | 1968-07-01 | ||
| US3505337A (en) | 1967-12-22 | 1970-04-07 | Boehringer Sohn Ingelheim | N - hydrocarbyl-substituted noratropinium,haloalkylates and o-acyl derivatives thereof |
| US5382600A (en) | 1988-01-22 | 1995-01-17 | Pharmacia Aktiebolag | 3,3-diphenylpropylamines and pharmaceutical compositions thereof |
| IL91377A (en) | 1988-09-14 | 1996-09-12 | Nippon Shinyaku Co Ltd | Derivatives of botinylamine glycolate |
| GB8906166D0 (en) | 1989-03-17 | 1989-05-04 | Pfizer Ltd | Therapeutic agents |
| DE3931041C2 (de) | 1989-09-16 | 2000-04-06 | Boehringer Ingelheim Kg | Ester von Thienylcarbonsäuren mit Aminoalkoholen, ihre Quaternierungsprodukte, Verfahren zu ihrer Herstellung und diese enthaltende Arzneimittel |
| SE9203318D0 (sv) | 1992-11-06 | 1992-11-06 | Kabi Pharmacia Ab | Novel 3,3-diphenylpropylamines, their use and preparation |
| US5492933A (en) | 1993-10-08 | 1996-02-20 | Sepracor, Inc. | Methods and compositions for treating urinary incontinence and other disorders using optically pure R-terodiline and hydroxylated derivatives thereof |
| AU7971394A (en) | 1993-10-08 | 1995-05-04 | Sepracor, Inc. | Method for treating urinary incontinence using optically pure s-terodiline |
| KR20000057548A (ko) | 1996-12-13 | 2000-09-25 | 알프레드 엘. 미첼슨 | 광학적 전송물질 및 결합재 |
| SE9701144D0 (sv) * | 1997-03-27 | 1997-03-27 | Pharmacia & Upjohn Ab | Novel compounds, their use and preparation |
| PE20020547A1 (es) * | 2000-10-24 | 2002-06-12 | Upjohn Co | Uso de la tolterodina en tratamientos del asma |
| WO2002035245A1 (en) | 2000-10-26 | 2002-05-02 | Koninklijke Philips Electronics N.V. | Electronic device |
| DE60230546D1 (de) * | 2001-10-26 | 2009-02-05 | Pharmacia & Upjohn Co Llc | Quaternäre ammoniumverbindungen und deren verwendung als antimuscarinische wirkstoffe |
| JP2006523676A (ja) * | 2003-04-15 | 2006-10-19 | ファルマシア・アンド・アップジョン・カンパニー・エルエルシー | 第四級アンモニウム化合物と、その抗ムスカリン性剤としての使用 |
| WO2004096751A1 (en) * | 2003-04-25 | 2004-11-11 | Pharmacia & Upjohn Company Llc | Halogen substituted 3,3-diphenylpropylamines (tolterodine) having antimuscarinic activity |
-
2002
- 2002-10-25 DE DE60230546T patent/DE60230546D1/de not_active Expired - Lifetime
- 2002-10-25 ES ES02793840T patent/ES2315425T3/es not_active Expired - Lifetime
- 2002-10-25 PT PT02793840T patent/PT1461306E/pt unknown
- 2002-10-25 CA CA002464223A patent/CA2464223C/en not_active Expired - Fee Related
- 2002-10-25 AT AT02793840T patent/ATE418534T1/de active
- 2002-10-25 JP JP2003538115A patent/JP3981357B2/ja not_active Expired - Fee Related
- 2002-10-25 BR BR0206207-0A patent/BR0206207A/pt not_active Application Discontinuation
- 2002-10-25 DK DK02793840T patent/DK1461306T3/da active
- 2002-10-25 MY MYPI20024003A patent/MY130316A/en unknown
- 2002-10-25 US US10/280,906 patent/US6890920B2/en not_active Expired - Fee Related
- 2002-10-25 MX MXPA04003865A patent/MXPA04003865A/es active IP Right Grant
- 2002-10-25 WO PCT/US2002/034529 patent/WO2003035599A1/en not_active Ceased
- 2002-10-25 SG SG200905309-1A patent/SG168451A1/en unknown
- 2002-10-25 EP EP02793840A patent/EP1461306B1/en not_active Expired - Lifetime
-
2003
- 2003-06-26 NO NO20032938A patent/NO20032938L/no not_active Application Discontinuation
-
2005
- 2005-03-08 US US11/074,914 patent/US7439397B2/en not_active Expired - Fee Related
-
2009
- 2009-02-03 CY CY20091100122T patent/CY1109898T1/el unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003035599A1 (en) | 2003-05-01 |
| EP1461306B1 (en) | 2008-12-24 |
| CA2464223C (en) | 2009-05-26 |
| NO20032938D0 (no) | 2003-06-26 |
| JP3981357B2 (ja) | 2007-09-26 |
| NO20032938L (no) | 2003-08-25 |
| PT1461306E (pt) | 2009-04-01 |
| CA2464223A1 (en) | 2003-05-01 |
| ATE418534T1 (de) | 2009-01-15 |
| MXPA04003865A (es) | 2004-07-08 |
| US7439397B2 (en) | 2008-10-21 |
| JP2005524605A (ja) | 2005-08-18 |
| BR0206207A (pt) | 2003-12-23 |
| DK1461306T3 (da) | 2009-03-09 |
| MY130316A (en) | 2007-06-29 |
| CY1109898T1 (el) | 2014-09-10 |
| US20030158176A1 (en) | 2003-08-21 |
| US20050148672A1 (en) | 2005-07-07 |
| US6890920B2 (en) | 2005-05-10 |
| SG168451A1 (en) | 2011-02-28 |
| DE60230546D1 (de) | 2009-02-05 |
| EP1461306A1 (en) | 2004-09-29 |
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