MX2015007279A - Nuevos derivados carbamato de ciclohexilo y quinuclidinilo que tienen actividad como agonistas b2 adrenergicos y como antagonistas muscarinicos m3. - Google Patents
Nuevos derivados carbamato de ciclohexilo y quinuclidinilo que tienen actividad como agonistas b2 adrenergicos y como antagonistas muscarinicos m3.Info
- Publication number
- MX2015007279A MX2015007279A MX2015007279A MX2015007279A MX2015007279A MX 2015007279 A MX2015007279 A MX 2015007279A MX 2015007279 A MX2015007279 A MX 2015007279A MX 2015007279 A MX2015007279 A MX 2015007279A MX 2015007279 A MX2015007279 A MX 2015007279A
- Authority
- MX
- Mexico
- Prior art keywords
- group
- hydroxy
- amino
- oxo
- ethyl
- Prior art date
Links
- 239000003149 muscarinic antagonist Substances 0.000 title claims abstract description 9
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 title claims abstract description 8
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 title claims description 39
- 230000000694 effects Effects 0.000 title claims description 19
- 239000000048 adrenergic agonist Substances 0.000 title abstract description 6
- LSUSEBREYXZDHC-UHFFFAOYSA-N 1-azabicyclo[2.2.2]octan-2-yl carbamate Chemical class C1CN2C(OC(=O)N)CC1CC2 LSUSEBREYXZDHC-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 164
- 238000000034 method Methods 0.000 claims abstract description 36
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 10
- -1 3-bromoisoxazol-5-yl Chemical group 0.000 claims description 721
- 125000006269 biphenyl-2-yl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C1=C(*)C([H])=C([H])C([H])=C1[H] 0.000 claims description 291
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 276
- KXDHJXZQYSOELW-UHFFFAOYSA-M Carbamate Chemical compound NC([O-])=O KXDHJXZQYSOELW-UHFFFAOYSA-M 0.000 claims description 236
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 171
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 123
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 111
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 90
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 77
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 73
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 69
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 66
- 150000003839 salts Chemical class 0.000 claims description 56
- KXDHJXZQYSOELW-UHFFFAOYSA-N carbonic acid monoamide Natural products NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 52
- KJAMZCVTJDTESW-UHFFFAOYSA-N tiracizine Chemical compound C1CC2=CC=CC=C2N(C(=O)CN(C)C)C2=CC(NC(=O)OCC)=CC=C21 KJAMZCVTJDTESW-UHFFFAOYSA-N 0.000 claims description 51
- 229910052757 nitrogen Inorganic materials 0.000 claims description 41
- VDAXSUWCLDAOTF-IZLXSQMJSA-N C(N)(O[C@@H]1CC[C@H](CC1)N)=O Chemical compound C(N)(O[C@@H]1CC[C@H](CC1)N)=O VDAXSUWCLDAOTF-IZLXSQMJSA-N 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 36
- 125000005843 halogen group Chemical group 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 35
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 32
- 125000002619 bicyclic group Chemical group 0.000 claims description 32
- 125000005842 heteroatom Chemical group 0.000 claims description 32
- 125000002950 monocyclic group Chemical group 0.000 claims description 32
- 229910052760 oxygen Inorganic materials 0.000 claims description 31
- 229910052717 sulfur Inorganic materials 0.000 claims description 31
- 125000000217 alkyl group Chemical group 0.000 claims description 28
- 125000003545 alkoxy group Chemical group 0.000 claims description 25
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
- 201000010099 disease Diseases 0.000 claims description 23
- 238000011282 treatment Methods 0.000 claims description 23
- 125000004432 carbon atom Chemical group C* 0.000 claims description 22
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 22
- 229920006395 saturated elastomer Polymers 0.000 claims description 22
- 125000004122 cyclic group Chemical group 0.000 claims description 21
- 230000002969 morbid Effects 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 15
- RAJYWSMRWRODFV-ZETCQYMHSA-N [(3R)-1-azabicyclo[2.2.2]octan-3-yl] carbamate Chemical compound N12C[C@@H](C(CC1)CC2)OC(N)=O RAJYWSMRWRODFV-ZETCQYMHSA-N 0.000 claims description 14
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 14
- 229910052739 hydrogen Inorganic materials 0.000 claims description 14
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 14
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 14
- 125000002947 alkylene group Chemical group 0.000 claims description 13
- 208000006673 asthma Diseases 0.000 claims description 13
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 13
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 12
- 229910052801 chlorine Inorganic materials 0.000 claims description 12
- 125000001072 heteroaryl group Chemical group 0.000 claims description 12
- 125000004043 oxo group Chemical group O=* 0.000 claims description 12
- 150000001412 amines Chemical class 0.000 claims description 11
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 11
- 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 10
- 108060003345 Adrenergic Receptor Proteins 0.000 claims description 10
- 102000017910 Adrenergic receptor Human genes 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 10
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 10
- 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 9
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
- 208000019693 Lung disease Diseases 0.000 claims description 8
- 239000002253 acid Substances 0.000 claims description 8
- 125000004450 alkenylene group Chemical group 0.000 claims description 8
- 125000004429 atom Chemical group 0.000 claims description 8
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 208000020446 Cardiac disease Diseases 0.000 claims description 7
- 208000010412 Glaucoma Diseases 0.000 claims description 7
- 206010061218 Inflammation Diseases 0.000 claims description 7
- 208000012902 Nervous system disease Diseases 0.000 claims description 7
- 125000004419 alkynylene group Chemical group 0.000 claims description 7
- 239000000460 chlorine Substances 0.000 claims description 7
- 208000019622 heart disease Diseases 0.000 claims description 7
- 125000000623 heterocyclic group Chemical group 0.000 claims description 7
- 230000004054 inflammatory process Effects 0.000 claims description 7
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 7
- VDAXSUWCLDAOTF-UHFFFAOYSA-N (4-aminocyclohexyl) carbamate Chemical compound NC1CCC(OC(N)=O)CC1 VDAXSUWCLDAOTF-UHFFFAOYSA-N 0.000 claims description 6
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 6
- 208000018522 Gastrointestinal disease Diseases 0.000 claims description 6
- 241001465754 Metazoa Species 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 6
- 125000004076 pyridyl group Chemical group 0.000 claims description 6
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 5
- 229940123932 Phosphodiesterase 4 inhibitor Drugs 0.000 claims description 5
- 208000005107 Premature Birth Diseases 0.000 claims description 5
- 206010036590 Premature baby Diseases 0.000 claims description 5
- 230000027455 binding Effects 0.000 claims description 5
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 239000003246 corticosteroid Substances 0.000 claims description 5
- 125000005647 linker group Chemical group 0.000 claims description 5
- 239000002587 phosphodiesterase IV inhibitor Substances 0.000 claims description 5
- 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims description 4
- 208000025966 Neurological disease Diseases 0.000 claims description 4
- 125000003277 amino group Chemical group 0.000 claims description 4
- 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 claims description 4
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 3
- 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 3
- 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 3
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052720 vanadium Inorganic materials 0.000 claims description 3
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 2
- 125000006201 3-phenylpropyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
- 239000013066 combination product Substances 0.000 claims description 2
- 229940127555 combination product Drugs 0.000 claims description 2
- 239000003085 diluting agent Substances 0.000 claims description 2
- 125000004494 ethyl ester group Chemical group 0.000 claims description 2
- 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 2
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 2
- 229910052702 rhenium Inorganic materials 0.000 claims description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 claims 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims 1
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims 1
- 229940121786 Beta 2 adrenoreceptor agonist Drugs 0.000 claims 1
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims 1
- 101100456896 Drosophila melanogaster metl gene Proteins 0.000 claims 1
- 239000000556 agonist Substances 0.000 claims 1
- 125000003368 amide group Chemical group 0.000 claims 1
- 230000001575 pathological effect Effects 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 38
- 230000008569 process Effects 0.000 abstract description 6
- 230000009977 dual effect Effects 0.000 abstract description 3
- 238000002644 respiratory therapy Methods 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 description 593
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 247
- 239000012043 crude product Substances 0.000 description 192
- 239000000203 mixture Substances 0.000 description 173
- 238000002474 experimental method Methods 0.000 description 170
- 239000007787 solid Substances 0.000 description 164
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 153
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 128
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 121
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 114
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 113
- 238000004440 column chromatography Methods 0.000 description 105
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 102
- 239000000741 silica gel Substances 0.000 description 99
- 229910002027 silica gel Inorganic materials 0.000 description 99
- 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 84
- 239000002904 solvent Substances 0.000 description 80
- 239000000243 solution Substances 0.000 description 77
- 238000000746 purification Methods 0.000 description 74
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 71
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 68
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 66
- 230000002829 reductive effect Effects 0.000 description 64
- 125000004973 1-butenyl group Chemical group C(=CCC)* 0.000 description 59
- 229910021529 ammonia Inorganic materials 0.000 description 57
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 51
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- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 39
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- VACIHIUOJBHCEK-UHFFFAOYSA-N C1=CC=C(C=C1)C2=C(C(=CC=C2)Br)OC(=O)N Chemical compound C1=CC=C(C=C1)C2=C(C(=CC=C2)Br)OC(=O)N VACIHIUOJBHCEK-UHFFFAOYSA-N 0.000 description 37
- IKGLACJFEHSFNN-UHFFFAOYSA-N hydron;triethylazanium;trifluoride Chemical compound F.F.F.CCN(CC)CC IKGLACJFEHSFNN-UHFFFAOYSA-N 0.000 description 37
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 36
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- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 34
- YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 34
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 32
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 32
- COIOYMYWGDAQPM-UHFFFAOYSA-N tris(2-methylphenyl)phosphane Chemical compound CC1=CC=CC=C1P(C=1C(=CC=CC=1)C)C1=CC=CC=C1C COIOYMYWGDAQPM-UHFFFAOYSA-N 0.000 description 32
- 239000012321 sodium triacetoxyborohydride Substances 0.000 description 30
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 26
- 125000006238 prop-1-en-1-yl group Chemical group [H]\C(*)=C(/[H])C([H])([H])[H] 0.000 description 26
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 25
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 24
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- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 7
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
- 238000003756 stirring Methods 0.000 description 7
- ADZUEEUKBYCSEY-UHFFFAOYSA-N 1h-indole-5-carbaldehyde Chemical compound O=CC1=CC=C2NC=CC2=C1 ADZUEEUKBYCSEY-UHFFFAOYSA-N 0.000 description 6
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 6
- DOBRDRYODQBAMW-UHFFFAOYSA-N copper(i) cyanide Chemical compound [Cu+].N#[C-] DOBRDRYODQBAMW-UHFFFAOYSA-N 0.000 description 6
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- FJDQFPXHSGXQBY-UHFFFAOYSA-L caesium carbonate Chemical compound [Cs+].[Cs+].[O-]C([O-])=O FJDQFPXHSGXQBY-UHFFFAOYSA-L 0.000 description 1
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- XTMWVLWAAVBHML-UHFFFAOYSA-N methyl 3-amino-4-hydroxybenzoate;hydrochloride Chemical compound Cl.COC(=O)C1=CC=C(O)C(N)=C1 XTMWVLWAAVBHML-UHFFFAOYSA-N 0.000 description 1
- OCZXDVNSNDITBS-UHFFFAOYSA-N methyl 4-amino-3-hydroxybenzoate Chemical compound COC(=O)C1=CC=C(N)C(O)=C1 OCZXDVNSNDITBS-UHFFFAOYSA-N 0.000 description 1
- MHNNAWXXUZQSNM-UHFFFAOYSA-N methylethylethylene Natural products CCC(C)=C MHNNAWXXUZQSNM-UHFFFAOYSA-N 0.000 description 1
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- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
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- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
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- LCELQERNWLBPSY-KHSTUMNDSA-M oxitropium bromide Chemical compound [Br-].C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)CC)=CC=CC=C1 LCELQERNWLBPSY-KHSTUMNDSA-M 0.000 description 1
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- HVAMZGADVCBITI-UHFFFAOYSA-M pent-4-enoate Chemical compound [O-]C(=O)CCC=C HVAMZGADVCBITI-UHFFFAOYSA-M 0.000 description 1
- KHIWWQKSHDUIBK-UHFFFAOYSA-N periodic acid Chemical compound OI(=O)(=O)=O KHIWWQKSHDUIBK-UHFFFAOYSA-N 0.000 description 1
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- MFDFERRIHVXMIY-UHFFFAOYSA-N procaine Chemical compound CCN(CC)CCOC(=O)C1=CC=C(N)C=C1 MFDFERRIHVXMIY-UHFFFAOYSA-N 0.000 description 1
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- 125000001422 pyrrolinyl group Chemical group 0.000 description 1
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- 125000002294 quinazolinyl group Chemical group N1=C(N=CC2=CC=CC=C12)* 0.000 description 1
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- 125000001567 quinoxalinyl group Chemical group N1=C(C=NC2=CC=CC=C12)* 0.000 description 1
- SUXJMLFJAQJBRU-UHFFFAOYSA-N quinuclidinyl Chemical class C1[C-](CC2)CC[N+]2=C1 SUXJMLFJAQJBRU-UHFFFAOYSA-N 0.000 description 1
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- 239000012279 sodium borohydride Substances 0.000 description 1
- 229910000033 sodium borohydride Inorganic materials 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 238000004611 spectroscopical analysis Methods 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
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- FEYLUKDSKVSMSZ-UHFFFAOYSA-N tert-butyl n-(4-aminocyclohexyl)carbamate Chemical compound CC(C)(C)OC(=O)NC1CCC(N)CC1 FEYLUKDSKVSMSZ-UHFFFAOYSA-N 0.000 description 1
- FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 1
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- 125000003507 tetrahydrothiofenyl group Chemical group 0.000 description 1
- 125000004632 tetrahydrothiopyranyl group Chemical group S1C(CCCC1)* 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 229960004559 theobromine Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 125000000335 thiazolyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 210000001519 tissue Anatomy 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
- 230000009466 transformation Effects 0.000 description 1
- YFTHZRPMJXBUME-UHFFFAOYSA-N tripropylamine Chemical compound CCCN(CCC)CCC YFTHZRPMJXBUME-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 231100000397 ulcer Toxicity 0.000 description 1
- JOYRKODLDBILNP-UHFFFAOYSA-N urethane group Chemical group NC(=O)OCC JOYRKODLDBILNP-UHFFFAOYSA-N 0.000 description 1
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- XPARCVGSTPKNNR-UHFFFAOYSA-M zinc;ethyl butanoate;bromide Chemical compound [Zn+2].[Br-].CCOC(=O)CC[CH2-] XPARCVGSTPKNNR-UHFFFAOYSA-M 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D453/00—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids
- C07D453/02—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems
- C07D453/04—Heterocyclic compounds containing quinuclidine or iso-quinuclidine ring systems, e.g. quinine alkaloids containing not further condensed quinuclidine ring systems having a quinolyl-4, a substituted quinolyl-4 or a alkylenedioxy-quinolyl-4 radical linked through only one carbon atom, attached in position 2, e.g. quinine
-
- 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
- A61K31/13—Amines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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| EA201500651A1 (ru) | 2012-12-18 | 2015-11-30 | Альмираль, С.А. | НОВЫЕ ПРОИЗВОДНЫЕ ЦИКЛОГЕКСИЛ- И ХИНУКЛИДИНИЛКАРБАМАТА, ОБЛАДАЮЩИЕ АГОНИСТИЧЕСКОЙ АКТИВНОСТЬЮ ПО ОТНОШЕНИЮ К β2 АДРЕНЕРГИЧЕСКОМУ РЕЦЕПТОРУ И АНТАГОНИСТИЧЕСКОЙ АКТИВНОСТЬЮ ПО ОТНОШЕНИЮ К МУСКАРИНОВОМУ РЕЦЕПТОРУ М3 |
| TWI643853B (zh) | 2013-02-27 | 2018-12-11 | 阿爾米雷爾有限公司 | 同時具有β2腎上腺素受體促效劑和M3毒蕈鹼受體拮抗劑活性之2-氨基-1-羥乙基-8-羥基喹啉-2(1H)-酮衍生物之鹽類 |
| TWI641373B (zh) | 2013-07-25 | 2018-11-21 | 阿爾米雷爾有限公司 | 具有蕈毒鹼受體拮抗劑和β2腎上腺素受體促效劑二者之活性的2-胺基-1-羥乙基-8-羥基喹啉-2(1H)-酮衍生物之鹽 |
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| ATE25966T1 (de) | 1983-09-26 | 1987-04-15 | Magis Farmaceutici | Aminocyclohexanol-derivate mit expektoranter wirkung, verfahren zu deren herstellung und diese enthaltende pharmazeutische zusammensetzungen. |
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| DE19536902A1 (de) | 1995-10-04 | 1997-04-10 | Boehringer Ingelheim Int | Vorrichtung zur Hochdruckerzeugung in einem Fluid in Miniaturausführung |
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